Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Chemotherapy and Unrelated Donor Stem Cell Transplantation for Patients With Cancers of the Blood and Immune System

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00520130
Recruitment Status : Completed
First Posted : August 23, 2007
Results First Posted : August 24, 2017
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
Steven Pavletic, M.D., National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Myelodysplastic Syndrome
Hodgkin's Lymphoma
Non-Hodgkin's Disease
Acute Leukemia
Multiple Myeloma
Interventions Biological: Rituximab
Drug: Cyclosporine
Drug: Allogenic stem cell transplant (ASCT)
Drug: Conditioning Chemotherapy
Drug: TMS
Drug: FLAG
Drug: EPOCH-F
Biological: Alemtuzumab
Enrollment 92
Recruitment Details  
Pre-assignment Details There were 89 participants in the study. 3 patients enrolled and their cancers progressed prior to randomization so they were taken off study. 3 of these participants went back into remission with additional chemo and were re-enrolled on the protocol and randomized. They are counted twice in the enrolment (e.g. 92) but only once in the Started row.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description Rituximab: 375 mg/m2 intravenous (IV), day 1 for patients (pts) with cluster of differentiation 20-positive disease. Allogenic stem cell transplant (txplt). Fludarabine:30 mg/m2 per day IV over 30 min. daily. On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV over 2 hrs on Days 6, -5, -4, -3. Mesna:1200 mg/m2 per day IV, Daily on days 6, -5,-4, and -3.Tacrolimus: day -3 before txplt, 0.02 mg/kg/day CIV, then switch to an equivalent oral dose (when pts taking po) titrated for a goal level of 5-10 ng/ml; Sirolimus: loading dose of 12 mg p.o. on day -3 pre-txplt, 4 mg day -2 pre-txplt and titrated for levels 3-12 ng/ml; Methotrexate 5 mg/m2 IV on days +1, +3, +6, and +11 post txplt). Tacrolimus and sirolimus will be tapered at day +63, day +119 and day +180 post-txplt as tolerated. Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5.Cytarabine: 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hrs before chemo. Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Period Title: Overall Study
Started 44 45
Completed 39 44
Not Completed 5 1
Reason Not Completed
Disease progression on study             4             0
Physician Decision             1             1
Arm/Group Title Tacrolimus, Methotrexate, Sirolimus (TMS) Arm Cyclosporine (AC) Arm Total
Hide Arm/Group Description Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months. Total of all reporting groups
Overall Number of Baseline Participants 44 45 89
Hide Baseline Analysis Population Description
There were 89 participants in the study. 3 patients enrolled and their cancers progressed prior to randomization so they were taken off study. 3 of these participants went back into remission with additional chemo and were re-enrolled on the protocol and randomized. They are counted twice in the enrolment (e.g. 92) but only once in the Started row.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 45 participants 89 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
38
  86.4%
41
  91.1%
79
  88.8%
>=65 years
6
  13.6%
4
   8.9%
10
  11.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 44 participants 45 participants 89 participants
47.92  (14.68) 47.89  (13.4) 47.90  (14.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 45 participants 89 participants
Female
16
  36.4%
15
  33.3%
31
  34.8%
Male
28
  63.6%
30
  66.7%
58
  65.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 45 participants 89 participants
Hispanic or Latino
2
   4.5%
2
   4.4%
4
   4.5%
Not Hispanic or Latino
42
  95.5%
43
  95.6%
85
  95.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 45 participants 89 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
   6.8%
1
   2.2%
4
   4.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   6.8%
4
   8.9%
7
   7.9%
White
38
  86.4%
39
  86.7%
77
  86.5%
More than one race
0
   0.0%
1
   2.2%
1
   1.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 44 participants 45 participants 89 participants
44
 100.0%
45
 100.0%
89
 100.0%
Histology   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 45 participants 89 participants
Non Hodgkin's Lymphoma (NHL) 11 14 25
Hodgkin's Lymphoma (HL) 5 5 10
Chroni Lymphocytic Leukemia (CLL) 9 9 18
AML/MDS 6 5 11
Chronic Myeloid Leukemia (CML) 4 1 5
CTCL/PTCL 3 2 5
Acute Lymphoblastic Leukemia (ALL) 2 2 4
Multiple Myeloma (MM) 1 1 2
Other 3 6 9
[1]
Measure Description: Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS); Cutaneous T Cell Lymphoma (CTCL)/Peripheral T Cell Lymphoma (PTCL)
1.Primary Outcome
Title Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD)
Hide Description Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 39 42
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
42
(26 to 57)
38
(23 to 53)
2.Primary Outcome
Title Percentage of Participants With Chronic Graft Versus Host Disease (cGVHD)
Hide Description Chronic GVHD is assessed by the 2005 Chronic GVHD Consensus Project. First the individual organ scoring is done, and then based on that the Global score is determined (mild-moderate-severe). See Citation: Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11:945-56., for grading criteria.
Time Frame 2 years post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 39 42
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Moderate or Severe cGVHD
50
(32 to 65)
12
(4 to 25)
Severe cGVHD
28
(14 to 43)
5
(1 to 15)
3.Primary Outcome
Title Recovery of Naïve Cluster of Differentiation 4 (CD4) T Cells
Hide Description The percentage of C-C motif chemokine receptor 7 (CCR7)+CD45RA+ naïve T cells within the CD4 T cell populations was determined by flow cytometry.
Time Frame Recipient recovery at 6, 12 and 24 months post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
A few measurements were missed, one patient was not evaluable for technical reasons and removed from the analysis, but most of the decline was due to patients that had gone off study.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 28 28
Median (Full Range)
Unit of Measure: % of naive (CCR7+CD45RA+) CD4 Cells
6 mo (TMS=28; AC= 28)
24
(2 to 65)
1
(0 to 22)
12 mo (TMS=25; AC= 21)
22
(5 to 48)
7
(0 to 42)
24 mo (TMS=18; AC= 13)
20
(4 to 60)
25
(1 to 60)
4.Primary Outcome
Title Recovery of Naïve Cluster of Differentiation 8 (CD8) T Cells
Hide Description The percentage of CCR7+CD45RA+ naïve T cells within the CD4 and CD8 T cell populations was determined by flow cytometry.
Time Frame Recipient recovery at 6, 12 and 24 months post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
A few measurements were missed, one patient was not evaluable for technical reasons and removed from the analysis, but most of the decline was due to patients that had gone off study.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 28 28
Median (Full Range)
Unit of Measure: % of naive (CCR7+CD45RA+) CD8 Cells
6 mo (TMS=28; AC= 28)
20
(0 to 75)
3
(0 to 78)
12 mo (TMS=25; AC= 21)
17
(7 to 79)
6
(0 to 79)
24 mo (TMS=18; AC= 13)
16
(1 to 60)
6
(0 to 65)
5.Primary Outcome
Title Changes in Cluster of Differentiation 4 (CD4) T Cell Receptor Vbeta Repertoire
Hide Description Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient’s T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison.
Time Frame Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
The original intention was to perform these assays on the first 10 pts within each arm. One pt died within the first mo., others died within the 1st yr. Not all donors gave consent for research analyses to be done on their cells, hence cells from those donors were not available.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:
Rituximab: 375 mg/m2 intravenous (IV), day 1 for patients (pts) with cluster of differentiation 20-positive disease. Allogenic stem cell transplant (txplt). Fludarabine:30 mg/m2 per day IV over 30 min. daily. On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV over 2 hrs on Days 6, -5, -4, -3. Mesna:1200 mg/m2 per day IV, Daily on days 6, -5,-4, and -3.Tacrolimus: day -3 before txplt, 0.02 mg/kg/day CIV, then switch to an equivalent oral dose (when pts taking po) titrated for a goal level of 5-10 ng/ml; Sirolimus: loading dose of 12 mg p.o. on day -3 pre-txplt, 4 mg day -2 pre-txplt and titrated for levels 3-12 ng/ml; Methotrexate 5 mg/m2 IV on days +1, +3, +6, and +11 post txplt). Tacrolimus and sirolimus will be tapered at day +63, day +119 and day +180 post-txplt as tolerated. Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5.Cytarabine: 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hrs before chemo.
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: Divergence index
1 month
48
(26 to 69)
90
(63 to 111)
3 months
31
(23 to 60)
66
(47 to 93)
6 mo (TMS=7; AC= 9)
35
(21 to 57)
75
(32 to 93)
12 mo (TMS=7; AC=9)
30
(23 to 81)
67
(25 to 92)
Donor CD4 cells (TMS=8; AC=8)
23
(17 to 29)
22
(18 to 35)
6.Primary Outcome
Title Changes in CD8 T Cell Receptor Vbeta Repertoire
Hide Description Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient’s T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison.
Time Frame Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
The original intention was to perform these assays on the first 10 pts within each arm. One pt died within the first mo., others died within the 1st yr. Not all donors gave consent for research analyses to be done on their cells, hence cells from those donors were not available.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:
Rituximab: 375 mg/m2 intravenous (IV), day 1 for patients (pts) with cluster of differentiation 20-positive disease. Allogenic stem cell transplant (txplt). Fludarabine:30 mg/m2 per day IV over 30 min. daily. On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV over 2 hrs on Days 6, -5, -4, -3. Mesna:1200 mg/m2 per day IV, Daily on days 6, -5,-4, and -3.Tacrolimus: day -3 before txplt, 0.02 mg/kg/day CIV, then switch to an equivalent oral dose (when pts taking po) titrated for a goal level of 5-10 ng/ml; Sirolimus: loading dose of 12 mg p.o. on day -3 pre-txplt, 4 mg day -2 pre-txplt and titrated for levels 3-12 ng/ml; Methotrexate 5 mg/m2 IV on days +1, +3, +6, and +11 post txplt). Tacrolimus and sirolimus will be tapered at day +63, day +119 and day +180 post-txplt as tolerated. Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5.Cytarabine: 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hrs before chemo.
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: Divergence index
1 month
62
(42 to 91)
78
(53 to 111)
3 months
54
(35 to 64)
81
(52 to 88)
6 mo (TMS=7; AC= 9)
62
(53 to 81)
84
(71 to 118)
12 mo (TMS=7; AC= 9)
55
(39 to 108)
89
(58 to 110)
Donor CD8 cells (TMS=8; AC= 8)
47
(27 to 53)
43
(31 to 62)
7.Secondary Outcome
Title Percentage of Participants With Grade III-IV Acute Graft Versus Host Disease (GVHD)
Hide Description Acute GVHD is assessed by the 1994 Consensus Conference on acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 39 42
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13
(5 to 26)
21
(11 to 35)
8.Secondary Outcome
Title Toxicities
Hide Description Here are the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame 103 months and 22 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 44 45
Measure Type: Number
Unit of Measure: participants
43 42
9.Secondary Outcome
Title Days to Engraftment of Neutrophils
Hide Description Days to engraftment is defined as neutrophil recovery: designated by the first of 3 consecutive days with an absolute neutrophil count (ANC) above 500/mm(3).
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
One myeloma patient had graft failure in the AC Arm. 2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC Arm)
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 39 42
Median (Full Range)
Unit of Measure: Days to neutrophil engraftment
11
(3 to 19)
9
(7 to 36)
10.Secondary Outcome
Title Days to Engraftment of Platelets
Hide Description Platelet recovery: designated by the first of 7 days where the platelet count remains above 20,000/mm(3) without transfusion support
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC Arm)
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 39 42
Median (Full Range)
Unit of Measure: Days
19
(1 to 99)
14
(1 to 431)
11.Secondary Outcome
Title Days to Engraftment of Lymphocytes
Hide Description Lymphocyte recovery: designated by the first of 3 consecutive days with absolute lymphocyte count (ALC) above 500/mm(3).
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC Arm)
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 39 42
Median (Full Range)
Unit of Measure: Days
16
(1 to 194)
76
(16 to 264)
12.Secondary Outcome
Title Overall Survival
Hide Description Time between the first day of transplant to the day of death.
Time Frame Patients were followed for an average of up to 5 years.
Hide Outcome Measure Data
Hide Analysis Population Description
2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 39 42
Median (95% Confidence Interval)
Unit of Measure: Months
41.7 [1] 
(26.7 to NA)
18.8 [1] 
(10.4 to NA)
[1]
The upper limit is undefined because there are too few deaths for it to be determined.
13.Secondary Outcome
Title Early Treatment Related Mortality
Hide Description Any death occurring within 28 days after transplantation in a patient in continuous remission.
Time Frame Less than or equal to 28 days after transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (C) Arm
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 39 42
Measure Type: Number
Unit of Measure: participants
1 0
14.Secondary Outcome
Title Percentage of Participants With Late Treatment Related Mortality
Hide Description Any death occurring 28 days or more after transplantation in a patient in continuous remission.
Time Frame Greater than 28 days after transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 39 42
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28
(14 to 43)
29
(16 to 44)
15.Secondary Outcome
Title Decline in Homeostatic Cytokine Interleukin 7 (IL-7) Post-Transplant
Hide Description During depletion of lymphocytes during transplant conditioning, levels of homeostatic cytokines increase in the blood. These then decline with the expansion of new donor-derived cells. The rapidity of decline may predict acute graft versus host disease (AGVHD). Decline in cytokine IL-7 will be assessed by the enzyme-linked immunosorbent assay (ELISA).
Time Frame Day 0, 1 week and 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Following the focus on chronic graft-versus host disease (GVHD) as a primary outcome measure in 2011, this measure was not assessed.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (C) Arm
Hide Arm/Group Description:
Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
16.Secondary Outcome
Title Immune Reconstitution of Normal Killer (NK) Cells
Hide Description Cluster of differentiation 3 (CD3) - cluster of differentiation 56 (CD56) + Natural Killer (NK) cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.
Time Frame 2 weeks, and 1, 3, 6, 12, and 24 months post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included. A total of 5 completed participants did not contribute data due to missing samples, and participants who died and were not able to supply samples for the time points indicated.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:

TMS Arm Rituximab: 375 mg/m2 IV, day 1 for patients with cluster of differentiation 20 (CD20)-positive disease Allogenic stem cell transplant (ASCT):Allogenic stem cell transplant Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna:1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3 TMS: Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated Methotrexate: 5 mg/m2 IV over 15 minutes on days 1, 3, 6, and 11 Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.

FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy

Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 38 39
Median (Full Range)
Unit of Measure: Cells/µl
2 weeks Number Analyzed 36 participants 39 participants
123
(5 to 538)
15
(0 to 331)
1 month Number Analyzed 38 participants 37 participants
270
(41 to 940)
31
(0 to 936)
3 months Number Analyzed 34 participants 34 participants
134
(22 to 575)
124
(1 to 794)
6 months Number Analyzed 30 participants 28 participants
136
(25 to 442)
202
(1 to 831)
12 months Number Analyzed 25 participants 24 participants
134
(12 to 366)
150
(16 to 1043)
24 months Number Analyzed 22 participants 17 participants
133
(27 to 798)
307
(133 to 1336)
17.Secondary Outcome
Title Immune Reconstitution of Cluster of Differentiation 4 (CD4) T Cell Populations
Hide Description Cluster of Differentiation 3 (CD3)+CD4+ and CD3+Cluster of Differentiation 8 (CD8)+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.
Time Frame 2 weeks, and 1, 3, 6, 12 and 24 months post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included. A total of 5 completed participants did not contribute data due to missing samples, and participants who died and were not able to supply samples for the time points indicated.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:

TMS Arm Rituximab: 375 mg/m2 IV, day 1 for patients with cluster of differentiation 20 (CD20)-positive disease Allogenic stem cell transplant (ASCT):Allogenic stem cell transplant Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna:1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3 TMS: Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated Methotrexate: 5 mg/m2 IV over 15 minutes on days 1, 3, 6, and 11 Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.

FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy

Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 38 39
Median (Full Range)
Unit of Measure: Cells/µl
2 weeks Number Analyzed 36 participants 39 participants
171
(14 to 536)
0
(0 to 131)
1 month Number Analyzed 38 participants 37 participants
285
(15 to 2816)
21
(0 to 276)
3 months Number Analyzed 34 participants 34 participants
297
(3 to 1178)
61
(9 to 1109)
6 months Number Analyzed 30 participants 28 participants
387
(79 to 1126)
121
(26 to 2201)
12 months Number Analyzed 25 participants 24 participants
447
(55 to 1821)
132
(7 to 619)
24 months Number Analyzed 22 participants 17 participants
451
(143 to 893)
373
(64 to 1765)
18.Secondary Outcome
Title Immune Reconstitution of Cluster of Differentiation 8 (CD8) T Cell Populations
Hide Description Cluster of differentiation 3 (CD3)+cluster of differentiation 4 (CD4)+ and CD3+CD8+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.
Time Frame 2 weeks, 1, 3, 6, 12 and 24 months post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included. A total of 5 completed participants did not contribute data due to missing samples, and participants who died and were not able to supply samples for the time points indicated.
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description:

TMS Arm Rituximab: 375 mg/m2 IV, day 1 for patients with cluster of differentiation 20 (CD20)-positive disease Allogenic stem cell transplant (ASCT):Allogenic stem cell transplant Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna:1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3 TMS: Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated Methotrexate: 5 mg/m2 IV over 15 minutes on days 1, 3, 6, and 11 Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.

FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy

Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Overall Number of Participants Analyzed 38 39
Median (Full Range)
Unit of Measure: Cells/µl
2 weeks Number Analyzed 36 participants 39 participants
72
(9 to 560)
1
(0 to 240)
1 month Number Analyzed 38 participants 37 participants
204
(10 to 2147)
6
(0 to 430)
3 months Number Analyzed 34 participants 34 participants
334
(3 to 1054)
54
(1 to 846)
6 months Number Analyzed 30 participants 28 participants
429
(79 to 1487)
158
(0 to 1302)
12 months Number Analyzed 25 participants 24 participants
485
(64 to 1844)
243
(1 to 2861)
24 months Number Analyzed 22 participants 17 participants
434
(121 to 1928)
502
(92 to 4239)
Time Frame 103 months and 22 days
Adverse Event Reporting Description One participant was enrolled and given induction chemotherapy but was never randomized to Arm TMS or AC. Subject had one AE (infection with normal ANC or Grade 1 or 2 neutrophils: Pharynx). Subject was taken off study for disease progression and died.
 
Arm/Group Title A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Hide Arm/Group Description

TMS Arm

Rituximab: Rituximab: 375 mg/m2 IV, day 1 for patients with CD20-positive disease

Allogenic stem cell transplant (ASCT): Allogenic stem cell transplant

Conditioning Chemotherapy: Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3

TMS: Tacrolimus: 0.02 mg/kg , start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated Methotrexate: 5 mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.

FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy

AC Arm

Rituximab: Rituximab: 375 mg/m2 IV, day 1 for patients with CD20-positive disease

Cyclosporine: Cyclosporine: IV over 2 hours or orally every 12 hours on days -1 to 100, followed by a taper if GVHD does not develop.

Allogenic stem cell transplant (ASCT): Allogenic stem cell transplant

Conditioning Chemotherapy: Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3

FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy EPOCH-F: Fludarabine:25 mg/m2 per day IV infusion over 30 minutes, daily on days 1-4 Etoposide :50 mg/m2 per day continuous IV infusion over 24 hours on days 1-4 Doxorubicin:10 mg/m2/d

All-Cause Mortality
A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   8/44 (18.18%)      19/45 (42.22%)    
Show Serious Adverse Events Hide Serious Adverse Events
A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   36/44 (81.82%)      41/45 (91.11%)    
Blood and lymphatic system disorders     
Edema: limb  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Edema: viscera  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Hemoglobin  1  3/44 (6.82%)  10 2/45 (4.44%)  4
Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Iron overload  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Leukocytes (total WBC)  1  0/44 (0.00%)  0 2/45 (4.44%)  4
Lymphopenia  1  1/44 (2.27%)  1 2/45 (4.44%)  2
Neutrophils/granulocytes (ANC/AGC)  1  3/44 (6.82%)  4 1/45 (2.22%)  3
PTT (Partial Thromboplastin Time)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Platelets  1  1/44 (2.27%)  2 2/45 (4.44%)  11
Thrombotic microangiopathy  1 [1]  2/44 (4.55%)  2 1/45 (2.22%)  1
Cardiac disorders     
Cardiac ischemia/infarction  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Cardiopulmonary arrest, cause unknown (non-fatal)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Hypertension  1  0/44 (0.00%)  0 5/45 (11.11%)  5
Hypotension  1  3/44 (6.82%)  4 5/45 (11.11%)  6
Left ventricular diastolic dysfunction  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Left ventricular systolic dysfunction  1  2/44 (4.55%)  3 4/45 (8.89%)  4
Right ventricular dysfunction (cor pulmonale)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Supraventricular and nodal arrhythmia::Atrial fibrillation  1  3/44 (6.82%)  5 0/45 (0.00%)  0
Supraventricular and nodal arrhythmia::Sinus tachycardia  1  0/44 (0.00%)  0 2/45 (4.44%)  2
Supraventricular and nodal arrhythmia::Supraventricular tachycardia  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Ventricular arrhythmia::Ventricular tachycardia  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Endocrine disorders     
Adrenal insufficiency  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Pancreatic endocrine: glucose intolerance  1  2/44 (4.55%)  2 1/45 (2.22%)  1
Eye disorders     
Dry eye syndrome  1  3/44 (6.82%)  3 0/45 (0.00%)  0
Ocular/Visual - Other  1 [2]  0/44 (0.00%)  0 1/45 (2.22%)  1
Gastrointestinal disorders     
Colitis  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Colitis, infectious (e.g., Clostridium difficile)  1  5/44 (11.36%)  8 7/45 (15.56%)  12
Diarrhea  1  8/44 (18.18%)  9 8/45 (17.78%)  10
Dysphagia (difficulty swallowing)  1  1/44 (2.27%)  1 2/45 (4.44%)  2
Esophagitis  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Gastritis (including bile reflux gastritis)  1  2/44 (4.55%)  2 0/45 (0.00%)  0
Heartburn/dyspepsia  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Hemorrhage, GI::Abdomen NOS  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Hemorrhage, GI::Duodenum  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Hemorrhage, GI::Lower GI NOS  1  0/44 (0.00%)  0 3/45 (6.67%)  3
Hemorrhage, GI::Rectum  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Hemorrhage, GI::Upper GI NOS  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Mucositis/stomatitis (clinical exam)::Oral cavity  1  3/44 (6.82%)  3 0/45 (0.00%)  0
Mucositis/stomatitis (functional/symptomatic)::Oral cavity  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Nausea  1  1/44 (2.27%)  1 2/45 (4.44%)  2
Pain::Abdomen NOS  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Perforation, GI::Small bowel NOS  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Stricture/stenosis (including anastomotic), GI::Esophagus  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Ulcer, GI::Duodenum  1  1/44 (2.27%)  1 0/45 (0.00%)  0
General disorders     
Death not associated with CTCAE term::Death NOS  1  4/44 (9.09%)  4 7/45 (15.56%)  7
Death not associated with CTCAE term::Disease progression NOS  1  3/44 (6.82%)  3 10/45 (22.22%)  10
Death not associated with CTCAE term::Multi-organ failure  1  1/44 (2.27%)  1 2/45 (4.44%)  2
Fatigue (asthenia, lethargy, malaise)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)  1  2/44 (4.55%)  2 1/45 (2.22%)  1
Tumor lysis syndrome  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Weight gain  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Hepatobiliary disorders     
Cholecystitis  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Liver dysfunction/failure (clinical)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Immune system disorders     
Allergic reaction/hypersensitivity (including drug fever)  1  2/44 (4.55%)  2 0/45 (0.00%)  0
Cytokine release syndrome/acute infusion reaction  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infections and infestations     
Febrile neutropenia  1 [3]  6/44 (13.64%)  7 6/45 (13.33%)  9
Infection:: Abdomen NOS  1 [4]  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection ::Bladder (urinary)  1 [5]  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection ::Blood  1 [5]  3/44 (6.82%)  3 8/45 (17.78%)  10
Infection::Catheter-related  1 [5]  1/44 (2.27%)  1 4/45 (8.89%)  5
Infection ::Lip/perioral  1 [5]  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection ::Lung (pneumonia)  1 [5]  4/44 (9.09%)  6 3/45 (6.67%)  3
Infection::Meninges (meningitis)  1 [5]  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection ::Muscle (infection myositis)  1 [5]  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection::Nose  1 [5]  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection::Rectum  1 [5]  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection::Sinus  1 [5]  2/44 (4.55%)  2 2/45 (4.44%)  2
Infection ::Trachea  1 [5]  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection::Upper airway NOS  1 [5]  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection ::Urinary tract NOS  1 [5]  2/44 (4.55%)  2 1/45 (2.22%)  1
Infection - Other  1 [6]  1/44 (2.27%)  3 2/45 (4.44%)  3
Infection with normal ANC or Grade 1 or 2 neutrophils::Bladder (urinary)  1  1/44 (2.27%)  1 1/45 (2.22%)  2
Infection with normal ANC or Grade 1 or 2 neutrophils::Blood  1  9/44 (20.45%)  15 21/45 (46.67%)  40
Infection with normal ANC or Grade 1 or 2 neutrophils::Brain (encephalitis, infectious)  1  3/44 (6.82%)  3 0/45 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils::Bronchus  1  2/44 (4.55%)  3 1/45 (2.22%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Catheter-related  1  4/44 (9.09%)  4 12/45 (26.67%)  14
Infection with normal ANC or Grade 1 or 2 neutrophils::Colon  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Esophagus  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils::Heart (endocarditis)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils::Liver  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Lung (pneumonia)  1  10/44 (22.73%)  18 13/45 (28.89%)  30
Infection with normal ANC or Grade 1 or 2 neutrophils::Meninges (meningitis)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils::Paranasal  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils::Pharynx  1  2/44 (4.55%)  2 1/45 (2.22%)  2
Infection with normal ANC or Grade 1 or 2 neutrophils::Sinus  1  4/44 (9.09%)  4 6/45 (13.33%)  8
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis)  1  2/44 (4.55%)  3 4/45 (8.89%)  5
Infection with normal ANC or Grade 1 or 2 neutrophils::Stomach  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Upper airway NOS  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Urinary tract NOS  1  1/44 (2.27%)  1 3/45 (6.67%)  4
Infection with normal ANC or Grade 1 or 2 neutrophils::Wound  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Infection with unknown ANC::Blood  1  2/44 (4.55%)  2 2/45 (4.44%)  2
Infection with unknown ANC::Catheter-related  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection with unknown ANC::Colon  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection with unknown ANC::Lung (pneumonia)  1  2/44 (4.55%)  2 1/45 (2.22%)  1
Metabolism and nutrition disorders     
ALT, SGPT (serum glutamic pyruvic transaminase)  1  4/44 (9.09%)  5 1/45 (2.22%)  2
AST, SGOT(serum glutamic oxaloacetic transaminase)  1  4/44 (9.09%)  6 1/45 (2.22%)  2
Albumin, serum-low (hypoalbuminemia)  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Alkaline phosphatase  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Bilirubin (hyperbilirubinemia)  1  3/44 (6.82%)  3 2/45 (4.44%)  2
Creatinine  1  3/44 (6.82%)  5 2/45 (4.44%)  3
Magnesium, serum-low (hypomagnesemia)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Phosphate, serum-low (hypophosphatemia)  1  1/44 (2.27%)  2 1/45 (2.22%)  1
Potassium, serum-high (hyperkalemia)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Potassium, serum-low (hypokalemia)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Sodium, serum-low (hyponatremia)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Uric acid, serum-high (hyperuricemia)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Musculoskeletal and connective tissue disorders     
Arthritis (non-septic)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Muscle weakness, generalized or specific area (not due to neuropathy)::Right-sided  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Musculoskeletal/Soft Tissue - Other  1 [7]  0/44 (0.00%)  0 1/45 (2.22%)  1
Myositis (inflammation/damage of muscle)  1  0/44 (0.00%)  0 2/45 (4.44%)  2
Pain::Back  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Secondary Malignancy - possibly related to cancer treatment (AML);  1 [8]  0/44 (0.00%)  0 4/45 (8.89%)  5
Secondary Malignancy - possibly related to cancer treatment (metastat. test cancer in lung)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Nervous system disorders     
Ataxia (incoordination)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
CNS cerebrovascular ischemia  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Cognitive disturbance  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Confusion  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Encephalopathy  1  0/44 (0.00%)  0 3/45 (6.67%)  3
Hemorrhage, CNS  1  0/44 (0.00%)  0 2/45 (4.44%)  2
Leukoencephalopathy (radiographic findings)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Seizure  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Somnolence/depressed level of consciousness  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Renal and urinary disorders     
Cystitis  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Renal failure  1  10/44 (22.73%)  12 6/45 (13.33%)  10
Renal/Genitourinary - Other (AKI, required CVVH)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Respiratory, thoracic and mediastinal disorders     
Adult Respiratory Distress Syndrome (ARDS)  1  0/44 (0.00%)  0 5/45 (11.11%)  6
Carbon monoxide diffusion capacity (DL(co))  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Dyspnea (shortness of breath)  1  4/44 (9.09%)  5 3/45 (6.67%)  3
Hemorrhage, pulmonary/upper respiratory::Lung  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Hemorrhage, pulmonary/upper respiratory::Nose  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Hypoxia  1  7/44 (15.91%)  10 8/45 (17.78%)  13
Pericardial effusion (non-malignant)  1  2/44 (4.55%)  2 0/45 (0.00%)  0
Pleural effusion (non-malignant)  1  2/44 (4.55%)  2 2/45 (4.44%)  2
Pneumonitis/pulmonary infiltrates  1  2/44 (4.55%)  3 5/45 (11.11%)  5
Pulmonary/Upper Respiratory - Other (Specify, respiratory failure)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Pulmonary/Upper Respiratory - Other (pleural thickening)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Skin and subcutaneous tissue disorders     
Dermatology/Skin - Other (Deep sclerosis per MRI, GVHD possible)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Rash/desquamation  1  4/44 (9.09%)  5 7/45 (15.56%)  10
Rash: hand-foot skin reaction  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Vascular disorders     
Thrombosis/embolism (vascular access-related)  1  2/44 (4.55%)  2 0/45 (0.00%)  0
Thrombosis/thrombus/embolism  1  4/44 (9.09%)  5 1/45 (2.22%)  1
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
[1]
(e.g., thrombotic thrombocytopenic purpura [TTP] or hemolytic uremic syndrome [HUS])
[2]
(idiopathic progressive retinal vasculitis; poss inflammatory process; uk etiology; total blindness)
[3]
(fever of unknown origin without clinically or microbiologically documented infection)(ANC <1.0 x 10e9/L, fever >=38.5 degrees C)
[4]
(documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L)::
[5]
(documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L)
[6]
(S. Aureus positive blood; gram-neg-rod; line infection)
[7]
(sclerodermic & fascial changes; leg cramping/edema possible GVHD, prednisone started)
[8]
possibly related to cancer treatment (PTLD(liver biopsy + 10/3/08, stomach bx 10/6/08), EBV associated; to cancer treatment (EBV associated PTLD, neck LN bx (+)10/12/11;to cancer treatment (EBV assoc. PTLD;tonsil bx 10/12/11;obstructing nasopharynx).
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm B - Cyclosporine (AC) Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   43/44 (97.73%)      42/45 (93.33%)    
Blood and lymphatic system disorders     
Edema: head and neck  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Edema: limb  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Fibrinogen  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Hemoglobin  1  26/44 (59.09%)  108 26/45 (57.78%)  150
Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis)  1  1/44 (2.27%)  1 3/45 (6.67%)  4
Iron overload  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Leukocytes (total WBC)  1  27/44 (61.36%)  118 26/45 (57.78%)  189
Lymphopenia  1  27/44 (61.36%)  143 27/45 (60.00%)  181
Neutrophils/granulocytes (ANC/AGC)  1  26/44 (59.09%)  109 27/45 (60.00%)  123
PTT (Partial Thromboplastin Time)  1  5/44 (11.36%)  5 8/45 (17.78%)  15
Platelets  1  25/44 (56.82%)  81 23/45 (51.11%)  106
Thrombotic microangiopathy  1 [1]  0/44 (0.00%)  0 4/45 (8.89%)  4
Cardiac disorders     
Cardiac General - Other (cardimyopathy)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Cardiac General - Other (heart failure, fluid overload)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Cardiac ischemia/infarction  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Hypertension  1  3/44 (6.82%)  3 7/45 (15.56%)  7
Hypotension  1  2/44 (4.55%)  2 3/45 (6.67%)  4
Left ventricular systolic dysfunction  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Myocarditis  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Pericardial effusion (non-malignant)  1  2/44 (4.55%)  2 1/45 (2.22%)  1
Pericarditis  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Prolonged QTc interval  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Supraventricular and nodal arrhythmia::Atrial fibrillation  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Supraventricular and nodal arrhythmia::Sinus tachycardia  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Congenital, familial and genetic disorders     
Right ventricular dysfunction (cor pulmonale)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Endocrine disorders     
Adrenal insufficiency  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Pancreatic endocrine: glucose intolerance  1  3/44 (6.82%)  3 1/45 (2.22%)  1
Thyroid function, low (hypothyroidism)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Eye disorders     
Dry eye syndrome  1  8/44 (18.18%)  8 2/45 (4.44%)  2
Ophthalmoplegia/diplopia (double vision)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Gastrointestinal disorders     
Anorexia  1  2/44 (4.55%)  2 2/45 (4.44%)  4
Colitis  1  1/44 (2.27%)  1 3/45 (6.67%)  3
Colitis, infectious (e.g., Clostridium difficile)  1  1/44 (2.27%)  1 2/45 (4.44%)  2
Diarrhea  1  20/44 (45.45%)  25 22/45 (48.89%)  32
Dry mouth/salivary gland (xerostomia)  1  4/44 (9.09%)  4 1/45 (2.22%)  1
Dysphagia (difficulty swallowing)  1  3/44 (6.82%)  4 1/45 (2.22%)  2
Esophagitis  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Fistula, GI::Anus  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Gastritis (including bile reflux gastritis)  1  3/44 (6.82%)  3 0/45 (0.00%)  0
Gastrointestinal - Other (GVHD)  1  2/44 (4.55%)  2 0/45 (0.00%)  0
Gastrointestinal - Other  1 [2]  0/44 (0.00%)  0 1/45 (2.22%)  1
Heartburn/dyspepsia  1  3/44 (6.82%)  3 0/45 (0.00%)  0
Hemorrhage, GI::Abdomen NOS  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Hemorrhage, GI::Anus  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Hemorrhage, GI::Lower GI NOS  1  1/44 (2.27%)  3 0/45 (0.00%)  0
Mucositis/stomatitis (clinical exam)::Oral cavity  1  10/44 (22.73%)  10 0/45 (0.00%)  0
Mucositis/stomatitis (functional/symptomatic)::Oral cavity  1  8/44 (18.18%)  8 2/45 (4.44%)  2
Nausea  1  16/44 (36.36%)  17 6/45 (13.33%)  7
Pain::Anus  1  2/44 (4.55%)  2 0/45 (0.00%)  0
Pain::Throat/pharynx/larynx  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Perforation, GI::Small bowel NOS  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Taste alteration (dysgeusia)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Vomiting  1  2/44 (4.55%)  2 0/45 (0.00%)  0
General disorders     
Fatigue (asthenia, lethargy, malaise)  1  2/44 (4.55%)  2 5/45 (11.11%)  5
Insomnia  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Rigors/chills  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Syndromes - Other (septic shock)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Weight loss  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Hepatobiliary disorders     
Liver dysfunction/failure (clinical)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Immune system disorders     
Allergic reaction/hypersensitivity (including drug fever)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Infections and infestations     
Febrile neutropenia  1 [3]  4/44 (9.09%)  4 9/45 (20.00%)  9
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)  1  3/44 (6.82%)  3 9/45 (20.00%)  12
Infection  1 [4]  0/44 (0.00%)  0 1/45 (2.22%)  2
Infection ::Bladder (urinary)  1 [5]  6/44 (13.64%)  6 3/45 (6.67%)  3
Infection::Blood  1 [5]  9/44 (20.45%)  12 11/45 (24.44%)  14
Infection::Brain (encephalitis, infectious)  1 [5]  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection ::Brain + Spinal cord (encephalomyelitis)  1 [5]  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection::Bronchus  1 [5]  2/44 (4.55%)  2 1/45 (2.22%)  1
Infection ::Catheter-related  1 [5]  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection ::Colon  1 [5]  2/44 (4.55%)  2 3/45 (6.67%)  3
Infection ::Eye NOS  1 [5]  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection ::Lip/perioral  1 [5]  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection ::Lung (pneumonia)  1 [5]  6/44 (13.64%)  8 6/45 (13.33%)  6
Infection::Oral cavity-gums (gingivitis)  1 [5]  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection Sinus  1 [6]  2/44 (4.55%)  2 1/45 (2.22%)  1
Infection::Skin (cellulites)  1 [5]  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection::Soft tissue NOS  1 [7]  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection ::Upper aerodigestive NOS  1 [5]  1/44 (2.27%)  1 1/45 (2.22%)  1
Infection:: Upper airway NOS  1 [5]  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection::Urinary tract NOS  1 [5]  2/44 (4.55%)  2 0/45 (0.00%)  0
Infection ::Wound  1 [5]  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection - Other (CMV reactivation)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection - Other (Rhinovirus, Coronavirus HKU1)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection - Other (Varicella zoster; noravirus)  1  2/44 (4.55%)  2 0/45 (0.00%)  0
Infection - Other (acinetobacter)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection - Other (dissiminated HSV)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Bladder (urinary)  1  3/44 (6.82%)  3 4/45 (8.89%)  5
Infection with normal ANC or Grade 1 or 2 neutrophils::Blood  1  20/44 (45.45%)  44 25/45 (55.56%)  62
Infection with normal ANC or Grade 1 or 2 neutrophils::Bronchus  1  1/44 (2.27%)  1 3/45 (6.67%)  3
Infection with normal ANC or Grade 1 or 2 neutrophils::Catheter-related  1  0/44 (0.00%)  0 2/45 (4.44%)  2
Infection with normal ANC or Grade 1 or 2 neutrophils::Colon  1  2/44 (4.55%)  2 2/45 (4.44%)  3
Infection with normal ANC or Grade 1 or 2 neutrophils::Conjunctiva  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Eye NOS  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Lung (pneumonia)  1  7/44 (15.91%)  8 12/45 (26.67%)  18
Infection with normal ANC or Grade 1 or 2 neutrophils::Nose  1  2/44 (4.55%)  3 1/45 (2.22%)  2
Infection with normal ANC or Grade 1 or 2 neutrophils::Paranasal  1  0/44 (0.00%)  0 2/45 (4.44%)  2
Infection with normal ANC or Grade 1 or 2 neutrophils::Penis  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Pharynx  1  2/44 (4.55%)  2 3/45 (6.67%)  5
Infection with normal ANC or Grade 1 or 2 neutrophils::Sinus  1  4/44 (9.09%)  6 9/45 (20.00%)  10
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis)  1  2/44 (4.55%)  2 3/45 (6.67%)  3
Infection with normal ANC or Grade 1 or 2 neutrophils::Stomach  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils::Trachea  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Upper aerodigestive NOS  1  1/44 (2.27%)  1 2/45 (4.44%)  3
Infection with normal ANC or Grade 1 or 2 neutrophils::Upper airway NOS  1  9/44 (20.45%)  14 9/45 (20.00%)  10
Infection with normal ANC or Grade 1 or 2 neutrophils::Urinary tract NOS  1  4/44 (9.09%)  4 5/45 (11.11%)  6
Infection with normal ANC or Grade 1 or 2 neutrophils::Vagina  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Wound  1  0/44 (0.00%)  0 3/45 (6.67%)  4
Infection with unknown ANC::Blood  1  4/44 (9.09%)  4 2/45 (4.44%)  3
Infection with unknown ANC::Bronchus  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with unknown ANC::Catheter-related  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with unknown ANC::Lung (pneumonia)  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Infection with unknown ANC::Sinus  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection with unknown ANC::Skin (cellulites)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with unknown ANC::Upper aerodigestive NOS  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Infection with unknown ANC::Upper airway NOS  1  6/44 (13.64%)  7 2/45 (4.44%)  2
Infection with unknown ANC::Urinary tract NOS  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Infection with unknown ANC::Wound  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Opportunistic infection associated with >=Grade 2 Lymphopenia  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Metabolism and nutrition disorders     
ALT, SGPT (serum glutamic pyruvic transaminase)  1  28/44 (63.64%)  75 17/45 (37.78%)  45
AST, SGOT(serum glutamic oxaloacetic transaminase)  1  26/44 (59.09%)  73 23/45 (51.11%)  50
Acidosis (metabolic or respiratory)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Albumin, serum-low (hypoalbuminemia)  1  9/44 (20.45%)  15 12/45 (26.67%)  23
Alkaline phosphatase  1  7/44 (15.91%)  20 6/45 (13.33%)  9
Alkalosis (metabolic or respiratory)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Amylase  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Bicarbonate, serum-low  1  1/44 (2.27%)  1 2/45 (4.44%)  2
Bilirubin (hyperbilirubinemia)  1  12/44 (27.27%)  22 16/45 (35.56%)  38
CPK (creatine phosphokinase)  1  1/44 (2.27%)  4 1/45 (2.22%)  1
Calcium, serum-high (hypercalcemia)  1  0/44 (0.00%)  0 2/45 (4.44%)  2
Calcium, serum-low (hypocalcemia)  1  0/44 (0.00%)  0 2/45 (4.44%)  2
Creatinine  1  9/44 (20.45%)  11 10/45 (22.22%)  16
GGT (gamma-Glutamyl transpeptidase)  1  3/44 (6.82%)  4 3/45 (6.67%)  3
Glucose, serum-high (hyperglycemia)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Lipase  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Magnesium, serum-high (hypermagnesemia)  1  13/44 (29.55%)  22 16/45 (35.56%)  26
Magnesium, serum-low (hypomagnesemia)  1  3/44 (6.82%)  4 9/45 (20.00%)  15
Metabolic/Laboratory - Other (pancytopenia; steroid induced hyperglycemia)  1  2/44 (4.55%)  2 0/45 (0.00%)  0
Phosphate, serum-low (hypophosphatemia)  1  20/44 (45.45%)  69 22/45 (48.89%)  53
Potassium, serum-high (hyperkalemia)  1  3/44 (6.82%)  3 10/45 (22.22%)  15
Potassium, serum-low (hypokalemia)  1  10/44 (22.73%)  16 17/45 (37.78%)  36
Sodium, serum-high (hypernatremia)  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Sodium, serum-low (hyponatremia)  1  6/44 (13.64%)  9 9/45 (20.00%)  11
Triglyceride, serum-high (hypertriglyceridemia)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Uric acid, serum-high (hyperuricemia)  1  4/44 (9.09%)  5 7/45 (15.56%)  16
Musculoskeletal and connective tissue disorders     
Joint-function  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Muscle weakness, generalized or specific area (not due to neuropathy)::Extremity-lower  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Osteonecrosis (avascular necrosis)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Pain::Back  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Pain::Joint  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Pain::Muscle  1  2/44 (4.55%)  2 0/45 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Secondary Malignancy - possibly related to cancer treatment (mucoepidermoid carcinoma)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Secondary Malignancy - possibly related to cancer treatment (squamous cell carcinoma lip)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Nervous system disorders     
Confusion  1  0/44 (0.00%)  0 1/45 (2.22%)  2
Dizziness  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Encephalopathy  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Leukoencephalopathy (radiographic findings)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Memory impairment  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Mood alteration::Anxiety  1  2/44 (4.55%)  2 2/45 (4.44%)  2
Mood alteration::Depression  1  1/44 (2.27%)  1 3/45 (6.67%)  3
Neurology - Other (delirium)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Neuropathy: motor  1  2/44 (4.55%)  2 2/45 (4.44%)  2
Neuropathy: sensory  1  4/44 (9.09%)  4 1/45 (2.22%)  1
Pain::Head/headache  1  2/44 (4.55%)  2 2/45 (4.44%)  2
Psychosis (hallucinations/delusions)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Seizure  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Syncope (fainting)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Renal and urinary disorders     
Cystitis  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Hemorrhage, GU::Bladder  1  3/44 (6.82%)  3 0/45 (0.00%)  0
Hemorrhage, GU::Urinary NOS  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Obstruction, GU::Bladder  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Pain::Urethra  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Renal failure  1  4/44 (9.09%)  5 4/45 (8.89%)  4
Renal/Genitourinary - Other (acute renal injury)  1 [8]  3/44 (6.82%)  4 0/45 (0.00%)  0
Renal/Genitourinary - Other (dysuria)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Renal/Genitourinary - Other (dysuria; hematuria; stent replacement)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Renal/Genitourinary - Other (failure; hematuria; insufficiency; dysuria)  1  0/44 (0.00%)  0 6/45 (13.33%)  7
Renal/Genitourinary - Other (fluid overload refractory to normal doses of Lasix)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Renal/Genitourinary - Other (hematuria)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Renal/Genitourinary - Other (insufficiency)  1  4/44 (9.09%)  4 0/45 (0.00%)  0
Urinary frequency/urgency  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Urinary retention (including neurogenic bladder)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Reproductive system and breast disorders     
Vaginal dryness  1  2/44 (4.55%)  2 2/45 (4.44%)  2
Vaginal mucositis  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Adult Respiratory Distress Syndrome (ARDS)  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Bronchospasm, wheezing  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Carbon monoxide diffusion capacity (DL(co))  1  3/44 (6.82%)  3 5/45 (11.11%)  5
Cough  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Dyspnea (shortness of breath)  1  4/44 (9.09%)  5 3/45 (6.67%)  3
FEV(1)  1  2/44 (4.55%)  3 1/45 (2.22%)  1
Hiccoughs (hiccups, singultus)  1  0/44 (0.00%)  0 2/45 (4.44%)  2
Hypoxia  1  5/44 (11.36%)  5 4/45 (8.89%)  8
Pleural effusion (non-malignant)  1  3/44 (6.82%)  3 2/45 (4.44%)  2
Pneumonitis/pulmonary infiltrates  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Pneumothorax  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Pulmonary/Upper Respiratory - Other (infiltrates)  1 [9]  0/44 (0.00%)  0 1/45 (2.22%)  2
Pulmonary/Upper Respiratory - Other (infiltrates; fungal pneumonia)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Skin breakdown/decubitus ulcer  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Wound complication, non-infectious  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Skin and subcutaneous tissue disorders     
Dermatology/Skin - Other (GVHD; cGVHD)  1  2/44 (4.55%)  2 0/45 (0.00%)  0
Dermatology/Skin - Other (MRSA abscess)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Dry skin  1  1/44 (2.27%)  1 1/45 (2.22%)  1
Hyperpigmentation  1  4/44 (9.09%)  5 0/45 (0.00%)  0
Induration/fibrosis (skin and subcutaneous tissue)  1  4/44 (9.09%)  5 0/45 (0.00%)  0
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Pruritus/itching  1  0/44 (0.00%)  0 2/45 (4.44%)  2
Rash/desquamation  1  19/44 (43.18%)  30 26/45 (57.78%)  39
Rash: acne/acneiform  1  3/44 (6.82%)  3 1/45 (2.22%)  1
Rash: hand-foot skin reaction  1  0/44 (0.00%)  0 1/45 (2.22%)  1
Ulceration  1  2/44 (4.55%)  2 2/45 (4.44%)  2
Vascular disorders     
Phlebitis (including superficial thrombosis)  1  1/44 (2.27%)  1 0/45 (0.00%)  0
Thrombosis/embolism (vascular access-related)  1  1/44 (2.27%)  1 2/45 (4.44%)  2
Thrombosis/thrombus/embolism  1  6/44 (13.64%)  6 2/45 (4.44%)  2
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
[1]
(e.g., thrombotic thrombocytopenic purpura [TTP] or hemolytic uremic syndrome [HUS])
[2]
(duodenal bx 1/24/11; very rare apoptotic cells CMV stains (-); steroids started for GVHD)
[3]
(fever of unknown origin without clinically or microbiologically documented infection)(ANC <1.0 x 10e9/L, fever >=38.5 degrees C)
[4]
(documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L)::Abdomen NOS
[5]
(documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L)
[6]
(documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L)::
[7]
(documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L
[8]
dysuria; hematuria; stent replacement; fluid overload refractory to normal doses of Lasix
[9]
Infiltrates; fungal pneumonia
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Steven Z. Pavletic
Organization: National Cancer Institute
Phone: 301- 402-4899
EMail: sp326h@nih.gov
Publications:
Layout table for additonal information
Responsible Party: Steven Pavletic, M.D., National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00520130     History of Changes
Other Study ID Numbers: 070195
07-C-0195
First Submitted: August 21, 2007
First Posted: August 23, 2007
Results First Submitted: November 17, 2016
Results First Posted: August 24, 2017
Last Update Posted: March 5, 2019