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Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant

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ClinicalTrials.gov Identifier: NCT01231412
Recruitment Status : Completed
First Posted : November 1, 2010
Results First Posted : December 4, 2017
Last Update Posted : March 13, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Brenda Sandmaier, Fred Hutchinson Cancer Research Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Aggressive Non-Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Diffuse Large B-Cell Lymphoma
Hematopoietic and Lymphoid Cell Neoplasm
Indolent Non-Hodgkin Lymphoma
Mantle Cell Lymphoma
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Prolymphocytic Leukemia
Recurrent Chronic Lymphocytic Leukemia
Recurrent Plasma Cell Myeloma
Refractory Chronic Lymphocytic Leukemia
Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Refractory Hodgkin Lymphoma
Small Lymphocytic Lymphoma
T-Cell Chronic Lymphocytic Leukemia
Waldenstrom Macroglobulinemia
Interventions Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Drug: Cyclosporine
Drug: Fludarabine Phosphate
Drug: Mycophenolate Mofetil
Procedure: Peripheral Blood Stem Cell Transplantation
Drug: Sirolimus
Radiation: Total-Body Irradiation
Enrollment 174
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus)
Hide Arm/Group Description

Patients receive FLU IV over 30 minutes on days -4 to -2. Patients also receive CSP PO BID on days -3 to 96 with taper to day 150 and MMF PO TID daily on days 0-29 and then BID on days 30-150 with taper to day 180. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Total-Body Irradiation: Undergo TBI

Patients receive FLU and CSP as in Arm I and sirolimus PO QD on days -3 to 150 with taper to day 180. Patients also receive MMF PO TID on days 0-29 and then BID on days 30-40. MMF will then be discontinued without taper unless GVHD or disease relapse/progression occurs. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Sirolimus: Given PO

Total-Body Irradiation: Undergo TBI

Patients receive CSP orally (PO) twice daily (BID) on days -3 to 96 with taper to day 150 and and sirolimus PO once daily (QD) on days -3 to 150 with taper to day 180. Arm removed as of 14-Sep-2011
Period Title: Overall Study
Started 77 91 6
Completed 77 90 6
Not Completed 0 1 0
Arm/Group Title Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus) Total
Hide Arm/Group Description

Patients receive FLU IV over 30 minutes on days -4 to -2. Patients also receive CSP PO BID on days -3 to 96 with taper to day 150 and MMF PO TID daily on days 0-29 and then BID on days 30-150 with taper to day 180. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Total-Body Irradiation: Undergo TBI

Patients receive FLU and CSP as in Arm I and sirolimus PO QD on days -3 to 150 with taper to day 180. Patients also receive MMF PO TID on days 0-29 and then BID on days 30-40. MMF will then be discontinued without taper unless GVHD or disease relapse/progression occurs. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Sirolimus: Given PO

Total-Body Irradiation: Undergo TBI

Patients receive CSP orally (PO) twice daily (BID) on days -3 to 96 with taper to day 150 and and sirolimus PO once daily (QD) on days -3 to 150 with taper to day 180. Arm removed as of 14-Sep-2011 Total of all reporting groups
Overall Number of Baseline Participants 77 91 6 174
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 91 participants 6 participants 174 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
52
  67.5%
50
  54.9%
4
  66.7%
106
  60.9%
>=65 years
25
  32.5%
41
  45.1%
2
  33.3%
68
  39.1%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 77 participants 91 participants 6 participants 174 participants
61.94
(18.2 to 77.09)
63.75
(41.02 to 79)
59.515
(36.47 to 67.83)
62.655
(18.2 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 91 participants 6 participants 174 participants
Female
27
  35.1%
28
  30.8%
2
  33.3%
57
  32.8%
Male
50
  64.9%
63
  69.2%
4
  66.7%
117
  67.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 77 participants 91 participants 6 participants 174 participants
United States 65 78 6 149
Denmark 10 12 0 22
Germany 2 1 0 3
1.Primary Outcome
Title Incidences of Acute Grade II-IV GVHD, Exclusive of GVHD That Occurs as a Result of Alterations to Immunosuppressive Therapy in Response to Relapse or Progression
Hide Description

Number of patients who developed acute GVHD post-transplant. aGVHD Stages

Skin:

a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation

Liver:

bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL

Gut:

Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall.

aGVHD Grades Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

Time Frame At day 100 post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject on Arm II aborted transplant during conditioning and subsequently went on to transplant on a different study. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus)
Hide Arm/Group Description:

Patients receive FLU IV over 30 minutes on days -4 to -2. Patients also receive CSP PO BID on days -3 to 96 with taper to day 150 and MMF PO TID daily on days 0-29 and then BID on days 30-150 with taper to day 180. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Total-Body Irradiation: Undergo TBI

Patients receive FLU and CSP as in Arm I and sirolimus PO QD on days -3 to 150 with taper to day 180. Patients also receive MMF PO TID on days 0-29 and then BID on days 30-40. MMF will then be discontinued without taper unless GVHD or disease relapse/progression occurs. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Sirolimus: Given PO

Total-Body Irradiation: Undergo TBI

Patients receive CSP orally (PO) twice daily (BID) on days -3 to 96 with taper to day 150 and and sirolimus PO once daily (QD) on days -3 to 150 with taper to day 180. Arm removed as of 14-Sep-2011
Overall Number of Participants Analyzed 77 90 6
Measure Type: Count of Participants
Unit of Measure: Participants
39
  50.6%
22
  24.4%
3
  50.0%
2.Secondary Outcome
Title Incidences of Chronic Extensive GVHD
Hide Description Number of patients who developed chronic extensive GVHD post-transplant. The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.
Time Frame Up to 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject on Arm II aborted transplant during conditioning and subsequently went on to transplant on a different study. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus)
Hide Arm/Group Description:

Patients receive FLU IV over 30 minutes on days -4 to -2. Patients also receive CSP PO BID on days -3 to 96 with taper to day 150 and MMF PO TID daily on days 0-29 and then BID on days 30-150 with taper to day 180. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Total-Body Irradiation: Undergo TBI

Patients receive FLU and CSP as in Arm I and sirolimus PO QD on days -3 to 150 with taper to day 180. Patients also receive MMF PO TID on days 0-29 and then BID on days 30-40. MMF will then be discontinued without taper unless GVHD or disease relapse/progression occurs. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Sirolimus: Given PO

Total-Body Irradiation: Undergo TBI

Patients receive CSP orally (PO) twice daily (BID) on days -3 to 96 with taper to day 150 and and sirolimus PO once daily (QD) on days -3 to 150 with taper to day 180. Arm removed as of 14-Sep-2011
Overall Number of Participants Analyzed 77 90 6
Measure Type: Count of Participants
Unit of Measure: Participants
38
  49.4%
43
  47.8%
3
  50.0%
3.Secondary Outcome
Title Incidences of Grade III-IV Acute GVHD
Hide Description

Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages

Skin:

a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation

Liver:

bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL

Gut:

Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall.

aGVHD Grades Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

Time Frame Up to 100 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject on Arm II aborted transplant during conditioning and subsequently went on to transplant on a different study. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus)
Hide Arm/Group Description:

Patients receive FLU IV over 30 minutes on days -4 to -2. Patients also receive CSP PO BID on days -3 to 96 with taper to day 150 and MMF PO TID daily on days 0-29 and then BID on days 30-150 with taper to day 180. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Total-Body Irradiation: Undergo TBI

Patients receive FLU and CSP as in Arm I and sirolimus PO QD on days -3 to 150 with taper to day 180. Patients also receive MMF PO TID on days 0-29 and then BID on days 30-40. MMF will then be discontinued without taper unless GVHD or disease relapse/progression occurs. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Sirolimus: Given PO

Total-Body Irradiation: Undergo TBI

Patients receive CSP orally (PO) twice daily (BID) on days -3 to 96 with taper to day 150 and and sirolimus PO once daily (QD) on days -3 to 150 with taper to day 180. Arm removed as of 14-Sep-2011
Overall Number of Participants Analyzed 77 90 6
Measure Type: Count of Participants
Unit of Measure: Participants
8
  10.4%
2
   2.2%
0
   0.0%
4.Secondary Outcome
Title Incidences of Non-relapse Mortality
Hide Description Number of subjects expired without disease progression/relapse.
Time Frame Up to 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject on Arm II aborted transplant during conditioning and subsequently went on to transplant on a different study. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus)
Hide Arm/Group Description:

Patients receive FLU IV over 30 minutes on days -4 to -2. Patients also receive CSP PO BID on days -3 to 96 with taper to day 150 and MMF PO TID daily on days 0-29 and then BID on days 30-150 with taper to day 180. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Total-Body Irradiation: Undergo TBI

Patients receive FLU and CSP as in Arm I and sirolimus PO QD on days -3 to 150 with taper to day 180. Patients also receive MMF PO TID on days 0-29 and then BID on days 30-40. MMF will then be discontinued without taper unless GVHD or disease relapse/progression occurs. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Sirolimus: Given PO

Total-Body Irradiation: Undergo TBI

Patients receive CSP orally (PO) twice daily (BID) on days -3 to 96 with taper to day 150 and and sirolimus PO once daily (QD) on days -3 to 150 with taper to day 180. Arm removed as of 14-Sep-2011
Overall Number of Participants Analyzed 77 90 6
Measure Type: Count of Participants
Unit of Measure: Participants
12
  15.6%
4
   4.4%
0
   0.0%
5.Secondary Outcome
Title Overall Survival
Hide Description Number of subjects surviving post-transplant.
Time Frame Up to 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject on Arm II aborted transplant during conditioning and subsequently went on to transplant on a different study. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus)
Hide Arm/Group Description:

Patients receive FLU IV over 30 minutes on days -4 to -2. Patients also receive CSP PO BID on days -3 to 96 with taper to day 150 and MMF PO TID daily on days 0-29 and then BID on days 30-150 with taper to day 180. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Total-Body Irradiation: Undergo TBI

Patients receive FLU and CSP as in Arm I and sirolimus PO QD on days -3 to 150 with taper to day 180. Patients also receive MMF PO TID on days 0-29 and then BID on days 30-40. MMF will then be discontinued without taper unless GVHD or disease relapse/progression occurs. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Sirolimus: Given PO

Total-Body Irradiation: Undergo TBI

Patients receive CSP orally (PO) twice daily (BID) on days -3 to 96 with taper to day 150 and and sirolimus PO once daily (QD) on days -3 to 150 with taper to day 180. Arm removed as of 14-Sep-2011
Overall Number of Participants Analyzed 77 90 6
Measure Type: Count of Participants
Unit of Measure: Participants
53
  68.8%
75
  83.3%
6
 100.0%
6.Secondary Outcome
Title Number of Participants With Relapse/Progression
Hide Description

Relapse/Progression criteria:

CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever >38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes >20%.

AML, ALL, MDS >5% blasts by morphologic or flow cytometric evaluation of the BMA or appearance of extramedullary disease CLL ≥1 of: Physical exam/imaging studies ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation.

NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions.

MM

≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or numb

Time Frame Up to 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject on Arm II aborted transplant during conditioning and subsequently went on to transplant on a different study. This subject was counted towards accrual but not evaluated with respect to outcome measures.
Arm/Group Title Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus)
Hide Arm/Group Description:

Patients receive FLU IV over 30 minutes on days -4 to -2. Patients also receive CSP PO BID on days -3 to 96 with taper to day 150 and MMF PO TID daily on days 0-29 and then BID on days 30-150 with taper to day 180. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Total-Body Irradiation: Undergo TBI

Patients receive FLU and CSP as in Arm I and sirolimus PO QD on days -3 to 150 with taper to day 180. Patients also receive MMF PO TID on days 0-29 and then BID on days 30-40. MMF will then be discontinued without taper unless GVHD or disease relapse/progression occurs. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Sirolimus: Given PO

Total-Body Irradiation: Undergo TBI

Patients receive CSP orally (PO) twice daily (BID) on days -3 to 96 with taper to day 150 and and sirolimus PO once daily (QD) on days -3 to 150 with taper to day 180. Arm removed as of 14-Sep-2011
Overall Number of Participants Analyzed 77 90 6
Measure Type: Count of Participants
Unit of Measure: Participants
16
  20.8%
16
  17.8%
1
  16.7%
Time Frame AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus)
Hide Arm/Group Description

Patients receive FLU IV over 30 minutes on days -4 to -2. Patients also receive CSP PO BID on days -3 to 96 with taper to day 150 and MMF PO TID daily on days 0-29 and then BID on days 30-150 with taper to day 180. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Total-Body Irradiation: Undergo TBI

Patients receive FLU and CSP as in Arm I and sirolimus PO QD on days -3 to 150 with taper to day 180. Patients also receive MMF PO TID on days 0-29 and then BID on days 30-40. MMF will then be discontinued without taper unless GVHD or disease relapse/progression occurs. Patients undergo allogeneic PBSCT on day 0 following the TBI.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT

Cyclosporine: Given PO or IV

Fludarabine Phosphate: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSCT

Sirolimus: Given PO

Total-Body Irradiation: Undergo TBI

Patients receive CSP orally (PO) twice daily (BID) on days -3 to 96 with taper to day 150 and and sirolimus PO once daily (QD) on days -3 to 150 with taper to day 180. Arm removed as of 14-Sep-2011
All-Cause Mortality
Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/77 (0.00%)      0/90 (0.00%)      0/6 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm I (MMF and CSP) Arm II (MMF, CSP, and Sirolimus) Arm 0 (CSP and Sirolimus)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/77 (35.06%)      26/90 (28.89%)      3/6 (50.00%)    
Blood and lymphatic system disorders       
Febrile neutropenia   6/77 (7.79%)  7 3/90 (3.33%)  3 0/6 (0.00%)  0
Hemolysis   3/77 (3.90%)  3 0/90 (0.00%)  0 0/6 (0.00%)  0
Cardiac disorders       
Atrial fibrillation   1/77 (1.30%)  1 1/90 (1.11%)  1 0/6 (0.00%)  0
Ventricular arrhythmia   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Colonic hemorrhage   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Diarrhea   2/77 (2.60%)  2 1/90 (1.11%)  1 0/6 (0.00%)  0
Fecal incontinence   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Gastric ulcer   0/77 (0.00%)  0 1/90 (1.11%)  1 0/6 (0.00%)  0
Gastritis   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Mucositis oral   1/77 (1.30%)  1 2/90 (2.22%)  2 0/6 (0.00%)  0
General disorders       
Fever   0/77 (0.00%)  0 1/90 (1.11%)  1 0/6 (0.00%)  0
Immune system disorders       
Allergic reaction   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Infections and infestations       
Encephalitis infection   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Enterocolitis infectious   0/77 (0.00%)  0 1/90 (1.11%)  1 0/6 (0.00%)  0
Pleural infection   0/77 (0.00%)  0 1/90 (1.11%)  1 0/6 (0.00%)  0
Sepsis   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Skin infection   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Investigations       
Alanine aminotransferase increased   2/77 (2.60%)  2 0/90 (0.00%)  0 0/6 (0.00%)  0
Aspartate aminotransferase increased   1/77 (1.30%)  1 1/90 (1.11%)  1 0/6 (0.00%)  0
Blood bilirubin increased   7/77 (9.09%)  7 1/90 (1.11%)  1 1/6 (16.67%)  1
Creatinine increased   4/77 (5.19%)  4 4/90 (4.44%)  4 0/6 (0.00%)  0
Weight loss   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Metabolism and nutrition disorders       
Hypertriglyceridemia   0/77 (0.00%)  0 4/90 (4.44%)  4 0/6 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Treatment related secondary malignancy   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Nervous system disorders       
Syncope   1/77 (1.30%)  1 1/90 (1.11%)  1 1/6 (16.67%)  1
Renal and urinary disorders       
Acute kidney injury   0/77 (0.00%)  0 3/90 (3.33%)  3 0/6 (0.00%)  0
Chronic kidney disease   0/77 (0.00%)  0 1/90 (1.11%)  1 0/6 (0.00%)  0
Renal and urinary disorders - Other (Hemorrhagic cystitis)   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Urinary retention   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
"Adult respiratory distress syndrome"   3/77 (3.90%)  3 0/90 (0.00%)  0 1/6 (16.67%)  1
Bronchopulmonary hemorrhage   1/77 (1.30%)  1 2/90 (2.22%)  2 0/6 (0.00%)  0
Hypoxia   6/77 (7.79%)  6 3/90 (3.33%)  4 0/6 (0.00%)  0
Laryngeal inflammation   0/77 (0.00%)  0 0/90 (0.00%)  0 1/6 (16.67%)  1
Lung infection   3/77 (3.90%)  3 0/90 (0.00%)  0 0/6 (0.00%)  0
Pleural effusion   0/77 (0.00%)  0 1/90 (1.11%)  1 0/6 (0.00%)  0
Pulmonary edema   1/77 (1.30%)  1 0/90 (0.00%)  0 0/6 (0.00%)  0
Respiratory failure   2/77 (2.60%)  2 1/90 (1.11%)  1 0/6 (0.00%)  0
Vascular disorders       
Hypotension   2/77 (2.60%)  3 0/90 (0.00%)  0 0/6 (0.00%)  0
Thromboembolic event   2/77 (2.60%)  3 1/90 (1.11%)  2 0/6 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Brenda M. Sandmaier
Organization: Fred Hutchinson Cancer Research Center
Phone: (206) 667-4961
Responsible Party: Brenda Sandmaier, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01231412     History of Changes
Other Study ID Numbers: 2448.00
NCI-2010-02035 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2448.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P01CA018029 ( U.S. NIH Grant/Contract )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: October 28, 2010
First Posted: November 1, 2010
Results First Submitted: November 1, 2017
Results First Posted: December 4, 2017
Last Update Posted: March 13, 2018