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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00520130
First Posted: August 23, 2007
Last Update Posted: August 24, 2017
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.
Information provided by (Responsible Party):
Steven Pavletic, M.D., National Institutes of Health Clinical Center (CC)
Results First Submitted: November 17, 2016  
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

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm 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.
B - Cyclosporine (AC) Arm 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.

Participant Flow:   Overall Study
    A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm   B - Cyclosporine (AC) Arm
STARTED   44   45 
COMPLETED   39   44 
NOT COMPLETED   5   1 
Disease progression on study                4                0 
Physician Decision                1                1 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Tacrolimus, Methotrexate, Sirolimus (TMS) Arm 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
Cyclosporine (AC) Arm 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 Total of all reporting groups

Baseline Measures
   Tacrolimus, Methotrexate, Sirolimus (TMS) Arm   Cyclosporine (AC) Arm   Total 
Overall Participants Analyzed 
[Units: Participants]
 44   45   89 
Age 
[Units: Participants]
Count of 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 
[Units: Years]
Mean (Standard Deviation)
 47.92  (14.68)   47.89  (13.4)   47.90  (14.04) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      16  36.4%      15  33.3%      31  34.8% 
Male      28  63.6%      30  66.7%      58  65.2% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of 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) 
[Units: Participants]
Count of 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 
[Units: Participants]
Count of Participants
     
United States   44   45   89 
Histology [1] 
[Units: Participants]
Count of 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] Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS); Cutaneous T Cell Lymphoma (CTCL)/Peripheral T Cell Lymphoma (PTCL)


  Outcome Measures
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1.  Primary:   Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD)   [ Time Frame: 6 months ]

2.  Primary:   Percentage of Participants With Chronic Graft Versus Host Disease (cGVHD)   [ Time Frame: 2 years post transplant ]

3.  Primary:   Recovery of Naïve Cluster of Differentiation 4 (CD4) T Cells   [ Time Frame: Recipient recovery at 6, 12 and 24 months post transplant ]

4.  Primary:   Recovery of Naïve Cluster of Differentiation 8 (CD8) T Cells   [ Time Frame: Recipient recovery at 6, 12 and 24 months post transplant ]

5.  Primary:   Changes in Cluster of Differentiation 4 (CD4) T Cell Receptor Vbeta Repertoire   [ Time Frame: Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant ]

6.  Primary:   Changes in CD8 T Cell Receptor Vbeta Repertoire   [ Time Frame: Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant ]

7.  Secondary:   Percentage of Participants With Grade III-IV Acute Graft Versus Host Disease (GVHD)   [ Time Frame: 6 months ]

8.  Secondary:   Toxicities   [ Time Frame: 103 months and 22 days ]

9.  Secondary:   Days to Engraftment of Neutrophils   [ Time Frame: 2 years ]

10.  Secondary:   Days to Engraftment of Platelets   [ Time Frame: 2 years ]

11.  Secondary:   Days to Engraftment of Lymphocytes   [ Time Frame: 2 years ]

12.  Secondary:   Overall Survival   [ Time Frame: Patients were followed for an average of up to 5 years. ]

13.  Secondary:   Early Treatment Related Mortality   [ Time Frame: Less than or equal to 28 days after transplantation ]

14.  Secondary:   Percentage of Participants With Late Treatment Related Mortality   [ Time Frame: Greater than 28 days after transplantation ]

15.  Secondary:   Decline in Homeostatic Cytokine Interleukin 7 (IL-7) Post-Transplant   [ Time Frame: Day 0, 1 week and 2 weeks ]

16.  Secondary:   Immune Reconstitution of Normal Killer (NK) Cells   [ Time Frame: 2 weeks, and 1, 3, 6, 12, and 24 months post transplant ]

17.  Secondary:   Immune Reconstitution of Cluster of Differentiation 4 (CD4) T Cell Populations   [ Time Frame: 2 weeks, and 1, 3, 6, 12 and 24 months post transplant ]

18.  Secondary:   Immune Reconstitution of Cluster of Differentiation 8 (CD8) T Cell Populations   [ Time Frame: 2 weeks, 1, 3, 6, 12 and 24 months post transplant ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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:  
Name/Title: Dr. Steven Z. Pavletic
Organization: National Cancer Institute
phone: 301- 402-4899
e-mail: sp326h@nih.gov


Publications:


Responsible Party: Steven Pavletic, M.D., National Institutes of Health Clinical Center (CC)
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: August 24, 2017