Double Cord Versus Haploidentical (BMT CTN 1101)
|Acute Lymphocytic Leukemia Acute Myelogenous Leukemia Burkitt's Lymphoma Follicular Lymphoma Hodgkin Lymphoma Mantle Cell Lymphoma Non-Hodgkin Lymphoma||Biological: Haploidentical Bone Marrow Transplant Biological: Double Umbilical Cord Blood Transplant||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Multi-Center, Phase III, Randomized Trial of Reduced Intensity Conditioning (RIC) and Transplantation of Double Unrelated Umbilical Cord Blood (dUCB) Versus HLA-Haploidentical Related Bone Marrow (Haplo) for Patients With Hematologic Malignancies (BMT CTN #1101)|
- Progression Free Survival (PFS) [ Time Frame: Year 2 ]The primary endpoint is PFS at 2-years from the date of randomization. PFS is defined as the time interval from date of randomization and time to relapse/progression, to death or to last follow-up.
- Neutrophil Recovery [ Time Frame: Day 56 ]Neutrophil recovery is defined as achieving an absolute neutrophil count greater than or equal to 500/mm^3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil recovery.
- Primary Graft Failure [ Time Frame: Day 56 ]Primary graft failure is defined as less than 5% donor chimerism on all measurements up to and including Day 56.
- Secondary Graft Failure [ Time Frame: Day 100 ]Secondary graft failure is defined as initial neutrophil recovery followed by neutropenia with less than 5% donor chimerism in the absence of recurrent disease. If chimerism assays were not performed and absolute neutrophil count less than 500/mm^3 is sustained , then it will be counted as a secondary graft failure.
- Platelet Recovery [ Time Frame: Days 100 and 180 ]Platelet recovery is defined by two different metrics as the first day of a sustained platelet count greater than 20,000/mm^3 or greater than 50,000/mm^3 with no platelet transfusions in the preceding seven days. The first day of the sustained platelet count will be designated the day of platelet engraftment.
- Donor Cell Engraftment [ Time Frame: Day 56 ]Donor cell engraftment is defined as donor chimerism greater than or equal to 5% on greater than or equal to Day 56 after transplantation. Chimerism may be evaluated in whole blood or blood cell fractions, including CD3 and CD33 or CD15 fractions).
- Acute Graft-versus-Host Disease (aGVHD) [ Time Frame: Year 3 ]The cumulative incidences of grade II - IV and III - IV acute aGVHD will be determined. The time to onset of acute grades II-IV aGVHD and grades III-IV aGVHD will be recorded, as well as the maximum grade achieved.
- Chronic Graft-versus-Host Disease (cGHVD) [ Time Frame: Year 3 ]The cumulative incidence of cGVHD will be determined. Data will be collected directly from providers and chart review according to the recommendations of the NIH Consensus Conference. The NIH global severity scores of mild, moderate and severe chronic GVHD will be assessed.
- Overall Survival [ Time Frame: Year 3 ]Overall survival is defined as the time interval between date of randomization and death from any cause or for surviving patients, to last follow-up.
- Treatment-related Mortality (TRM) [ Time Frame: Year 1 and 2 ]The cumulative incidence of TRM will be estimated, event for this endpoint is death without evidence of disease progression or recurrence.
- Infections [ Time Frame: Year 3 ]All Grade 2 and 3 infections will be reported.
|Actual Study Start Date:||June 2012|
|Estimated Study Completion Date:||June 2019|
|Estimated Primary Completion Date:||June 2018 (Final data collection date for primary outcome measure)|
Experimental: Haploidentical Bone Marrow Transplant
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Biological: Haploidentical Bone Marrow Transplant
The conditioning regimen consists of:
Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2 Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5 Total body irradiation (TBI) 200cGy Day -1
The GVHD prophylaxis regimen consists of:
Cy 50 mg/kg IV Days 3, 4 Tacrolimus (IV or PO) beginning Day 5 Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Experimental: Double Umbilical Cord Blood Transplant
Participants will receive a double umbilical cord blood transplant using a reduced intensity conditioning regimen.
Biological: Double Umbilical Cord Blood Transplant
The preparative regimen consists of:
Fludarabine 40 mg/m2 IV Days -6, -5, -4,-3, -2 Cyclophosphamide 50 mg/kg IV Day -6 Total Body Irradiation (TBI) 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the 3 months of enrollment or an autologous transplant within 24 months of enrollment or 300 cGy Day -1 for patients who have not received cytotoxic chemotherapy within the 3 months of enrollment and who have not received an autologous transplant within 24 months of enrollment.
The GVHD prophylaxis regimen consists of:
Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL.
Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day -3 until Day 35
Reduced intensity conditioning (RIC) blood or marrow transplantation (BMT) has allowed older and less clinically fit patients to receive potentially curative treatment with allogeneic HCT for high risk or advanced hematological malignancies. Patients lacking an HLA-matched sibling may receive a graft from a suitably HLA-matched unrelated donor. However, up to a third of patients will not have an HLA-matched sibling or a suitably matched adult unrelated donor (i.e., no more than a mismatch at a single locus). Even when a suitably matched unrelated donor is identified, data from the National Marrow Donor Program (NMDP) indicate that a median of four months is required to complete searches that result in transplantation; thus, some number of patients succumb to their disease while awaiting identification and evaluation of a suitably matched adult unrelated donor.
Single or dual center studies have shown that partially HLA-mismatched related bone marrow (haplo-BM) and unrelated double umbilical cord blood (dUCB) are valuable sources of donor cells for RIC HCT, thus extending this treatment modality to patients who lack other donors. In order to study the reproducibility, and thus, the wider applicability of these two alternative donor strategies, The Blood and Marrow Transplantation Clinical Trials Network (BMT CTN) conducted two parallel multicenter prospective Phase II clinical trials. These two studies evaluated the safety and efficacy of related haplo-BM (BMT CTN 0603) and dUCB (BMT CTN 0604) transplantation after RIC. Both of these alternative donor approaches produced early results similar to that reported with unrelated donor, and even HLA-matched sibling, HCT. These data demonstrate not only the efficacy of both of these approaches, but also that both can be safely exported from the single center setting. Both haplo-BM and dUCB grafts can be obtained rapidly for greater than 90% of patients lacking an HLA-matched donor. This study will test the hypothesis that progression free survival at two years after RIC haplo-BM transplantation is similar to the progression free survival after RIC dUCB transplantation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01597778
|Contact: Heather Wittsackemail@example.com|
|Contact: Adam Mendizabalfirstname.lastname@example.org|
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|Study Director:||Mary Horowitz, MD, MS||Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin|