Double Cord Versus Haploidentical (BMT CTN 1101)
Condition: Acute Lymphocytic Leukemia; Acute Myelogenous Leukemia; Burkitt's Lymphoma; Follicular Lymphoma; Hodgkin Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin Lymphoma
MeSH terms: Burkitt Lymphoma; Lymphoma; Leukemia; Leukemia, Myeloid; Lymphoma, Mantle-Cell; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
Study type: Interventional
Phase: Phase 3

Summary: 
      Hematopoietic cell transplants (HCT)are one treatment option for people with leukemia or
      lymphoma. Family members,unrelated donors or banked umbilical cordblood units with similar
      tissue type can be used for HCT. This study will compare the effectiveness of two new types
      of bone marrow transplants in people with leukemia or lymphoma: one that uses bone marrow
      donated from family members with only partially matched bone marrow; and, one that uses two
      partially matched cord blood units.
    

Detailed description: 
      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.
    

Intervention name(s): Haploidentical Bone Marrow Transplant; Double Umbilical Cord Blood Transplant
Intervention type(s): Biological; Biological
Intervention description(s): 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; 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
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Haplo identical transplant; Cord blood transplant; Reduced intensity conditioning regimen; Lymphoma; Leukemia