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
Intervention: Haploidentical Bone Marrow Transplant; Double Umbilical Cord Blood Transplant
Intervention description: 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
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 368.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Haplo identical transplant; Cord blood transplant; Reduced intensity conditioning regimen; Lymphoma; Leukemia

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients 18 to 70 years old

          -  Patients must have available both: a)One or more potential related mismatched donors
             (biologic parent(s) or siblings (full or half) or children). At least low resolution
             DNA based human leukocyte antigen (HLA) typing at HLA-A, -B, and -DRB1 for potential
             haploidentical sibling donors is required. b)At least two potential umbilical cord
             blood units identified. Each unit must have a minimum of 1.5 x 10^7/kg
             pre-cryopreserved total nucleated cell dose. For non-red blood cell depleted units,
             the minimum pre-cryopreserved total nucleated cell dose of each unit must be at least
             2.0 x 10^7/kg. Units must be HLA matched at a minimum of 4/6 to the recipient at
             HLA-A, HLA-B (at low resolution using DNA based typing) and HLA-DRB1 (at high
             resolution using DNA based typing). Confirmatory typing is not required for
             randomization.

          -  Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR1) that is NOT
             considered favorable-risk as defined by the presence of at least one of the following:
             Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), other Mixed Lineage Leukemia
             (MLL) rearrangements; White blood cell counts of greater than 30,000/mcL (B-ALL) or
             greater than 100,000/mcL (T-ALL)at diagnosis; Recipient age older than 30 years at
             diagnosis; Time to CR greater than 4 weeks

          -  Acute Myelogeneous Leukemia (AML) in CR1 that is NOT considered as favorable-risk.
             Favorable risk is defined as having one of the following: t(8.21) without CKIT
             mutation, inv(16) without CKIT mutation or t(16;16), normal karyotype with mutated
             NPM1 and not FLT-ITD, normal karyotype with double mutated CEBPA, Acute promyelocytic
             leukemia (APL) in first molecular remission at end of consolidation

          -  Acute Leukemias in 2nd or subsequent CR

          -  Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR,
             adult T-cell leukemia/lymphoma in first or subsequent CR

          -  Burkitt's lymphoma: second or subsequent CR

          -  Lymphoma fulfilling the following criteria: Chemotherapy-sensitive (at least stable
             disease lymphomas that have failed at least 1 prior regimen of multi-agent
             chemotherapy and are INELIGIBLE for an autologous transplant. Patients with chronic
             lymphocytic leukemia (CLL) are not eligible regardless of disease status.

          -  Performance status: Karnofsky score greater than or equal to 70%.

        Additional Patient Inclusion Criteria for Conditioning:

          -  Patients with Adequate Physical Function as Measured by: a. Cardiac: Left ventricular
             ejection fraction at rest must be greater than or equal to 40%, or shortening fraction
             less than 25%; b. Hepatic: Bilirubin less than or equal to 2.5 mg/dL, except for
             patients with Gilbert's syndrome or hemolysis. Alanine aminotransferase (ALT),
             aspartate aminotransferase (AST), and Alkaline Phosphatase less than 5 x upper limit
             of normal; c. Renal: Serum creatinine within normal range, or if serum creatinine
             outside normal range, then renal function (measured or estimated creatinine clearance
             or GFR)greater than 40 mL/min/1.73m^; d. Pulmonary: Diffusing capacity of the lung for
             carbon monoxide (DLCO) (corrected for hemoglobin), forced expiratory volume in one
             second (FEV1), and forced vital capacity (FVC) greater than 50% predicted;

          -  Additional Patient Inclusion Criteria for Patients Assigned to Haploidentical BM Arm:
             Patients must be HLA typed at high resolution using DNA based typing at the following
             HLA-loci: HLA-A, -B, -C and DRB1 and have available a related haploidentical BM donor
             with 2, 3, or 4 HLA-mismatches. A unidirectional mismatch in either the graft versus
             host or host versus graft direction is considered a mismatch. The donor and recipient
             must be HLA identical for at least one antigen (using high resolution DNA based
             typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1. Fulfillment
             of this criterion shall be considered sufficient evidence that the donor and recipient
             share one HLA haplotype, and typing of additional family members is not required.

          -  Additional Patient Inclusion Criteria for Patients Assigned to Double Umbilical Cord
             Blood Arm:

               1. Patients must have available two UCB units fulfilling the following criteria:

                    1. Each unit must have a minimum of 1.5 x 10^7/kg pre-cryopreserved total
                       nucleated cell dose. For non-red blood cell depleted units, the minimum
                       pre-cryopreserved total nucleated cell dose of each unit must be at least
                       2.0 x10^7/kg.

                    2. Units must be HLA matched at a minimum of 4/6 to the recipient at HLA -A,
                       HLA-B (at low resolution using DNA based typing), and HLA -DRB1 (at high
                       resolution using DNA based typing).

                    3. Additional graft selection criteria specified in section 2.5

               2. Patients must have received at least one cycle of the cytotoxic chemotherapy
                  regimens (or regimen of similar intensity) listed in Appendix D within 3 months
                  of enrollment (measured from the start date of chemotherapy) OR have had an
                  autologous transplant within 24 months of enrollment OR receive 300 cGy as part
                  of the preparative regimen

        Exclusion Criteria:

          -  Patients with suitably matched related or unrelated donor, as defined per
             institutional practice.

          -  Recipients of prior autologous hematopoietic stem cell transplantation are ineligible
             if disease recurrence occurred less than 6 months from their autologous stem cell
             transplant.

          -  Current uncontrolled bacterial, viral or fungal infection (currently taking medication
             with evidence of progression of clinical symptoms or radiologic findings).

          -  Prior allogeneic HCT.

          -  Patients with history of primary idiopathic myelofibrosis or any severe marrow
             fibrosis.

          -  Planned use of prophylactic donor lymphocyte infusion (DLI) therapy.

          -  Anti-donor HLA antibodies.

        Additional exclusion criteria:

          -  Pregnancy or breast-feeding.

          -  Evidence of HIV infection or known HIV positive serology.