Clinical Trials /

Double Cord Versus Haploidentical (BMT CTN 1101)

NCT01597778

Description:

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.

Related Conditions:
  • Acute Biphenotypic Leukemia
  • Acute Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Acute Undifferentiated Leukemia
  • Adult T-Cell Leukemia/Lymphoma
  • Burkitt Lymphoma
  • Lymphoma
  • Prolymphocytic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Double Cord Versus Haploidentical (BMT CTN 1101)
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: BMTCTN1101
  • SECONDARY ID: 2U10HL069294-11
  • SECONDARY ID: 5U24CA076518
  • NCT ID: NCT01597778

Conditions

  • Acute Lymphocytic Leukemia
  • Acute Myelogenous Leukemia
  • Burkitt's Lymphoma
  • Follicular Lymphoma
  • Hodgkin Lymphoma
  • Mantle Cell Lymphoma
  • Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
Haploidentical Bone Marrow TransplantHaploidentical Bone Marrow Transplant
Double Umbilical Cord Blood TransplantDouble Umbilical Cord Blood Transplant

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Haploidentical Bone Marrow TransplantExperimentalParticipants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
    Double Umbilical Cord Blood TransplantExperimentalParticipants will receive a double umbilical cord blood transplant using a reduced intensity conditioning regimen.

      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.
            
      Maximum Eligible Age:70 Years
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Progression Free Survival (PFS)
      Time Frame:Year 2
      Safety Issue:
      Description: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.

      Secondary Outcome Measures

      Measure:Neutrophil Recovery
      Time Frame:Day 56
      Safety Issue:
      Description: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.
      Measure:Primary Graft Failure
      Time Frame:Day 56
      Safety Issue:
      Description:Primary graft failure is defined as less than 5% donor chimerism on all measurements up to and including Day 56.
      Measure:Secondary Graft Failure
      Time Frame:Day 100
      Safety Issue:
      Description: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.
      Measure:Platelet Recovery
      Time Frame:Days 100 and 180
      Safety Issue:
      Description: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.
      Measure:Donor Cell Engraftment
      Time Frame:Day 56
      Safety Issue:
      Description: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).
      Measure:Acute Graft-versus-Host Disease (aGVHD)
      Time Frame:Year 3
      Safety Issue:
      Description: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.
      Measure:Chronic Graft-versus-Host Disease (cGHVD)
      Time Frame:Year 3
      Safety Issue:
      Description: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.
      Measure:Overall Survival
      Time Frame:Year 3
      Safety Issue:
      Description: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.
      Measure:Treatment-related Mortality (TRM)
      Time Frame:Year 1 and 2
      Safety Issue:
      Description:The cumulative incidence of TRM will be estimated, event for this endpoint is death without evidence of disease progression or recurrence.
      Measure:Infections
      Time Frame:Year 3
      Safety Issue:
      Description:All Grade 2 and 3 infections will be reported.

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Medical College of Wisconsin

      Trial Keywords

      • Haplo identical transplant
      • Cord blood transplant
      • Reduced intensity conditioning regimen
      • Lymphoma
      • Leukemia

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