Acute Myeloid Leukemia T Cell Depletion to Improve Transplants in Adults With Acute Myeloid Leukemia (BMT CTN 0303)
Condition: Leukemia, Myelocytic, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: CD34+ selection with CliniMACS device
Intervention description: CD34+ cell selection will be performed according to procedures given in the CliniMACS Users Operating Manual and institutional Standard Operating Procedures (SOPs) in place and validated at the study sites. CliniMACS (Miltenyi device) to target CD34+ >5 x 10*6/kg and CD3+ < 1 x 10*5/kg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This study is a single arm Phase II, multicenter trial. It is designed to determine whether
      the anticipated endpoints for a T cell depleted transplant arm of a planned prospective
      randomized trial comparing T cell depleted and unmodified hematopoietic allografts are likely
      to be achieved in a multicenter study conducted by the Blood and Marrow Transplant Clinical
      Trials Network (BMT CTN or Network). The study population is patients with acute myeloid
      leukemia (AML) in first or second morphologic complete remission. The enrollment is 45
      patients.

      Based on published results of unmodified transplants from HLA-matched siblings applied to
      patients with AML in first or second morphologic complete remission, a significant
      improvement in results with a graft modified as specified in this protocol would be expected
      if disease-free survival (DFS) at 6 months was greater than 75%, the true incidence of
      transplant-related mortality at 1 year was less than 30%, and the DFS rate at 2 years was
      greater 70% for patients transplanted in first remission and less than 60% for patients
      transplanted in second remission. Additional secondary endpoints include the following: graft
      failure rate and incidences of acute grade II-IV and chronic graft-versus-host disease
      (GVHD). Additionally, the trial will have target specific doses of CD34+ progenitors and CD3+
      T cells to be obtained following fractionation with the CliniMACS system. Based on the
      results of this trial, a Phase III trial comparing T cell depleted peripheral blood stem cell
      transplants (PBSCT) with unmanipulated bone marrow or unmanipulated PBSCT will be designed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with AML with or without prior history of myelodysplastic syndrome based on
             the World Health Organization criteria at the following stages:

               -  First morphologic complete remission (CR)

               -  Second morphologic CR

          -  If prior history of central nervous system (CNS) involvement, no evidence of active
             CNS leukemia during the pre-transplant evaluation (no evidence of leukemic blasts in
             cerebrospinal fluid)

          -  First or second CR was achieved after no more than two cycles of induction (or
             re-induction for patients in second CR) chemotherapy

          -  No more than 6 months elapsed from documentation of CR to transplant for patients in
             first CR, or 3 months for patients in second CR.

          -  A 6/6 HLA antigen (A, B, DRB1)-compatible sibling donor; the match may be determined
             at serologic level for HLA-A and HLA-B loci; DRB1 must be matched at least at
             low-resolution using DNA typing techniques; HLA-C will be typed at the serologic
             level, but not included in the match algorithm

          -  Karnofsky performance status greater than 70%

          -  Life expectancy greater than 8 weeks

          -  Diffusing capacity of the lung for carbon monoxide (DLCO) of at least 40% (corrected
             for hemoglobin) with no symptomatic pulmonary disease

          -  Left ventricular ejection fraction (LVEF) by Multi Gated Acquisition Scan (MUGA) or
             echocardiogram greater than 40%

          -  Serum creatinine greater than 2 mg/dL, bilirubin greater than 2 mg/dL, and alanine
             aminotransferase (ALT) and aspartate aminotransferase (AST) levels at least 3 times
             the upper limit of normal at time of enrollment

          -  Willingness of both the patient and the donor to participate

        Exclusion Criteria:

          -  M3-AML (acute promyelocytic leukemia) in first CR

          -  Acute leukemia following blast transformation of prior chronic myelogenous leukemia
             (CML) or other myeloproliferative disease

          -  M4Eo-AML with inv 16 in first CR

          -  AML with t(8;21) in first CR

          -  Participation in other clinical trials that involve investigational drugs or devices
             except with permission from the Medical Monitor

          -  Evidence of active Hepatitis B or C infection or evidence of cirrhosis

          -  HIV positive

          -  Uncontrolled diabetes mellitus

          -  If proven or probable invasive fungal infection, infection must be controlled;
             patients may be on prophylactic anti-fungal agents, but are not permitted to be on
             anti-fungal agents for therapeutic purposes (i.e., active treatment for disease)

          -  Uncontrolled viral or bacterial infection (currently taking medication without
             clinical improvement)

          -  Documented allergy to iron dextran or murine proteins

          -  Pregnant or breastfeeding; women of childbearing age must avoid becoming pregnant
             while in the study

          -  Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)