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
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      BACKGROUND:

      Allogeneic hematopoietic cell transplantation is an accepted therapy for AML. Transplants of
      unmodified HLA-matched related bone marrow or peripheral blood stem cells following
      conditioning with total body irradiation (TBI) and cyclophosphamide or VP-16 or busulfan and
      cyclophosphamide have led to sustained DFS rates of 45-60% for adults transplanted in first
      complete remission (CR1) and 40-53% for patients transplanted in second complete remission
      (CR2). In several single center and multicenter cooperative group prospective trials
      comparing HLA-matched allogeneic transplants to chemotherapy in the treatment of AML in CR1,
      DFS rates for the transplant arm were almost invariably superior; however, these advantages
      were statistically significant in only a minority of the cooperative group studies conducted.
      In each study, the risk of relapse was significantly lower for patients receiving allogeneic
      transplants. However, this advantage was counterbalanced by transplant-related mortality,
      principally reflecting infections complicating GVHD and its treatment.

      DESIGN NARRATIVE:

      Despite increased risks of infection, development of effective T cell depletion (TCD)
      techniques for prevention of GVHD and tolerable modifications of regimens for pre-transplant
      cytoreduction that secure consistent engraftment offer the potential for significant
      decreases in transplant-related mortality. Furthermore, the use of TCD transplants in the
      treatment of patients with AML is not associated with substantial increases in the incidence
      of relapse. Several single center trials indicate highly encouraging long-term results,
      particularly for patients with AML in CR1 or CR2. Although the number of cases in each single
      center series is limited, the consistency of the results suggests that the use of an
      effective technique for TCD together with an adequate cytoreductive regimen might yield
      transplant results superior to those achieved with unmodified grafts.
    

Intervention name(s): CD34+ selection with CliniMACS device
Intervention type(s): Biological
Intervention description(s): 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
Other intervention name(s): T Cell Depletion
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment