Clinical Trial: Donor Lymphocyte Infusion With Azacitidine to Prevent Hematologic Malignancy Relapse After Stem Cell Transplantation

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase II Study of Risk-adapted Donor Lymphocyte Infusion and Azacitidine for the Prevention of Hematologic Malignancy Relapse Following Allogeneic Stem Cell Transplantation

Brief Summary: The goal of this study is to determine whether post-transplant consolidation with azacitidine combined with donor lymphocyte infusion (DLI) is a safe and effective approach for the prevention of relapse in pediatric and young adult patients with hematologic malignancies who have undergone hematopoietic stem cell transplantation (HSCT).

Detailed Summary: This is a phase II single-arm trial of azacitidine (IV or SC) in combination with escalating donor lymphocyte infusion (DLI). Patients will be enrolled on the study by day +28 +/- 7 post-transplant, prior to withdrawal of immunosuppression or administration of donor lymphocyte infusion (DLI). They will have donor chimerism and minimal residual disease (MRD) testing from peripheral blood (PB) and bone marrow (BM) on day +28 ± 7. Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative MRD results. Depending on risk assessment, immunosuppression will be tapered according to standard or fast schedules, and patients (with the exception of low-risk ALL patients) will receive one cycle of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days). After tapering immunosuppression, chimerism will be repeated and patients will receive up to 6 additional cycles of low-dose azacitidine, depending on risk assessment. For patients who meet criteria for high risk of relapse, azacitidine will be combined with escalating doses of DLI for a maximum of 7 cycles in total. Risk and safety assessments, including routine laboratory parameters, donor chimerism, minimal residual disease, and GHVD activity will be assessed following each cycle. Chimerism and minimal residual disease testing will be repeated every cycle by peripheral blood (PB), and bone marrow (BM) will be tested every other cycle. Patients will be followed by laboratory monitoring and physician evaluation prior to each cycle, and will be followed for two years post-transplant to study toxicity and GVHD outcomes.
Sponsor: University of California, San Francisco

Current Primary Outcome:

  • Relapse rate [ Time Frame: 2 years ]
  • Incidence of grade 3 or higher adverse events [ Time Frame: 2 years ]
    To be graded using CTCAE 4.0. Adverse events to be reported include renal, hepatic, cardiac, pulmonary, or neurologic toxicities.
  • Incidence of acute and chronic Graft versus Host Disease (GVHD) [ Time Frame: 2 years ]
    Incidence will be reported for Grade 3-4 acute GVHD and moderate to severe chronic GVHD


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Relapse-free survival rate [ Time Frame: 2 years ]
  • Median time to relapse [ Time Frame: 2 years ]
    To be measured in months.
  • Post-transplant immune reconstitution [ Time Frame: 2 years ]
    Effect of azacitidine in combination with DLI on immune function as measured by flow cytometry and proliferation to mitogen.
  • MRD detection in patients with AML [ Time Frame: 2 years ]
    In addition to conventional flow cytometry, feasibility of gene expression profiling for detection of MRD in AML will be used.


Original Secondary Outcome: Same as current

Information By: University of California, San Francisco

Dates:
Date Received: January 5, 2015
Date Started: June 2015
Date Completion: December 2017
Last Updated: May 18, 2016
Last Verified: May 2016