NCT02458235

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 29 Years
• Healthy volunteers: Not accepted

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 description

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.

Conditions

• Acute Myelogenous Leukemia
• Acute Lymphoid Leukemia
• Juvenile Myelomonocytic Leukemia
• Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	azacitidine	40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals
BIOLOGICAL	donor lymphocyte infusion	For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.

Timeline

• Start date: 2015-06-02
• Primary completion: 2019-03-15
• Completion: 2019-03-15
• First posted: 2015-06-01
• Last updated: 2020-10-12
• Results posted: 2020-10-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study