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

University of California San Francisco (UCSF)

Status and phase: Completed; Phase 2

Conditions: Acute Myelogenous Leukemia; Acute Lymphoid Leukemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndrome

Treatments: Biological: donor lymphocyte infusion; Drug: azacitidine

Study type: Interventional

Funder types: Other

Identifiers

NCT02458235

140813

NCI-2015-02240 (Registry Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 17 patients

Sex: All

Ages: Under 29 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients age 0 - 29.9 years undergoing allogeneic peripheral blood stem cell transplant
• Patients with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL)
• Patients with juvenile myelomonocytic leukemia (JMML)
• Patients with myelodysplastic syndrome (MDS)

Exclusion criteria

• Patients who have had a prior transplant.
• Patients with Fanconi anemia or other cancer-predisposition syndromes
• Patients with expected survival <12 weeks
• Lansky score <60%

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 1 patient group

Azacitidine/donor lymphocyte infusion

Experimental group

Description:

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 Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI.

Treatment:

Drug: azacitidine

Biological: donor lymphocyte infusion