Clinical trial NCT02458235: Donor Lymphocyte Infusion With Azacitidine to Prevent Hematologic Malignancy Relapse After Stem Cell Transplantation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myelogenous Leukemia
Acute Lymphoid Leukemia
Juvenile Myelomonocytic Leukemia
Myelodysplastic Syndrome
Keywords: pediatric leukemia myelodysplastic syndrome azacitidine
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Hellman Foundation
First posted: 2015-06-01
Enrollment: 17
Sex: ALL
Maximum age (years): 29
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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%

Primary outcomes:
measure: Relapse Rate
timeFrame: Up to 2 years
measure: Frequency of System Specific Grade 3 or Higher Treatment-related Adverse Events
timeFrame: Up to 2 years
measure: Proportion of Participants With Acute and Chronic Graft Versus Host Disease (GVHD)
timeFrame: Up to 2 years
measure: Proportion of Participants With Serious Infection
timeFrame: Up to 2 years
measure: Proportion of Participants With Severe Hematologic Toxicity Including Graft Failure
timeFrame: Up to 2 years
measure: Number of Participants Whom Had >2 Dose Reductions for Any Reason
timeFrame: Up to 2 years
Secondary outcomes:
measure: Median Relapse-free Survival
timeFrame: Up to 2 years
measure: Median Time to Relapse
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Christopher C Dvorak, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Justin T. Wahlstrom, Biljana N. Horn, Carol Fraser-Browne, Rebecca Hoeweler, Ying Lu, Alexis Melton, Jennifer Willert, Christopher C. Dvorak; Azacitidine Administration Following Hematopoietic Stem Cell Transplantation Is Safe and Feasible in Children with Acute Leukemia. Blood 2016; 128 (22): 4805. https://doi.org/10.1182/blood.V128.22.4805.4805