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

NCT ID: NCT02458235

Last Updated: 2020-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-02
• Study Completion Date: 2019-03-15

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Azacitidine/donor lymphocyte infusion

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.

Group Type: EXPERIMENTAL

azacitidine

Intervention Type: DRUG

40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals

donor lymphocyte infusion

Intervention Type: BIOLOGICAL

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.

Interventions

azacitidine

40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals

Intervention Type: DRUG

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Vidaza®, Ladakamycin

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%

• Maximum Eligible Age: 29 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hellman Foundation

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher C Dvorak, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California San Francisco

San Francisco, California, United States

Countries

United States

References

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

Reference Type: RESULT

Provided Documents

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2015-02240

Identifier Type: REGISTRY

Identifier Source: secondary_id

140813

Identifier Type: -

Identifier Source: org_study_id