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Completed

NCT Number: NCT02458235

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

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).

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Key information

Conditions

Acute Myelogenous Leukemia Acute Lymphoid Leukemia Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Juvenile Myelomonocytic Leukemia Leukemia Leukemia, Lymphoid Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Myelomonocytic, Juvenile Lymphatic Diseases Lymphoproliferative Disorders Myelodysplastic Syndrome Myelodysplastic Syndromes Myelodysplastic-Myeloproliferative Diseases Neoplasms Neoplasms by Histologic Type Precursor Cell Lymphoblastic Leukemia-Lymphoma

Age range

Up to 29 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of California San Francisco

San Francisco, California, 94143, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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%

Treatment and study plan

Azacitidine

Drug

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

Other names: Vidaza®, Ladakamycin

donor lymphocyte infusion

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.

Primary outcomes

  1. Relapse Rate

    Time frame: Up to 2 years

    Relapse rate will be estimated using a percentage of participants who relapsed. It is assumed that the rate of relapse in pediatric acute leukemia post-transplant would be 40%, azacitidine +/- Donor Lymphocyte Infusion (DLI) would reduce the 2-year relapse rate by approximately 40% to a rate of 25%.

  2. Frequency of System Specific Grade 3 or Higher Treatment-related Adverse Events

    Time frame: Up to 2 years

    Frequency of system specific adverse events of interest include renal, hepatic, cardiac, pulmonary, or neurologic toxicities. Toxicities will be graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  3. Proportion of Participants With Acute and Chronic Graft Versus Host Disease (GVHD)

    Time frame: Up to 2 years

    Proportion of participants with Grade 3-4 acute GVHD and moderate to severe chronic GVHD will be reported.

  4. Proportion of Participants With Serious Infection

    Time frame: Up to 2 years

    The proportion of participants will be reported for Grade 3-4 invasive fungal infection or disease caused by viral infections

  5. Proportion of Participants With Severe Hematologic Toxicity Including Graft Failure

    Time frame: Up to 2 years

    The proportion of participants will be reported for Grade 4 severe hematologic toxicities including graft failure

  6. Number of Participants Whom Had >2 Dose Reductions for Any Reason

    Time frame: Up to 2 years

    The number of participants whom had greater than 2 dose reductions for any reason.

Secondary outcomes

  1. Median Relapse-free Survival

    Time frame: Up to 2 years

    Release-free survival rate is defined as the median length of time after beginning treatment that the participant survives without progression or relapse, reported in months

  2. Median Time to Relapse

    Time frame: Up to 2 years

    Time to relapse is defined as the length of time after beginning treatment until the participant has experienced a relapse in disease, measured in months.

Sponsors and collaborators

Lead sponsor

University of California, San Francisco

Other

Collaborators

  • Hellman Foundation

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2019
Study completion
2019
First posted
Jun 1, 2015
Registry last updated
Oct 12, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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