- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02458235
Donor Lymphocyte Infusion With Azacitidine to Prevent Hematologic Malignancy Relapse After Stem Cell Transplantation
October 9, 2020 updated by: University of California, San Francisco
A Phase II Study of Risk-adapted Donor Lymphocyte Infusion and Azacitidine for the Prevention of Hematologic Malignancy Relapse Following Allogeneic 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).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
17
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
San Francisco, California, United States, 94143
- University of California San Francisco
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
No older than 29 years (ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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%
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 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.
|
40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals
Other Names:
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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%.
|
Up to 2 years
|
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.
|
Up to 2 years
|
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.
|
Up to 2 years
|
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
|
Up to 2 years
|
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
|
Up to 2 years
|
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.
|
Up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Up to 2 years
|
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.
|
Up to 2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Christopher C Dvorak, M.D., University of California, San Francisco
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
June 2, 2015
Primary Completion (ACTUAL)
March 15, 2019
Study Completion (ACTUAL)
March 15, 2019
Study Registration Dates
First Submitted
January 5, 2015
First Submitted That Met QC Criteria
May 27, 2015
First Posted (ESTIMATE)
June 1, 2015
Study Record Updates
Last Update Posted (ACTUAL)
October 12, 2020
Last Update Submitted That Met QC Criteria
October 9, 2020
Last Verified
October 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Myelodysplastic-Myeloproliferative Diseases
- Myelodysplastic Syndromes
- Hematologic Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Preleukemia
- Leukemia, Myelomonocytic, Juvenile
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Azacitidine
Other Study ID Numbers
- 140813
- NCI-2015-02240 (REGISTRY: University of California, San Francisco)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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