Extended vs Short-term Abatacept Dosing for Graft Versus Host Disease Prophylaxis
ABA3
A Randomized Double-Blind Trial of Abatacept Extended Dosing Versus Abatacept Short-term Dosing for Graft Versus Host Disease Prophylaxis: "ABA3"
2 other identifiers
interventional
160
1 country
14
Brief Summary
This is a multicenter randomized, double blind, Phase 2 trial for patients receiving transplants from 7 of 8 HLA matched donors, in which an extended dosing regimen of abatacept, and a short-term dosing regimen + placebo, when added to standard calcineurin inhibitor + methotrexate-based prophylaxis, will be compared for their ability to improve outcomes in patients with a minimum follow-up of one year post-transplant. All patients will receive 4 doses of abatacept (Days -1, +5, +14, +28). Prior to the fifth dose, patients will be randomly assigned to the 4-dose abatacept arm and receive 4 doses of placebo or 8-dose abatacept arm and receive 4 more doses of abatacept. The primary endpoint of the study will be severe AGVHD-free, severe CGVHD-free, relapse-free survival (SGRFS). The study will end when the last patient has reached 2 years after transplant. Results will first be calculated and the study unblinded when the last patient has reached one year post-transplant.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2022
Longer than P75 for phase_2
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 5, 2020
CompletedFirst Posted
Study publicly available on registry
May 8, 2020
CompletedStudy Start
First participant enrolled
March 30, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2028
February 19, 2026
February 1, 2026
5.1 years
May 5, 2020
February 17, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Severe AGVHD-free, severe CGVHD-free, relapse-free survival (SGRFS)
SGRFS will be modeled as a time-to-event outcome, and as such, failures that occur beyond one year and before study end will be considered in the analysis.
2 years
Secondary Outcomes (3)
Severe Chronic GVHD
2 years
Relapse-Free survival
2 years
Non-relapse mortality
2 years
Study Arms (2)
Standard GVHD Prophylaxis + Abatacept + Placebo
PLACEBO COMPARATORStandard GVHD prophylaxis of calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate + 4 doses of Abatacept (investigational product) + 4 doses of Placebo.
Standard GVHD Prophylaxis + Abatacept Extended dosing
EXPERIMENTALStandard GVHD prophylaxis of calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate + 8 doses of Abatacept.
Interventions
During the extended dosing of abatacept, those randomized to receive 4 doses will receive a placebo consisting of an equal volume of normal saline solution.
Investigational prophylaxis with extended-dosing abatacept, a calcineurin inhibitor and methotrexate.
Eligibility Criteria
You may qualify if:
- Must be at least 2 years old and weigh 10 kg.
- Must have a willing unrelated adult donor (bone marrow or peripheral blood). Donors may have a single mismatch (i.e. be a 7/8) and this mismatch may be at the allele or antigen level; however, donors with allele level disparity should be given preference over those with antigen level disparity. Patients for whom a donor is available with disparity only in the host versus graft direction (because of recipient homozygosity), will not be eligible, since this mismatching does not increase the risk for GVHD. Centers may perform extended typing (e.g. DQB1 and DPB1) according to institutional practices and use these results in selecting donors; however, it is recommended that this extending typing be used only to select between donors who are equally well matched with the recipient at the A, B, C and DRB1.
- All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
You may not qualify if:
- Patients with an inherited predisposition to leukemia or otherwise hematologic malignancies that have not been associated with predisposition to transplant morbidities or non-hematologic cancers.
- Karnofsky performance score or Lanskey Play-Performance Scale score \>/= 80.
- If the patient does not meet defined eligibility requirements, the PI/study committee must be contacted to determine eligibility.
- Patients with the following hematologic malignancies will be excluded: Chronic Lymphocytic Leukemia, Myeloma and Primary Myelofibrosis.
- Active Relapse (\>5% blasts) of their primary malignancy.
- For patients with Acute Lymphocytic Leukemia (ALL) with pre-transplant MRD testing performed as standard practice at the treating institution, patients with MRD \>0.01% will be ineligible.
- For patients with Acute Myeloid Leukemia (AML) with pre-transplant MRD testing as standard of practice at the treating institution, patients with any MRD status are eligible and should be enrolled at the discretion of provider.
- For patients with MDS, those with \>5% blasts will be excluded.
- Prior allogeneic HCT.
- Uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment.
- HIV infection.
- Serious psychiatric disease including schizophrenia, bipolar disorder and severe depression.
- Prisoners or others who are compulsorily detained.
- Any patient with a known or suspected inherited predisposition to cancer should be discussed with the study team prior to screening for eligibility.
- Patients with a known inherited or constitutional predisposition to transplant morbidities, including, but not limited to Fanconi Anemia, Dyskeratosis Congenita, Shwachman-Diamond Syndrome and Down Syndrome will be excluded.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Boston Children's Hospitallead
- Bristol-Myers Squibbcollaborator
Study Sites (14)
City Of Hope National Medical Center
Duarte, California, 91010, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University/Winship Cancer Center
Atlanta, Georgia, 30322, United States
University of Chicago
Chicago, Illinois, 60637, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Washington University St. Louis
St Louis, Missouri, 63110, United States
University of Rochester
Rochester, New York, 14642, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229, United States
Oregon Health and Sciences University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director, Stem Cell Transplantation Program, Division of Hematology/Oncology, Boston Children's Hosptial
Study Record Dates
First Submitted
May 5, 2020
First Posted
May 8, 2020
Study Start
March 30, 2022
Primary Completion (Estimated)
May 1, 2027
Study Completion (Estimated)
June 1, 2028
Last Updated
February 19, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data can be shared no earlier that 1 year following the date of publication.
- Access Criteria
- Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu
The Dana-Farber/Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscripts may only be shared under the terms of a Data Use Agreement. Requests may be directed to aba3study@childrens.harvard.edu. The protocol and statistical analysis plan will be made available on clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.