Graft Vs Host Disease
Conditions
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.
Interventions
DRUGPlacebo
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.
DRUGAbatacept
Investigational prophylaxis with extended-dosing abatacept, a calcineurin inhibitor and methotrexate.
Sponsors
Boston Children's Hospital
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Must be at least 2 years old and weigh 10 kg. 2. 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. 3. 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. 4. Must have a hematologic malignancy treatable by HCT (except for those stipulated below under study
Exclusion criteria
), which is in remission by standard testing (no patients in relapse will be included). 5. 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. 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severe AGVHD-free, severe CGVHD-free, relapse-free survival (SGRFS) | 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severe Chronic GVHD | 2 years | We will compare the cause-specific hazards of severe chronic GVHD, including overlap syndrome (based on adjudicated events), using the NIH consensus criteria, between the two arms of the study. |
| Relapse-Free survival | 2 years | We will compare the hazards of failure (earliest of relapse or any-cause death) for relapse-free survival (RFS), which will be defined as survival without relapse of underlying malignancy. |
| Non-relapse mortality | 2 years | We will compare the cause-specific hazards of non-relapse mortality (NRM), which will be defined as death without a prior relapse, with relapse defined as either morphological or standard cytogenetic evidence of acute leukemia or MDS consistent with pre-transplant features, or radiologic evidence of lymphoma, documented or not by biopsy. |
Countries
United States
Contacts
CONTACTBrandi M Bratrude, BA
Outcome results
None listed