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Extended vs Short-term Abatacept Dosing for Graft Versus Host Disease Prophylaxis

ConditionGraft Vs Host Disease
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age2+
SponsorBoston Children's Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Must have a hematologic malignancy treatable by HCT (except for those stipulated below under study

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Placebo

    Drug

    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.

  • Abatacept

    Drug

    Investigational prophylaxis with extended-dosing abatacept, a calcineurin inhibitor and methotrexate.

Treatment groups

160 Participants
are divided into 2 treatment groups
Group A: Standard GVHD Prophylaxis + Abatacept + PlaceboPlacebo comparator 2 interventions
Group B: Standard GVHD Prophylaxis + Abatacept Extended dosingExperimental treatment 1 intervention

Trial outcomes

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.

Time frame
2 years

Secondary outcomes

1

Severe Chronic GVHD

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.

Time frame
2 years
2

Relapse-Free survival

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.

Time frame
2 years
3

Non-relapse mortality

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.

Time frame
2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Boston Children's Hospital

Lead sponsor

Bristol-Myers Squibb

Collaborator

Source ClinicalTrials.gov
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