Abatacept Extended Dosing Compared to Abatacept Short-Term Dosing for the Prevention of Graft versus Host Disease, ABA3 Study
Hematopoietic Malignancies
2 Years and older, Male and Female
20-227 (primary)
NCI-2022-03010
Summary
This phase II trial compares the effect of extended abatacept dose to short term abatacept dose given in combination with a calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate in preventing graft versus host disease (GVHD) after bone marrow transplant in patients with blood cancers. Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft versus host disease). Abatacept is a immunomodulator drug that works to decrease the body's immune response by blocking the activation of T-cells (immune cells) to prevent bone marrow rejection and GVHD. Tacrolimus, cyclosporine, and methotrexate are standard of care drugs given after transplant to help prevent GVHD. Tacrolimus and cyclosporine are in a class of medications called immunosupressants. They work by decreasing the activity of the immune system to prevent it from attacking the transplant. Methotrexate is in a class of medications called antimetabolites. Methotrexate may help prevent GVHD by decreasing the activity of the immune system. Giving abatacept in combination with a calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate after the transplant may help prevent graft versus host disease.
Objectives
PRIMARY OBJECTIVE:
I. To determine whether an 8-dose regimen of abatacept will improve the rate of severe (grade III-IV) acute GVHD (AGVHD)-free, severe chronic GVHD (CGVHD)-free, relapse-free survival (‘SGRFS’) compared to a 4-dose regimen, during human leukocyte antigen unrelated-donor hematopoietic stem cell transplantation (HCT) for patients with hematologic malignancies.
OUTLINE: Patients are randomized into 1 of 5 groups.
GROUP A: Patients receive abatacept intravenously (IV) on days 1, 5, 14 and 28, and placebo IV on days 60, 90, 120, 150. Patients also receive methotrexate IV on days 1, 3, 6 and 11, and either tacrolimus or cyclosporine on days -2 to 180.
GROUP B: Patients receive abatacept IV on days 1, 5, 14, 28, 60, 90, 120, and 150. Patients also receive methotrexate IV on days 1, 3, 6 and 11, and either tacrolimus or cyclosporine on days -2 to 180.
GROUP C: Patients receive abatacept IV on days 1,5,14 and 28. Patients also receive methotrexate IV on days 1, 3, 6 and 11, and either tacrolimus or cyclosporine on days -2 to 180.
GROUP D: Patients receive abatacept IV on days 1,5,14 and 28 and receive placebo IV on days 60, 90, 120 and 150. Patients also receive methotrexate IV on days 1, 3, 6 and 11, and either tacrolimus or cyclosporine on days -2 to 180.
GROUP E: Patients receive abatacept IV on days 1,5,14, 28, 60, 90, 120 and 150. Patients also receive methotrexate IV on days 1, 3, 6 and 11, and either tacrolimus or cyclosporine on days -2 to 180.
Eligibility
- Must be at least 2 years old and weigh 10 kg. Enrollment of patients age 2-<6 will be suspended after 5 enrolled and treated patients and will only resume after Data and Safety Monitoring Committee (DSMC) review and approval.
- Must have a willing unrelated 8/8 or 7/8 matched 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 exclusion criteria), which is in remission by standard testing (no patients in relapse will be included).
- Karnofsky performance score or Lansky Play-Performance Scale score >= 80.
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