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Extended versus short abatacept dosing to prevent graft-versus-host disease after mismatched unrelated donor transplant

A Randomized Double-Blind Trial of Abatacept Extended Dosing Versus Abatacept Short-term Dosing for Graft Versus Host Disease Prophylaxis: "ABA3"

Phase 2 Interventional Boston Children's Hospital · NCT04380740

This trial tests whether giving extra abatacept doses after a 7/8 matched unrelated donor stem cell transplant helps prevent severe acute and chronic graft-versus-host disease in patients already receiving standard calcineurin inhibitor plus methotrexate prophylaxis.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment160 (estimated)
Ages2 Years and up
SexAll
SponsorBoston Children's Hospital Academic / other
Drugs / interventionsmethotrexate
Locations15 sites (Duarte, California and 14 other locations)
Trial IDNCT04380740 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, double-blind Phase 2 trial comparing an extended abatacept dosing schedule to a short-term schedule plus placebo in patients receiving largely 7/8 HLA matched unrelated donor hematopoietic stem cell transplants. All participants receive four initial abatacept doses around the time of transplant, then are randomized to receive either four additional abatacept doses or four placebo doses added to standard calcineurin inhibitor plus methotrexate prophylaxis. The primary endpoint is severe acute and chronic GVHD-free, relapse-free survival (SGRFS) with at least one year of follow-up for primary analysis and two years total follow-up for all patients. The trial is conducted at several major U.S. transplant centers and will remain blinded until the pre-specified one-year analysis is complete.

Who should consider this trial

Good fit: Ideal candidates are patients aged 2 years or older (≥10 kg) who have a willing unrelated adult donor (including single-allele mismatches) and are scheduled to receive calcineurin inhibitor plus methotrexate GVHD prophylaxis and can provide informed consent or assent.

Not a fit: Patients without an unrelated donor, those receiving markedly different GVHD prophylaxis regimens, or those whose donor mismatch is only in the host-versus-graft direction (recipient homozygosity) are unlikely to benefit from this specific protocol.

Why it matters

Potential benefit: If successful, the extended abatacept regimen could reduce severe acute and chronic GVHD and improve relapse-free survival after mismatched unrelated donor transplants.

How similar studies have performed: Early-phase and non-randomized studies of abatacept added to standard prophylaxis have shown promising reductions in GVHD after mismatched unrelated donor transplants, but randomized evidence is limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Exclusion Criteria:

1. Patients with the following hematologic malignancies will be excluded: Chronic Lymphocytic Leukemia, Myeloma and Primary Myelofibrosis.
2. Active Relapse (\>5% blasts) of their primary malignancy.
3. 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.
4. 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.
5. For patients with MDS, those with \>5% blasts will be excluded.
6. Prior allogeneic HCT.
7. Uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment.
8. HIV infection.
9. Serious psychiatric disease including schizophrenia, bipolar disorder and severe depression.
10. Prisoners or others who are compulsorily detained.
11. Any patient with a known or suspected inherited predisposition to cancer should be discussed with the study team prior to screening for eligibility.

    1. 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.
    2. Patients with known inherited or constitutional predisposition to non-hematologic cancers including, but not limited to Li-Fraumeni syndrome, BRCA1 and BRCA2 mutations will be excluded.
12. Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, and are disease free for \<2 years.
13. Incompletely treated active tuberculosis Infection.
14. Pregnancy (positive serum b-HCG) or breastfeeding.
15. Estimated GFR of \< 50 mL/min/1.73m2.
16. Cardiac ejection fraction \< 50 (using M-Mode if assessment is done by ECHO)
17. T.bilirubin \> 2 × upper limit of normal or ALT \> 4 × upper limit of normal or unresolved veno-occlusive disease.
18. Pulmonary disease with FVC, FEV1 or DLCO parameters \<45% predicted (corrected for hemoglobin) or requiring supplemental oxygen. Children who are developmentally unable to perform pulmonary function testing will be assessed solely on their need for supplemental oxygen.
19. Presence of antibodies to a mismatched donor HLA antigen (please refer to Section 3.4.g).
20. Patients who have developed severe AGVHD, severe CGVHD or relapse will be excluded at the time of randomization.
21. Exclusion Criteria Prior to Randomization (prior to 5th dose of abatacept/placebo):

    1. Severe allergic reaction during the first 4 doses of abatacept
    2. If any clinical events occur that preclude further dosing of abatacept, those patients will be deemed ineligible for randomization

Where this trial is running

Duarte, California and 14 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Graft Vs Host Disease
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.