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

Phase 2

Recruiting

• Conditions: Graft Vs Host Disease

• Registration Number: NCT04380740
• Lead Sponsor: Boston Children's Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-5-5
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

Inclusion Criteria:<br><br> 1. Must be at least 2 years old and weigh 10 kg.<br><br> 2. Must have a willing unrelated adult donor (bone marrow or peripheral blood). Donors<br> may have a single mismatch (i.e. be a 7/8) and this mismatch may be at the allele or<br> antigen level; however, donors with allele level disparity should be given<br> preference over those with antigen level disparity. Patients for whom a donor is<br> available with disparity only in the host versus graft direction (because of<br> recipient homozygosity), will not be eligible, since this mismatching does not<br> increase the risk for GVHD. Centers may perform extended typing (e.g. DQB1 and DPB1)<br> according to institutional practices and use these results in selecting donors;<br> however, it is recommended that this extending typing be used only to select between<br> donors who are equally well matched with the recipient at the A, B, C and DRB1.<br><br> 3. All patients and/or their parents or legal guardians must sign a written informed<br> consent. Assent, when appropriate, will be obtained according to institutional<br> guidelines.<br><br> 4. Must have a hematologic malignancy treatable by HCT (except for those stipulated<br> below under study Exclusion Criteria), which is in remission by standard testing (no<br> patients in relapse will be included).<br><br> 5. Patients with an inherited predisposition to leukemia or otherwise hematologic<br> malignancies that have not been associated with predisposition to transplant<br> morbidities or non-hematologic cancers.<br><br> 6. Karnofsky performance score or Lanskey Play-Performance Scale score >/= 80.<br><br> - If the patient does not meet defined eligibility requirements, the PI/study<br> committee must be contacted to determine eligibility.<br><br>Exclusion Criteria:<br><br> 1. Patients with the following hematologic malignancies will be excluded: Chronic<br> Lymphocytic Leukemia, Myeloma and Primary Myelofibrosis.<br><br> 2. Active Relapse (>5% blasts) of their primary malignancy.<br><br> 3. For patients with Acute Lymphocytic Leukemia (ALL) with pre-transplant MRD testing<br> performed as standard practice at the treating institution, patients with MRD >0.01%<br> will be ineligible.<br><br> 4. For patients with Acute Myeloid Leukemia (AML) with pre-transplant MRD testing as<br> standard of practice at the treating institution, patients with any MRD status are<br> eligible and should be enrolled at the discretion of provider.<br><br> 5. For patients with MDS, those with >5% blasts will be excluded.<br><br> 6. Prior allogeneic HCT.<br><br> 7. Uncontrolled viral, bacterial, fungal or protozoal infection at the time of study<br> enrollment.<br><br> 8. HIV infection.<br><br> 9. Serious psychiatric disease including schizophrenia, bipolar disorder and severe<br> depression.<br><br> 10. Prisoners or others who are compulsorily detained.<br><br> 11. Any patient with a known or suspected inherited predisposition to cancer should be<br> discussed with the study team prior to screening for eligibility.<br><br> 1. Patients with a known inherited or constitutional predisposition to transplant<br> morbidities, including, but not limited to Fanconi Anemia, Dyskeratosis<br> Congenita, Shwachman-Diamond Syndrome and Down Syndrome will be excluded.<br><br> 2. Patients with known inherited or constitutional predisposition to<br> non-hematologic cancers including, but not limited to Li-Fraumeni syndrome,<br> BRCA1 and BRCA2 mutations will be excluded.<br><br> 12. Patients with active non-hematological malignancies (except non-melanoma skin<br> cancers) or those with non-hematological malignancies (except non-melanoma skin<br> cancers) who have been rendered with no evidence of disease, and are disease free<br> for <2 years.<br><br> 13. Incompletely treated active tuberculosis Infection.<br><br> 14. Pregnancy (positive serum b-HCG) or breastfeeding.<br><br> 15. Estimated GFR of < 50 mL/min/1.73m2.<br><br> 16. Cardiac ejection fraction < 50 (using M-Mode if assessment is done by ECHO)<br><br> 17. T.bilirubin > 2 × upper limit of normal or ALT > 4 × upper limit of normal or<br> unresolved veno-occlusive disease.<br><br> 18. Pulmonary disease with FVC, FEV1 or DLCO parameters <45% predicted (corrected for<br> hemoglobin) or requiring supplemental oxygen. Children who are developmentally<br> unable to perform pulmonary function testing will be assessed solely on their need<br> for supplemental oxygen.<br><br> 19. Presence of antibodies to a mismatched donor HLA antigen (please refer to Section<br> 3.4.g).<br><br> 20. Patients who have developed severe AGVHD, severe CGVHD or relapse will be excluded<br> at the time of randomization.<br><br> 21. Exclusion Criteria Prior to Randomization (prior to 5th dose of abatacept/placebo):<br><br> 1. Severe allergic reaction during the first 4 doses of abatacept<br><br> 2. If any clinical events occur that preclude further dosing of abatacept, those<br> patients will be deemed ineligible for randomization

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Severe AGVHD-free, severe CGVHD-free, relapse-free survival (SGRFS)

Secondary Outcome Measures

Name	Time	Method
Severe Chronic GVHD;Relapse-Free survival;Non-relapse mortality