Incremental Eligibility Criteria for the BMT CTN 1507 Haploidentical Trial for Children with Sickle Cell Disease
Document Type
Journal Article
Publication Date
10-7-2024
Journal
Blood advances
DOI
10.1182/bloodadvances.2024014078
Abstract
The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1507 leadership and the Data Safety Monitoring Board (DSMB) established incremental entry criteria for children aged 5-14.99 years with sickle cell disease (SCD) enrolling on a phase 2 trial of HLA-haploidentical hematopoietic stem cell transplantation (clinicaltrials.gov #NCT032635590). First, enrollment was limited to overt stroke in the first 10 participants (Stage 4). Subsequently, the DSMB reviewed the interim results and expanded eligibility to include children with silent cerebral infarcts or abnormal transcranial Doppler velocities with magnetic resonance angiography-defined cerebral vasculopathy (Stage 3). A third cohort was enrolled after the DSMB reviewed the clinical outcomes in these cumulative initial enrollments (n=18). Additions to the entry criteria included non-neurologic morbidities (Stage 2). Eligibility criteria included: a) life-threatening acute chest syndrome requiring exchange transfusion, b) right heart catheterization confirmed pulmonary hypertension, c) persistent systemic hypertension despite maximum medical therapy, d) acute pain despite maximum medical therapy in the absence of psychosocial factors and unmanaged asthma after adjudication, or e) 2 major priapism episodes in 12 months or 3 in 24 months. Children with SCD who did not meet the criteria for stages 4, 3, and 2 were not eligible. For the first time, we introduce a staged strategy to eligibility for a curative therapy trial for children with SCD concordant with 45 CFR § 46.405(b). The research governance-mandated eligibility strategy used within the BMT CTN 1507 phase 2 study may apply to future pediatric SCD curative therapy trials.
APA Citation
John, Tami D.; Walters, Mark C.; Rangarajan, Hemalatha G.; Rahim, Mahvish Q.; McKinney, Christopher M.; Bollard, Catherine M.; Abusin, Ghada; Eapen, Mary; Kassim, Adetola A.; and DeBaun, Michael R., "Incremental Eligibility Criteria for the BMT CTN 1507 Haploidentical Trial for Children with Sickle Cell Disease" (2024). GW Authored Works. Paper 5865.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5865
Department
Pediatrics