Journal Article Clinical Trial, Phase II Ppublish
PubMed: 39374573 DOI: 10.1182/bloodadvances.2024014078
Incremental eligibility criteria for the BMT CTN 1507 haploidentical trial for children with sickle cell disease.
Blood Adv 8(23):6055-6063
Authors: Tami D John, Mark C Walters, Hemalatha G Rangarajan, Mahvish Q Rahim, Christopher McKinney, Catherine M Bollard, Ghada Abusin, Mary Eapen, Adetola A Kassim, Michael R DeBaun
Affiliations
- Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University, Palo Alto, CA.
- Hematology Division, Department of Pediatrics, University of California San Francisco, San Francisco, CA.
- Department of Pediatric Hematology, Oncology, Blood and Marrow Transplant, Nationwide Children's Hospital, Columbus, OH.
- Division of Hematology, Oncology, and Stem Cell Transplant, Riley Hospital for Children, Indianapolis, IN.
- Department of Hematology/Oncology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO.
- Department of Pediatrics, Center for Cancer and Immunotherapy Research, Children's National Hospital and The George Washington University, Washington D.C.
- Department of Pediatrics, C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor, MI.
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
- Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Meharry Sickle Cell Disease Center of Excellence, Vanderbilt University Medical Center, Nashville, TN.
- Department of Pediatrics, Division of Hematology/Oncology, Vanderbilt-Meharry Sickle Cell Disease Center of Excellence, Vanderbilt University Medical Center, Nashville, TN.
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 to 14.99 years with sickle cell disease (SCD) enrolling in a phase 2 trial of HLA-haploidentical hematopoietic stem cell transplantation. First, the enrollment was limited to overt stroke in the first 10 participants (stage 4). Subsequently, the DSMB reviewed the interim results and expanded the 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) and additions were made to the entry criteria that included nonneurologic morbidities (stage 2). Added eligibility criteria included the following: (1) life-threatening acute chest syndrome requiring exchange transfusion; (2) right heart catheterization confirmed pulmonary hypertension; (3) persistent systemic hypertension despite maximum medical therapy; (4) acute pain despite maximum medical therapy in the absence of psychosocial factors and unmanaged asthma after adjudication; and (5) 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. To our knowledge, for the first time, we introduce a staged strategy for eligibility in a curative therapy trial for children with SCD concordant with 45 Code of Federal Regulations § 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. This trial was registered at www.ClinicalTrials.gov as #NCT032635590.
MeSH
Cells, Hypertension, Microscopy, Electron, Scanning Transmission, Anemia, Sickle Cell, Aged, Therapeutics, Hematologic Diseases, Child