Comparing Outcomes for Young Adults with Severe SCD Treated with HLA-Identical Sibling and Matched Unrelated HCT versus Standard Supportive Care

Hematopoietic Stem Cell Transplantation for Young Adults with Sickle Cell Disease (STRIDE-2)

BMT CTN 1503, ClinicalTrials.Gov identifier pending

National Heart, Lung, and Blood Institute, National Institutes of Health

Emory University

Multiple clinical centers throughout the United States

180-200 patients (60 for the transplantation arm and 120-140 for the parallel comparison cohort)

STRIDE-2 will open as a multicenter trial designed to compare clinical outcomes for young adults with severe sickle cell disease (SCD) after hematopoietic cell transplantation (HCT). For a variety of reasons, a randomized clinical trial for HCT or observation is not practical. Thus, eligibility will be determined on the biological assignment of HLA-identical siblings or well-matched unrelated donors,¹  with those lacking an eligible donor for HCT serving as a comparison group. The eligibility criteria for STRIDE-2 include age 15 to 40 years and severe SCD. Indications for HCT in SCD were previously described.²  The conditioning regimen will include busulfan, fludarabine, and rabbit antithymocyte globulin, and graft-versus-host-disease (GvHD) prophylaxis will include cyclosporine or tacrolimus in addition to post-transplant methotrexate. The primary outcome measure will assess overall and event-free survival (EFS) at two years from the biological assignment between the two transplant arms and the standard care arm. Comparing outcomes of the transplant cohort with standard supportive care in young adults with severe SCD provides the ability to assess the impact of HCT on attenuating end-organ function in this high-risk population.

Currently, HCT is the only curative option for SCD and recently became available for the increasing population of young adults with severe SCD. Nonmyeloablative regimens have been successful, with high engraftment rates of 87 percent and low mortality rates of 3 percent in a single-center trial.³  The pilot study, STRIDE (NCT01565616), assessed the feasibility and safety of these donor sources using a nonmyeloablative conditioning regimen in 15 young adults with severe SCD (results pending). STRIDE-2 is the first trial dedicated to comparing outcomes for young adults with severe SCD treated with HCT versus standard supportive care. This study has the potential to establish guidelines on when to recommend HCT and may broaden the therapeutic techniques for young adults with severe SCD.

The STRIDE-2 trial represents the next level of research for HCT in severe SCD using HLA-identical siblings and unrelated donors for HCT compared with standard care due to the absence of a suitable donor. A potential challenge for STRIDE-2 includes identifying HLA-identical donors for the transplantation arm. Previous HCT trials in adults with SCD demonstrated that only 14 to 17 percent of those screened have an HLA-matched sibling donor,^4,3  and those with matched unrelated donors range from 19 to 27 percent.^5,6  With a multicenter approach, however, STRIDE-2 should increase awareness of HCT in SCD and accelerate enrollment.