First Patient Treated in New Study Investigating Graft-Versus-Host-Disease (GVHD) Prevention Strategies for Mismatched Unrelated Donor Hematopoietic Cell Transplants

August 06, 2025 at 09:00 AM EDT

ACCELERATE is the first randomized clinical trial to study GVHD prevention in the mismatched unrelated donor (MMUD) setting and uses a unique platform design to compare novel GVHD strategies to a standard of care control arm, aiming to reduce GVHD, improve survival and minimize side effects for patients

NMDP^SM, a global nonprofit leader in cell therapy, and its collaborative research program, CIBMTR® (Center for International Blood and Marrow Transplant Research®), announced today that the first patient began treatment as part of the groundbreaking ACCELERATE clinical trial, which compares novel GVHD prevention strategies against the current, standard of care regimen of post-transplant cyclophosphamide (PTCy) for patients undergoing mismatched unrelated donor (MMUD) peripheral blood stem cell (PBSC) transplants. The patient was enrolled at The University of Texas MD Anderson Cancer Center.

“This trial is a major milestone in our efforts to reduce GVHD for patients who don’t have a fully matched donor as well as advance treatment options and outcomes,” said Steven Devine, MD, chief medical officer, NMDP, and senior scientific director, CIBMTR. “What sets ACCELERATE apart is its adaptive design, which allows us to test multiple, investigational study arms simultaneously, modifying, improving and learning from the approach as we go.”

In this randomized, unblinded, Phase 2, multi-center platform trial, participants will be randomly assigned to either the control or investigational study arm and monitored for up to one year after transplant. All participants will receive MMUD PBSC transplant and PTCy-based GVHD prophylaxis using a standard-dose (control arm) or a reduced-dose of PTCy in combination with either abatacept or ruxolitinib (investigational arms). Both the control and investigational arms will combine respective dosing for PTCy with mycophenolate mofetil (MMF) and tacrolimus to see which works best at preventing GVHD while minimizing side effects. The primary endpoint is GVHD-free, relapse-free survival (GRFS) at one year. Secondary endpoints include overall survival, disease-free survival, acute and chronic GVHD, relapse, infection and patient-reported quality of life.

Conventionally designed clinical trials often take years to produce analyses and results. By contrast, a platform protocol design expedites knowledge for researchers—ultimately benefiting patients—because its design is agile, allowing new regimens to be added or retired based on the emerging data it produces. Each new regimen is tested in two steps: first in a small group to ensure it is safe (safety run-in phase), and then in a larger group to compare its effectiveness in comparison to the standard of care.

ACCELERATE is expected to enroll 358 patients at up to 60 investigational centers across the U.S. Final data collection for primary outcomes is projected to conclude in 2028, with full study completion of the initial investigational arms possible by 2029.

“Not only is ACCELERATE groundbreaking in its approach, this trial is also the culmination of a decade of transformational advances and the reimagining of transplant care, benefiting patients of all backgrounds—especially those who have historically lacked access to clinical trials,” said Jeffery Auletta, MD, senior vice president, CIBMTR & Clinical Services, NMDP, and Chief Scientific Director, CIBMTR NMDP. “With our network of transplant centers, we are watching the rising tide of clinical MMUD adoption, embarking on the next wave of advances, together.”

In the decade since NMDP and CIBMTR’s first trial launched, later demonstrating the feasibility of the novel MMUD-PTCy method to prevent GVHD, clinical adoption rates have steadily increased, with over 80% of MMUD transplants in adult patients using this approach in 2023.¹

Historically, finding an available matched unrelated donor (MUD) on international registries has been limited for patients with ethnically diverse ancestry—from as low as 29% for Black or African American patients and 48% for Latino and Hispanic patients versus 79% for non-Hispanic white patients. Research led by NMDP and CIBMTR has demonstrated that MMUD HCT using PTCy-based GVHD approaches result in outcomes equivalent to fully matched donors expanding match rates to nearly 100% for all patients regardless of ancestry.²

NMDP-led Donor for All research

ACCELERATE is one in a series of NMDP-sponsored, CIBMTR-conducted clinical trials designed to improve all patient outcomes by studying the use of PTCy-based GVHD prophylaxis in MMUD HCT (patients matched at 4/8 to 7/8 alleles considering HLA-A, -B, -C and -DRB1). ACCELERATE builds on the positive results from previous trials, including:

The groundbreaking 15-MMUD trial (NCT02793544) showed PTCy was effective in decreasing risk for GVHD in adults with hematologic malignancies receiving MMUD bone marrow transplants.
The ACCESS trial (NCT04904588) established safety and efficacy using PTCy-based GVHD prophylaxis following MMUD PBSC transplants, significantly expanding access to curative therapy for patients with blood cancers. Full results from the adult cohort are anticipated later this year.
The OPTIMIZE clinical trial (NCT06001385), is evaluating whether a reduced dose of PTCy would safely and effectively prevent GVHD while reducing infection risk in patients with hematologic malignancies receiving PBSC HCT from MMUDs. Enrollment is nearly complete.

About CIBMTR®

CIBMTR® (Center for International Blood and Marrow Transplant Research®) is a nonprofit research collaboration between NMDP^SM, in Minneapolis, and the Medical College of Wisconsin (MCW), in Milwaukee. CIBMTR collaborates with the global scientific community to increase survival and enrich quality of life for patients. CIBMTR facilitates critical observational and interventional research through scientific and statistical expertise, a large network of centers, and a unique database of long-term clinical data for more than 680,000 people who have received hematopoietic cell transplantation and other cellular therapies. It is funded by the National Cancer Institute, the National Heart, Lung and Blood Institute and the National Institute for Allergy and Infectious Disease, the Health Resources and Services Administration, the Office of Naval Research, industry sponsors, MCW, and NMDP. Learn more at cibmtr.org.

About NMDP^SM

At NMDP^SM, we believe each of us holds the key to curing blood cancers and disorders. As a global nonprofit leader in cell therapy, NMDP creates essential connections between researchers and supporters to inspire action and accelerate innovation to find life-saving cures. With the help of blood stem cell donors from the world’s most diverse registry and our extensive network of transplant partners, physicians and caregivers, we’re expanding access to treatment so that every patient can receive their life-saving cell therapy. NMDP. Find cures. Save lives. Learn more at nmdp.org.

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¹ Spellman SR, Xu K, Oloyede T, et al. Current activity trends and outcomes in hematopoietic cell transplantation and cellular therapy - A report from the CIBMTR. Transplant Cell Ther. 2025:S2666-6367(25)01198-4. doi: 10.1016/j.jtct.2025.05.014. Online ahead of print.

² Chowdhury AS, Maiers M, Spellman SR, Deshpande T, Bolon YT, Devine SM. Existence of HLA-mismatched unrelated donors closes the gap in donor availability regardless of recipient ancestry. Transplant Cell Ther. 2023;29(11):686.e1-686.e8. doi: 10.1016/j.jtct.2023.08.014. Epub 2023 Aug 14.