Designing High-Impact Clinical Trials That Serve Patients, Clinical Centers, and Industry Sponsors

Clinical Researcher—June 2023 (Volume 37, Issue 3)


Erin Leckrone, MFA, MBA


Clinical trials are critical in developing effective and safe new treatments and improving patient outcomes. When well-designed and managed, they benefit participants, investigators, trial sponsors, and the entire medical community. They are vital to the advancement of the science of cellular therapy, including hematopoietic cell transplantation (HCT). Approximately 25,000 treatments and outcomes involving HCT or cellular therapy for cancer and other life-threatening disorders are reported to the CIBMTR® (Center for International Blood and Marrow Transplant Research®) annually, a number that increases by about 5% per year.{1} However, trials in the HCT space have complex challenges that impact the clinical trial sponsors, investigators, clinical trial sites, physicians, patients, and their caregivers, ranging from trial design to patient or donor selection to long-term follow up.

Expanding Access

When patients understand all their treatment options—including clinical trials—they can make informed decisions. However, it can be difficult for patients to find and join clinical trials and, all too often, ethnically diverse populations are underrepresented. Widespread participation in clinical trials across populations is essential to ensure scientific innovations are safe and effective for all patients who may need therapy.

A recent analysis by the Blood and Marrow Transplant Clinical Trials Network, which focuses on clinical trials for HCT and cellular therapy, demonstrates the widespread challenge of ensuring ethnically diverse patient enrollment in clinical trials. The organization analyzed and compared the race and ethnicity of the patients enrolled in nine clinical trials spanning 2014 to 2021 to the race and ethnicity of the total United States population using 2020 census data, all potentially eligible HCT recipients at participating trial centers at the time of trial enrollment, and all potentially eligible HCT recipients at all transplant centers in the United States at the time of trial enrollment.

In all but one trial, the proportion of underrepresented racial and ethnic group participants was lower than the general population. In six of the nine trials, the proportion of participants from such groups was lower than those potentially eligible at the participating centers.{2} This analysis contained valuable lessons on improving clinical trial participation.{3}

There are a number of organizations that provide resources for patients, clinical sites, and industry sponsors. The National Marrow Donor Program/Be The Match’s Clinical Trials Search and Support Program includes a searchable clinical trial database, one-on-one support, financial grants, and patient resources in plain language.

In addition, clinical research organizations (CROs) can take steps to broaden access to trials, including:

  1. Prioritizing and routinely monitoring diversity in the clinical trial accrual plan.
  2. Broadening eligibility criteria even further.
  3. Collaborating with advocacy organizations and community groups.
  4. Helping patients understand clinical trials.
  5. Making it easy for patients to comply with follow-up assessments.
  6. Using diversity resources to identify opportunities for improvement.

Finally, ongoing research can help address this gap, specifically when it comes to eligibility. For example, many allogeneic HCT clinical trials require a patient to have a fully matched (8/8) donor to enroll. The chance of having a matched, available unrelated donor on the Be The Match Registry® varies significantly depending on a patient’s ancestral background, and currently ranges from 29% for Black and African American patients to 79% for non-Hispanic white patients.{4}

A recent clinical trial demonstrates what can happen when eligibility criteria expand beyond fully matched donors. Known as the 15-mismatched unrelated donor (15-MMUD) trial (NCT02793544), it assessed the safety and efficacy of using bone marrow from MMUDs in combination with PTCy graft-versus-host disease (GVHD) prophylaxis. The researchers concluded this approach was safe and effective and could significantly expand HCT access, especially for those who are ethnically diverse. In addition, the researchers noted 48% of patients enrolled in 15-MMUD were ethnically diverse, which is almost double the typical enrollment in HCT clinical trials.{5}

CROs and sites must work together to improve diversity in clinical trial enrollment in all areas of medicine to advance health equity for racially and ethnically diverse patients.

Collaborative Expertise

A collaborative approach to cell therapy clinical trial challenges pushes the boundaries of discovery and speeds life-saving treatments to patients. When organizations collaborate, sponsors can leverage unique expertise, unparalleled resources, and an established, stable infrastructure, including research, sites, donors, partnerships, and scientific and operational expertise. As a result, the time required to design, launch, and execute high-impact clinical trials is significantly reduced.

This collaboration can span the clinical trials continuum that starts with clinical trial design and management focused on the patient experience and ends with outcomes collection, research, and long-term follow-up. It also includes search and support services that help patients understand, find, and enroll in clinical trials. This type of collaborative nature helps ensure the successful execution of internally sponsored, industry, and academic studies and gives many patients access to life-saving treatments. One example of this type of collaboration among industry, academia, and CROs relates to the approval process for abatacept.

In December 2021, the U.S. Food and Drug Administration (FDA) approved abatacept for the prevention of acute graft-versus-host disease (aGVHD) for patients aged 2 and older who received a matched or mismatched unrelated donor (MMUD) transplant. It is the first FDA-approved drug for the prevention of aGVHD and will increase access to HCT for more patients with hematologic malignancies and disorders.

The FDA based its approval on the safety and efficacy data from two separate studies: the Phase II clinical trial GVHD-1 (also known as ABA2){6} and a confirmatory observational study, GVHD-2.{7} Our CIBMTR CRO Services prospectively supported the GVHD-multicenter ABA2 study that included a double-blind, placebo-controlled cohort and an open-label, single-arm cohort. The GVHD-2 study used real-world data provided by CIBMTR to further evaluate the impact of abatacept on the survival of HCT recipients with a 7/8 MMUD.

The CIBMTR CRO Services is supporting the currently enrolling ABA-3 trial (NCT04380740). This multicenter, randomized, double-blind, Phase II trial is investigating extended dosing of abatacept in MMUD recipients with a goal to reduce the risk of chronic GVHD.

Challenges and Complexities on the Road to Innovation

Clinical trials are critical to improve outcomes for patients and advance the science of life-saving cell therapies. With the unique challenges and complexities of these innovative treatments, academic and industry sponsors can benefit from the synergies offered by industry organizations and nonprofits that include:

  • End-to-end clinical trial design, operations, and logistics support.
  • Built-out clinical infrastructure with a single institutional review board, dedicated data and safety monitoring board, master contracts, and technology that is compliant with the expectations of 21 CFR Part 11 in the Code of Federal Regulations.
  • Access to patients and allogeneic donors for research.
  • Models, analyses, and interpretations to help sponsors define their targets.
  • Direct link to the CIBMTR Research Database with information on more than 630,000 patients.
  • Industry-leading infrastructure to collect and analyze patient outcomes data.


With careful planning, execution, and patient support, cell therapy clinical trials will pave the way for new treatments for all patients and may serve as a model for best practices in other areas of medicine.


  1. Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Annual Report, May 2021 – April 2022.
  2. Horowitz MM, Kaur M, Mendizabal A, et al. 2022,Racial and ethnic diversity on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials — We can do betterTransplant Cell Therapy 28(3):S71. doi:10.1016/s2666-6367(22)00244-5
  3. DeSalvo A, Horowitz MM, Lee C. Diversifying Enrollment in Clinical Trials: Where We Are, Where We Need to Be and How to Get There. The ONE Forum 2022.
  4. Auletta J. 2022. Mismatched Unrelated Donors Expand Transplant Access to Diverse Populations.Hematology Advisor.
  5. Shaw BE, Jimenez-Jimenez AM, Burns LJ, et al. 2021. National Marrow Donor Program–Sponsored Multicenter, Phase II Trial of HLA-Mismatched Unrelated Donor Bone Marrow Transplantation Using Post-Transplant Cyclophosphamide. Journal of Clinical Oncology 39(18):1971–82. doi:10.1200/JCO.20.03502
  6. Bristol Myer Squibb. 2021. U.S. Food and Drug Administration Approves Orencia® (abatacept) in Combination with a Calcineurin Inhibitor and Methotrexate for the Prevention of Acute Graft Versus Host Disease (aGvHD).

Erin Leckrone, MFA, MBA,
is Senior Director of Clinical Trials at the CIBMTR® (Center for International Blood and Marrow Transplant Research).