Clinical trials are fundamental to the continuing advancement of life-saving cell therapies, including hematopoietic cell transplantation (HCT). On Clinical Trials Day, the NMDP℠ wants to recognize those involved in trials, help raise awareness of clinical trials—and of clinical research—and ensure that researchers, physicians and patients know about the extensive resources available to support the development of new cellular therapies through the CIBMTR® Clinical Research Organization (CRO) Services.
These CRO Services are a collaborative effort between NMDP BioTherapies℠ and the CIBMTR, resulting in unique expertise and access to unparalleled resources, including research, sites, donors, partnerships, and scientific and operational expertise.
Early clinical trials
In 1747, James Lind, a pioneer of naval hygiene, conducted what is considered the first randomized clinical trial. According to the Association of Clinical Research Professionals (ACRP), Lind had the idea that scurvy was caused by decay of the body that could be cured through the introduction of acids.
He recruited 12 men who it is written were provided informed consent and six different daily treatments for 14 days, to two men each. The test showed that those allocated citrus fruits had the best results. While primitive compared to today’s standards, his design and comparison of like with like may have inspired and informed future clinical trial design.
Even though clinical trials have advanced exponentially, cell therapy clinical trials still present unique challenges and complexity—from design to patient or donor selection to long-term follow-up. These impact the clinical trial sponsor, investigators, clinical trial sites, physicians, and patients and their caregivers.
Unparalleled collaborative expertise overcomes design challenges
NMDP and NMDP BioTherapies applied more than 35 years of experience to develop capabilities that mitigate cell therapy clinical trial challenges while specializing in the design, implementation and oversight of cellular therapy clinical trials. The organization has sponsored its own trials and led successful trials in the academic and cell and gene therapy industry space, ultimately expanding patient access to trials.
NMDP BioTherapies and the CIBMTR CRO allow sponsors to leverage unique expertise and access 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 support spans the clinical trials continuum that starts with CIBMTR CRO Services for clinical trial design and management with an eye for the patient experience and ends with outcomes collection, research and long-term follow-up. It also includes the NMDP Jason Carter Clinical Trials Search and Support Program, which helps patients understand, find and enroll in clinical trials.
Our collaborative nature has ensured the successful execution of internally sponsored and industry and academic studies and given many patients access to life-saving treatments.
CIBMTR facilitates critical observational and interventional research through scientific and statistical expertise, an extensive network of centers, and a unique database of long-term clinical data for more than 630,000 patients who have received HCT and other cellular therapies.
Its 70+ person CIBMTR CRO Services team focuses only on cell therapy and HCT clinical trial design and oversight, emphasizing collaboration with organizations for the highest patient-impact clinical trials. The organization’s cell therapy and HCT experts provide clinical insights that optimize protocol design and lay a foundation for successful clinical trials.
Established relationships and contracts with investigational sites, donor centers and research lab partners throughout the United States allow NMDP to:
- Recruit high-impact sites to participate in trials
- Complete site start-up faster
- Expedite operational processes throughout the study
CIBMTR CRO capabilities ensure successful trials
CIBMTR CRO Services supports clinical trials of all phases, with specific expertise in Phase I and Phase II trials.
With its dedicated staff and a large network of investigational sites and partners, CRO Services provides complete clinical trial services that can be used as a whole or as needed for each trial. These include:
- Protocol development and approvals
- Project management
- Site selection, start-up and management
- Study monitoring
- Lab and research sample oversight
- Patient-reported outcomes collection
- Database build and data management
- Statistics and data analysis
- Medical and safety monitoring
- Contracts and financial administration
- Institutional Review Board (IRB) and Data Safety Monitoring Board (DSMB)
Beyond the trial—solving donor and patient selection challenges
NMDP BioTherapies helps advance the development of new cell therapies by providing customizable services for the end-to-end cell therapy supply chain. Backed by the industry-leading experience of NMDP and a research partnership with the CIBMTR, the organization designs solutions that empower the discovery, development and delivery of next-generation cellular therapies across the globe.
- Donors: The NMDP Registry℠ is the most diverse registry of potential unrelated donors and cord blood units worldwide. In the last 35 years, the organization facilitated more than 120,000 cell therapies, mostly time-sensitive allogeneic transplants. The work on these therapies drove the development of sophisticated search and match and logistics capabilities which identify donors that match the specific characteristics an investigator needs and deliver the cells where and when they are needed.
- Defining targets: Bioinformatics Consulting Services helps mitigate risk by using data-driven answers to help investigators make informed decisions that maximize clinical trial success. NMDP applies software tools and analytical methods to facilitate data exchange, interpret information, understand patterns, and predict factors to help sponsors define their targets and build their off-the-shelf cell banks.
Long-term follow-up: observational studies
Most cell and gene therapies are designed to achieve permanent or long-lasting effects in the human body, which inherently increases the risk of delayed adverse events. To completely understand and mitigate the risk of delayed adverse events, participants in gene therapy trials need to be monitored for an extended period of time. This is commonly referred to as the long-term follow-up (LTFU) period of a clinical study. Collecting and assessing data from a multitude of trials will provide the most comprehensive insights possible. In fact, the FDA requires pharmaceutical companies that commercialize genetically engineered cell therapies to follow therapy recipients for up to 15 years to evaluate safety and efficacy. This can be a daunting undertaking.
CIBMTR established protocols to address this need. It collaborates with centers globally to collect clinical outcomes information for therapies performed worldwide, including allogeneic transplants, autologous transplants, and other cellular therapies. Their data includes outcomes statistics for virtually all allogeneic transplants and about 80% of the autologous transplants performed in the U.S. This data aids in clinical decision-making, protocol development or other information-specific needs.
Their wide-ranging studies examine questions that are difficult or impossible to address in single-center studies or randomized trials because the diseases studied are uncommon, single centers treat few patients with a given disorder, and not all important questions are amendable to a randomized research design. CIBMTR also supports investigators in conducting cellular therapy observational studies.
Conclusion
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 NMDP and NMDP BioTherapies offer with CIBMTR, including:
- End-to-end clinical trial design, operations and logistics support
- Built-out clinical infrastructure with a single IRB, dedicated DSMB, master contracts and 21 CFR part 11 compliant technology
- 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
During an FDA Office of Tissues and Advanced Therapies (OTAT) Town Hall on Sept. 29, 2022, the FDA said that GMP does not apply to the collection of allogeneic starting material. Specifically, an FDA official said companies only need to adhere to 21 CFR 1271 subpart C and do not need to collect allogeneic starting material under full GMP conditions. The requirement for adherence to GMPs starts at the manufacturing sites.
With careful planning, execution and patient support, cell therapy clinical trials will pave the way for new treatments for patients. Contact us for more information. We’re ready to discuss how we can help.
