Navigating Allogeneic Cell Therapy Clinical Trials

Allogeneic cell therapy clinical trials encompass a wide range of therapies, each with its own nuanced challenges. But collectively, allogeneic cell therapy clinical trials share several characteristics:

• The patients being treated are typically critically ill.
• The number of patients being treated is small, which requires many clinical trial sites to recruit a sufficient number of patients.
• The trials require long-term follow up with patients.
• The therapies have unique risks—like graft-versus-host disease (GVHD) and cytokine release syndrome—that are difficult to measure and require specialized clinical knowledge.

These characteristics make allogeneic cell therapy clinical trials complex and require substantial infrastructure support. This creates challenges for sponsors and clinical research organizations (CROs) working on the design, management, and oversight of cell therapy clinical trials. However, solutions exist to help clinical trials achieve success.

Design protocols that are easier to implement

Sponsors and CROs should involve the investigators at clinical trial sites along with patients as they design their clinical trial protocols. Often, the patients receiving an allogeneic cell therapy under a clinical trial are also candidates for receiving an allogeneic cell therapy or another therapy outside of the clinical trial. Therefore, designing protocols, data collection, and assessments around standard-of-care procedures makes the study easier for a center to implement and easier for patients to stay enrolled.

The site investigators can help sponsors and CROs understand the standard-of-care procedures and give feedback on the feasibility of what they are being asked to do. When possible, be flexible with clinical trial sites. Allowing a site to use its own procedures and technology can speed up the time to study activation at a center and improve center compliance.

Patients offer a unique perspective. They can review the protocol, consent forms, and advertising materials and give insights about how easy they are to follow and understand.

Sponsors and CROs should also closely examine the study requirements and only include study assessments that are absolutely necessary to evaluate study endpoints and safety. This reduces the burden of participation on sites and patients.

Ask about a CRO’s experience with the potential clinical trial sites

Academic medical centers typically have very specific research operations, and there is usually variation between centers. This is one of the major challenges of a large, multi-center clinical trial. It’s also why a CRO’s experience with the clinical trial sites a sponsor wants to target is so important.

When choosing a CRO, a sponsor should dig into the CRO’s experience with the sites as well as the CRO’s site selection process. Questions to ask a potential CRO include:

• How long have you worked with each center?
• What lessons have you learned in working with those centers?
• What factors into your site selection recommendations?
• How do you ensure a site’s recruitment strategy considers patient diversity?

Site selection should go beyond whether a center has the right number of patients. A CRO should have enough experience with a center to help the sponsor understand how the site has performed in similar clinical trials looking beyond enrollment to factors such as data quality.

A CRO should also be willing to work with a clinical trial site to fine tune their enrollment strategy and monitor enrollment to ensure sites are enrolling representative populations. A CRO’s experience with a center can offer insights into its ability to recruit diverse patients.

In addition, a CRO should set up a two-way path for communication once the clinical trial is underway and encourage investigators to provide honest feedback. This allows investigators to easily provide feedback on what they need to make the clinical trial work better. The sponsor and CRO can also help a site course correct if there are issues with the way a site is conducting the study.

Understand your CRO’s allogeneic cell therapy experience

Working with a CRO that has a solid foundation in the allogeneic cell therapy space can set sponsors up for success. A CRO with this expertise can be a true partner that can walk the sponsor through the nuances of allogeneic cell therapy clinical trial challenges.

That is especially true in data collection for cell therapy clinical trials. The clinical outcomes for which data needs to be collected are complex and, unlike other drugs, must be collected for many years after treatment. In addition, for an allogeneic product, the donor of the source material may also be considered a research subject along with the patient receiving the product. This adds to already complex clinical trial logistics as the CRO must understand how to collect data about the donor when the collection is occurring at a different institution, how to maintain confidentiality between the donor and recipient, and how to obtain informed consent from the donor, for example. That makes a CRO’s expertise and experience critical.

Monitoring patients for GVHD post-allogeneic cell therapy is a good example. GVHD data are challenging for sites to accurately report—and for CROs to monitor—because of the complexity in how GVHD presents clinically. A CRO with experience collecting these data will understand how to implement appropriate risk-based quality oversight processes because they know the common problems a site may encounter.

An experienced CRO can keep a close eye on the data, identify issues that matter as early as possible, and retrain and support a center to help the center submit higher quality data.

Create strong partnerships and ongoing collaboration

Sponsors and CROs face many challenges in the design, management, and oversight of allogeneic cell therapy clinical trials.

However, through ongoing collaboration and strong partnerships, sponsors and CROs can conduct successful clinical trials and advance allogeneic cell and gene therapy treatments for patients.

Kathleen Kane, MBA, CCRP, has worked in clinical research for 15 years. Throughout her career, she has held roles as a clinical research coordinator, regulatory specialist, project manager, monitor, and clinical operations manager. Kathleen is currently the senior manager of Clinical Operations in CIBMTR CRO Services at NMDP, a leader in cell therapy, helping find cures and saves lives for patients with blood cancers and disorders. Kathleen is also involved in the Association of Clinical Research Professionals (ACRP) and is the current president of the ACRP Upper Midwest Chapter.