Trial to assess CAR T-cell therapy for certain lymphomas, leukemias

Researchers are launching a first-in-human clinical trial to assess the use of chimeric antigen receptor T-cell therapy targeting the CD4 protein among patients with relapsed and refractory T-cell lymphoma and leukemia.

Huda S. Salman, MD, oncologist at Stony Brook University Cancer Center, and colleagues at University of Louisville and iCell Gene Therapeutics received FDA investigational new drug clearance for the novel therapy.

Patient accrual for the phase 1 clinical trial is underway.

“We are excited to partner with the University of Louisville and iCell Gene Therapeutics to offer this innovative first-in-human chimeric antigen receptor (CAR) T-cell immunotherapy clinical trial for patients who are suffering from these extremely difficult-to-treat T-cell lymphomas and leukemias,” Salman said in a press release. “CD4 CAR T cells may prove to be a promising and novel therapy in this setting.”

HemOnc Today spoke with Salman about the trial, the need for more effective treatment options for this patient population, the rationale for this particular therapeutic approach, and the potential implications if it is proven effective and safe.

Question: Can you describe the need for new and effective treatments for this patient population?

Answer: There is a significant unmet need. In the past, most clinical trials that included patients with T-cell lymphoma also included B-cell lymphomas. Outcomes for these patients have remained poor due to the lack of specificity of current available therapy. This novel therapy should be more specific and designed to target this specific population of patients.

Q: What is the rationale for this treatment approach targeting the CD4 protein?

A: These tumors almost invariably express CD4 protein on their cell surface. In the past, CD4 protein was targeted with less effective therapy. Monoclonal antibodies helped identify CD4 as a target.

Q: How does this target vary from the targets of most other CAR T-cell therapies?

A: Targets are cancer-specific and different CAR T cells have specific targets. The most popular and established therapies available now target CD19 and CD20 on B-cell lymphomas. However, many clinical trials are designed to target other cellular antigens expressed by other tumors, one of which is CD4 on T-cell malignancies.

Q: How will the trial be conducted?

A: This is a phase 1 clinical trial designed to identify the appropriate dose of the therapy, as well as to describe what toxicities might be associated with it and the observed efficacy among this patient population. The targets are T-cell malignancies that have CD4 protein expressed, including T-cell lymphomas and T-cell leukemias. We are planning to treat between 15 and 20 patients on this trial, but this all depends on how the dose-escalation goes. In addition to having CD4 expression, patients should have enough T cells to manufacture CAR and should demonstrate adequate response to cytoreductive chemotherapy that is given before we administer the CAR T-cell therapy. The CD4 CAR T cell is manufactured from the patient’s own cells. Once these cells are infused back into a patient through an IV, they multiply and attack tumor cells efficiently throughout the body. Patients will be treated in the hospital and will be closely followed-up after hospital discharge.

Q: What is the timeline ?

A: We expect the trial to complete enrollment in 18 months. Results will be reported in the interim and after trial completion.

Q: What are the potential implications if this approach is proven safe and effective?

A: The implications are potentially broad. These patients lack effective therapies. We treat with intention to cure and/or to bridge them to another curative therapy, such as bone marrow or stem cell transplantation. Giving patients this hope will be very rewarding for them, but also for us clinicians.

Q: If this trial is successful, what is the next step ?

A: The next phase will be an efficacy trial that enrolls more patients. Once we can show that the therapy is effective and safe, we will then seek FDA approval. – by Jennifer Southall

For more information:

Huda S. Salman, MD, can be reached at Stony Brook University Cancer Center, 3 Edmund D. Pellegrino Road, Stony Brook, NY 11794; email: huda.salman@stonybrookmedicine.edu.

Disclosure: Salman reports no relevant financial disclosures.