The rational development of CD5-targeting biepitopic CARs with fully human heavy-chain-only antigen recognition domains.
Zhenyu Dai, Wei Mu, Ya Zhao...
https://pubmed.ncbi.nlm.nih.gov/34274536Actively Recruiting
Phase 1
Age: 0 - 75Years
All Genders
ID03081910
Phase 1 Therapy Using Autologous and Donor-Derived T Cells Expressing a Second Generation CAR Targeting CD5 for T-Cell Malignancies
Led by Baylor College of Medicine · Updated on 2025-09-04
54
Participants Needed
2
Research Sites
639 weeks
Total Duration
On this page
Sponsors
B
Baylor College of Medicine
Lead Sponsor
C
Center for Cell and Gene Therapy, Baylor College of Medicine
Collaborating Sponsor
AI-Summary
What this Trial Is About
This research focuses on patients with a type of blood cancer called T-cell leukemia or lymphoma. It explores a new treatment combining two ways the body fights disease: antibodies and T cells. The study uses specially modified T cells that have an attached antibody called anti-CD5 and a stimulating protein called CD28, which may help these cells grow better and last longer to attack cancer cells. This is a Phase 1 trial investigating these modified T cells, called chimeric antigen receptor (CAR) T cells, in patients with T-cell malignancies expressing the CD5 antigen. The study collects T cells either from the patient or from a previous bone marrow transplant donor. These T cells are genetically modified in the lab using a virus to carry the antibody gene. Patients receive chemotherapy with cyclophosphamide and fludarabine before getting an intravenous infusion of the modified T cells at one of three dose levels. To reduce risk of a serious viral infection called Epstein Barr Virus (EBV), patients also receive Rituximab before the cell infusion. After infusion, patients are monitored closely for side effects and signs of infection. If patients respond well, they may receive up to three additional infusions and could proceed to a bone marrow transplant. Participants undergo various medical tests before, during, and after treatment, including physical exams, blood tests, and scans to measure tumor size. Blood samples are taken regularly for up to 15 years to track how long the modified T cells last and to monitor for viral infections. Patients stay near the treatment center for at least 6 weeks after infusion and visit the clinic frequently for monitoring. The primary outcome measured is the rate of dose-limiting toxicity within 6 weeks after infusion, and additional safety and response data are collected during the study and extension phases.
CONDITIONS
Brief Title
Autologous T-Cells Expressing a Second Generation CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen
Who Can Participate
Age: 0 - 75Years
All Genders
Eligibility Criteria
You may qualify if you...
- Diagnosis of recurrent T-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic lymphoma, or T-non-Hodgkin lymphoma
- Suitable for allogeneic hematopoietic stem cell transplant with an identified eligible donor
- CD5-positive tumor with more than 50% CD5 positive blasts confirmed by certified laboratory
- Age 18 to less than 75 years old
- Life expectancy greater than 12 weeks
- Availability of a partially-HLA matched allogeneic EBV-specific T cell line for treatment if needed
- Hemoglobin greater than or equal to 7.0 g/dL (transfusions allowed)
- Normal or acceptable kidney and liver function tests as specified
- Pulse oximetry greater than 90% on room air
- Karnofsky or Lansky score of 60% or higher
- Recovered from prior chemotherapy toxic effects at least one week before enrollment
- At least 60 days post-allogeneic hematopoietic stem cell transplant at treatment time
- Willingness to use effective birth control methods during and for 6 months after the study
- Informed consent provided and understood
You will not qualify if you...
- Active infection requiring antibiotics
- Active HIV infection
- History of other cancers except certain treated skin or in situ cancers within 2 years
- Receiving investigational agents or tumor vaccines within previous 6 weeks
- History of allergic reactions to murine protein products
- Pregnant or lactating women
- Tumor location risking airway obstruction
- Clinically significant viral infections or uncontrolled reactivation
- Acute graft versus host disease grade above II or active chronic GVHD above mild
- Current corticosteroid therapy for GVHD above specified dose
- Recent immunosuppressive treatment or donor lymphocyte infusion within 28 days
- Certain cardiac conditions including atrial fibrillation, recent heart attack, or poor heart function
- Central nervous system disorders or CNS-3 disease involving blast cells in spinal fluid
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
Standard medical tests including physical exam, blood tests, pregnancy test for females, and tumor measurements by scans and/or bone marrow studies.
Run-in Period
Duration - 3 days plus at least 1 day before infusion
Participants receive chemotherapy with cyclophosphamide and fludarabine to reduce their own T cells before receiving the CAR T cell infusion. A dose of Rituximab or similar drug is given after chemotherapy to reduce risk of viral complications.
3 daily doses of chemotherapy medications followed by 1 infusion of Rituximab before CAR T cell treatment.
Treatment
Duration - 1 day
Participants receive a single intravenous infusion of CD5.CD28 Chimeric Receptor T cells at the assigned dose. Before infusion, participants may receive Benadryl and Tylenol to prevent side effects.
1 infusion visit lasting 1 to 10 minutes, followed by observation in clinic for up to 3 hours.
Post-treatment Monitoring
Duration - At least 6 weeks, up to 8 weeks if evidence of viral reactivation
Participants remain locally for a minimum of 6 weeks after infusion for close monitoring of side effects and viral infections. During this period, participants visit the clinic at least twice a week for assessments and blood tests.
At least twice weekly visits for monitoring and blood tests during local stay.
Follow-up
Duration - Up to 15 years
Participants are followed for up to 15 years to monitor long-term safety and gene transfer side effects, including periodic blood tests and tumor assessments.
Scheduled blood draws and tumor measurements at multiple time points including 1 week, 2 weeks, 1 month, 3 months, 6 months, then every 6 months for 4 years and yearly thereafter.
Trial Site Locations
Total: 2 locations
1
Houston Methodist Hospital
Houston, Texas, United States, 77030
Actively Recruiting
2
Texas Children's Hospital
Houston, Texas, United States, 77030
Actively Recruiting
Loading map...
Research Team
R
Rayne Rouce, MD
M
Martha Arredondo
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
2
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here