Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma.
Moritz Ernst, Annika Oeser, Burcu Besiroglu...
https://pubmed.ncbi.nlm.nih.gov/34515338Actively Recruiting
Phase 1
Age: 18Years +
All Genders
ID04545762
Phase 1 Trial of Anti-CD19 CAR-T Cells for Relapsed or Refractory Non-Hodgkin Lymphoma
Led by C. Babis Andreadis · Updated on 2026-01-14
36
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
C
C. Babis Andreadis
Lead Sponsor
U
University of California, Davis
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and feasibility of infusing genetically modified autologous T cells that express a chimeric antigen receptor targeting the CD19 antigen found on B cells. This open-label phase 1 study focuses on participants with relapsed or refractory CD19-positive B-cell non-Hodgkin lymphoma (NHL), including specific cohorts with Burkitt lymphoma and marginal zone lymphoma or Waldenström macroglobulinemia. The goal is to assess the safety profile, determine the recommended dose for future studies, and explore the manufacturing feasibility of this cellular therapy. Participants will undergo apheresis to collect their own lymphocytes, followed by a manufacturing process lasting approximately 13 to 14 days to produce the anti-CD19 CAR-T cells. Before infusion, they receive a lymphodepleting chemotherapy regimen consisting of intravenous cyclophosphamide and fludarabine. The CAR-T cells are then infused over 5 to 30 minutes. The dose escalation phase is closed to enrollment, while the dose expansion phase treats specific lymphoma subtypes with the maximum tolerated dose established earlier. During the study, participants are monitored closely for safety and response. Follow-up includes assessments up to 12 months after infusion to evaluate adverse events and treatment effects, with long-term survival follow-up extending up to 15 years. Researchers will measure the proportion of participants experiencing treatment-emergent adverse events, dose-limiting toxicities, and response rates, as well as the ability to manufacture the CAR-T cells. The study involves detailed clinical evaluations and laboratory testing to monitor health and disease status throughout the participation period.
CONDITIONS
Brief Title
Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Diagnosis of relapsed or refractory Burkitt Lymphoma with prior exposure to anti-CD20 antibody and anthracycline
- No significant circulating malignant cells causing elevated lymphocyte count
- Measurable PET-positive disease for Burkitt Lymphoma
- Diagnosis of relapsed or refractory Marginal Zone Lymphoma or Waldenström Macroglobulinemia with at least 2 prior chemoimmunotherapy lines including anti-CD20 antibody and alkylating agent
- Measurable PET-positive disease or serum monoclonal IgM paraprotein > 0.5 g/dL for Marginal Zone or Waldenström Macroglobulinemia
- Symptomatic disease requiring systemic treatment for indolent lymphomas
- CD19-positive confirmed by biopsy or flow cytometry
- Age 18 years or older at consent
- Absolute lymphocyte count > 100/µL
- ECOG performance status less than 2
- Adequate organ function including bone marrow, hemoglobin >8 g/dL, platelets >50,000/µL, ANC >500/µL, liver enzymes and bilirubin within limits, serum creatinine <2x ULN
- Adequate cardiac function with LVEF >40%
- Adequate vascular access for leukapheresis
- Negative pregnancy test and agreement to use contraception for women of childbearing potential
- Agreement to contraception for males with partners of childbearing potential
- Ability to understand and sign informed consent
You will not qualify if you...
- Autologous transplant within 6 weeks before planned CAR-T infusion
- Prior CD19-targeted CAR-T cell therapy outside this protocol
- Active malignancy other than non-melanoma skin cancer or carcinoma in situ
- HIV seropositivity
- Active hepatitis B or C infection confirmed by PCR positive
- Uncontrolled illnesses including active infections, symptomatic heart failure, unstable angina, arrhythmia, pulmonary abnormalities, or psychiatric/social limitations
- Pregnant or breastfeeding women
- History of significant CNS disorders such as epilepsy, seizure disorders, paresis, aphasia, cerebrovascular disease, severe brain injury, dementia, or Parkinson's disease
- Autoimmune disease requiring immunosuppressive medication within 6 months
- Body weight less than 40 kilograms
- Laboratory abnormalities considered clinically significant
- Use of corticosteroids within 7 days prior to infusion except for anti-emesis during chemotherapy
- New neurologic symptoms or uncontrolled CNS lymphoma involvement
- ECOG performance status 2 or higher
- Evidence of uncontrolled intercurrent illness
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Approximately 18 days
Participants undergo apheresis to collect lymphocytes followed by approximately 13 to 14 days of CAR-T cell manufacturing. During this time, they receive chemotherapy with cyclophosphamide and fludarabine before a single infusion of anti-CD19 CAR-T cells. Participants are monitored closely during this treatment period.
1 apheresis visit, multiple chemotherapy visits, and 1 infusion visit
Follow-up
Duration - 12 months for active follow-up; up to 15 years for long-term follow-up
Participants are followed for up to 12 months after CAR-T cell infusion to monitor safety, efficacy, and remission status. Long-term survival follow-up continues up to 15 years.
Regular follow-up visits for 12 months, then annual visits for up to 15 years
Trial Site Locations
Total: 1 location
1
University of California, San Francisco
San Francisco, California, United States, 94143
Actively Recruiting
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Research Team
U
UCSF HDFCCC Cancer Immunotherapy Program
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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