Actively Recruiting
Fludarabine and Cyclophosphamide With or Without Rituximab Before CD19 Chimeric Antigen Receptor T Cells for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Led by Mehrdad Abedi, MD · Updated on 2024-05-13
36
Participants Needed
1
Research Sites
221 weeks
Total Duration
On this page
Sponsors
M
Mehrdad Abedi, MD
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
This phase I trial evaluates the best dose, possible benefits and/or side effects of fludarabine and cyclophosphamide with or without rituximab before CD19 chimeric antigen receptor T cells in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or has not responded to previous treatment (refractory). T-cells are a normal part of the immune system. To make the T-cell medication, T-cells are taken from the blood and altered in a laboratory. They are then returned to the body. The altered T-cells will latch on to a specific part of the cancer cells and hopefully kill them. Once the T-cells have been altered in the laboratory, they are called "CAR T-cells." CAR is short for "chimeric antigen receptors." These are structures on the surface of cells that allow the altered T-Cells to find and destroy the cancer cells. Another part of the T-Cell medication is called "CD19." This part is called a "biomarker." Biomarkers help doctors determine whether a cancer is getting worse and whether medications are working to stop it. The chemotherapy drugs that are given before the T-Cell therapy are cyclophosphamide, fludarabine and rituximab. Rituximab is an immunotherapy drug. These chemotherapy drugs will reduce the number of normal (unaltered) T-Cells in the body to make room for the altered T-cells to kill the cancer cells. Giving fludarabine and cyclophosphamide with or without rituximab before CD19 CAR T cell therapy may help improve response to CD19 CAR T cell therapy in patients with diffuse large B-cell lymphoma.
CONDITIONS
Official Title
Fludarabine and Cyclophosphamide With or Without Rituximab Before CD19 Chimeric Antigen Receptor T Cells for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Signed informed consent form provided
- Willingness to follow all study procedures and be available for the full study duration
- No commercial CD19 CAR T cell product available
- Male or female aged 18 years or older
- In good general health as deemed by the investigator
- Able to swallow oral medication and willing to follow study treatments
- Females of childbearing potential must use effective contraception and have a negative pregnancy test
- Males of reproductive potential must use condoms or effective contraception
- Agree to avoid tobacco and drug use during the study
- Diagnosis of relapsed or refractory diffuse large B cell lymphoma after at least two prior therapies
- Disease must be CD19 positive by biopsy
- Eastern Cooperative Oncology Group (ECOG) performance status of 1 or better for adults
- Absolute neutrophil count (ANC) of at least 1000 (or 500 with bone marrow involvement)
- Platelet count of 100,000/mm3 or higher
- Hemoglobin greater than 8 g/dL
- Kidney function with creatinine clearance of 50 cc/min or more
- Total bilirubin 2 mg/dL or less (up to 3 mg/dL if Gilbert's Syndrome)
- Liver enzymes (ALT and AST) within 3 times the upper limit of normal (or 5 times if liver involved)
- Cardiac ejection fraction 45% or greater with no significant ECG abnormalities
- Oxygen saturation over 92% on room air
- At least 2 weeks since prior systemic therapy
- No use of lymphodepleting agents for 7 days before blood collection and for 90 days after CAR T cell infusion
You will not qualify if you...
- Use of supplemental oxygen or presence of cardiac pacemaker
- Known allergy to components of the anti-CD19 CAR T cell product
- Fever within 3 days before starting lymphodepleting chemotherapy
- Treatment with other investigational drugs within 2 weeks before blood collection
- Primary immunodeficiency
- Autoimmune diseases causing organ damage or requiring immunosuppressive drugs within 2 years
- Recent autologous transplant within 6 weeks or allogeneic transplant within 3 months
- Prior CD19 CAR T cell therapy outside this study
- Active central nervous system or meningeal tumor involvement
- Untreated brain metastases or central nervous system disease
- History of other active cancers except certain non-melanoma skin cancers or carcinoma in situ
- Active HIV infection
- Uncontrolled concurrent illness including infections, heart failure, unstable angina, arrhythmias, psychiatric illness, or social issues affecting compliance
- Pregnant or breastfeeding women
- Diagnosis of myelodysplasia
- Active hepatitis B or C infection confirmed by positive viral load
AI-Screening
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Trial Site Locations
Total: 1 location
1
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
6
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