Activated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL, and CLL (SAGAN) (SAGAN)
Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Acute Lymphocytic Leukemia
About this trial
This is an interventional treatment trial for Non-Hodgkin Lymphoma focused on measuring chronic Lymphocytic Leukemia, refractory, recurrent, aggressive B-cell Lymphoma, CD19, Non-Hodgkin Lymphoma, CD28, CD137, 4-1BB, acute lymphocytic leukemia
Eligibility Criteria
Inclusion Criteria:
PROCUREMENT
Referred patients (or respective donors) will initially be consented for procurement of blood for generation of the transduced ATL. Eligibility criteria at this stage include:
- Diagnosis of recurrent B-cell lymphoma or leukemia (ALL or CLL), or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory aggressive B-cell lymphoma with a treatment plan that will include high dose therapy and autologous stem cell transplantation.
- CD19-positive tumor (result can be pending at this time).
- Age <= 75 years. The first 3 patients treated on the study should be adults (>= 18 years).
- Hgb greater than or equal to 7.0 (can be a transfused value)
- If pheresis required to collect blood:
- Creatinine < 1.5 x upper limit normal
- AST <1.5 × upper limit normal
- PT and APTT <1.5 × upper limit normal
- Informed consent explained to, understood by and signed by patient/guardian (and donor, where applicable). Patient/guardian given copy of informed consent.
TREATMENT
- Diagnosis of recurrent B-cell lymphoma leukemia (ALL or CLL), or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory aggressive B-cell lymphoma with a treatment plan that will include high dose therapy and autologous stem cell transplantation.
- CD19-positive tumor.
- Age <= 75 years. The first 3 patients treated on the study should be adults (>= 18 years).
- Bilirubin less than 3 times the upper limit of normal.
- AST less than 5 times the upper limit of normal.
- Estimated GFR > 50 mL/min
- Pulse oximetry of > 90% on room air
- Karnofsky or Lansky score of > 60%.
- Recovered from acute toxic effects of prior chemotherapy at least one week before entering this study. PD1/PDL1 inhibitors will be allowed if medically indicated.
- Available autologous or syngeneic activated peripheral blood T cell products (CD28ζ and CD28/CD137ζ) with more than or equal to 15% expression of CD19.CAR determined by flow cytometry.
- Life expectancy of greater than 12 weeks.
- Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
- Patients or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form.
Exclusion Criteria:
PROCUREMENT
- Active infection requiring antibiotics.
- No history of other cancer (except non-melanoma skin cancer or in situ breast cancer or cervix cancer) unless the tumor was successfully treated with curative intent at least 2 years before trial entry.
TREATMENT
- Currently receiving any investigational agents or received any tumor vaccines within the previous 6 weeks. (Note treatment with PD1/PDL1 inhibitors is allowed.)
- History of hypersensitivity reactions to murine protein-containing products.
- Pregnant or lactating.
- Tumor in a location where enlargement could cause airway obstruction.
- Active infection with HIV or HTLV.
Sites / Locations
- Houston Methodist HospitalRecruiting
- Texas Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Dose Escalation: CD19 CAR T Cells for B-cell ALL
Dose Expansion: CD19 CAR T Cells for B-cell ALL
Dose Escalation: CD19 CAR T Cells for B-cell NHL/CLL
Dose Expansion: CD19 CAR T Cells for B-cell NHL/CLL
Each patient will receive a dose of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.
Each patient will receive the maximum tolerated dose (MTD) of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.
Each patient will receive a dose of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.
Each patient will receive the maximum tolerated dose (MTD) of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.