About this trial
This phase I trial tests the safety, side effects and best dose of anti-CD19/20/22 chimeric antigen receptor (CAR) T cells (TriCAR19.20.22 T cells) and how well they work in treating patients with non-Hodgkin lymphoma, acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein, such as CD19, CD20 and CD22, on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving TriCAR19.20.22 T cells may be safe, tolerable, and/or effective in treating patients with relapsed or refractory non-Hodgkin lymphoma, ALL and CLL.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
COHORT A: Subjects must have relapsed or refractory non-Hodgkin lymphoma with lesions ≤ 5 cm, indolent lymphomas, or chronic lymphocytic leukemia without Richter's transformation
COHORT B: Subjects with lymphoid blast crisis from chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia with Richter's transformation, non-Hodgkin lymphoma with lesions > 5 cm and/or lymphoblastic lymphoma, or non-Hodgkin lymphoma with circulating lymphoma cells
Subjects must have been treated with at least two lines of therapy; subjects with prior commercial or investigational CAR T therapy targeting CD19, and/or CD20, and/or CD22 are permitted. Disease must have either progressed after the last regimen or presented failure to achieve complete remission with the last regimen
Note: Cohort assignment at discretion of principal investigator (PI) depending on patient disease/ history
Disqualifiers
Autologous transplant within 6 weeks of planned CAR-T cell infusion
Allogeneic stem cell transplant or donor lymphocyte infusion within 2 months of planned CAR-T cell infusion and patients must be off immunosuppressive agents
Subjects with live vaccines given 28 days prior to lymphodepleting (LD) chemotherapy will be excluded
Active graft versus host disease
Trial design
Parallel
Treatments tested in this trial
Autologous Anti-CD19/CD20/CD22 CAR T-cells
Biological/VaccineGiven IV
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow biopsy and aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy and aspiration
Computed Tomography
Procedure/SurgeryUndergo PET/CT
Cyclophosphamide
DrugGiven IV
Echocardiography Test
Procedure/SurgeryUndergo echocardiography
Fludarabine
DrugGiven IV
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Pheresis
Procedure/SurgeryUndergo apheresis
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Treatment groups
Trial outcomes
Primary outcomes
Dose-limiting toxicity
Adverse events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 with the exception of cytokine release syndrome (CRS). CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS.
Recommended phase 2 dose
Secondary outcomes
Incidence of adverse events (AEs)
Will be described and graded according to NCI CTCAE v 5.0. CRS will be described and graded using ASTCT Consensus Grading for CRS. Will be evaluated with descriptive statistics for the frequencies of AEs of different grades.
Overall response rate
Will be evaluated with proportions used to describe response rates.
Complete response rate
Will be evaluated with proportions used to describe response rates.
Overall survival
Will be calculated using Kaplan-Meier method, comparisons between groups will be done using the log rank test.
Sponsors and contacts
Click on the lead sponsor to view all of their trials.