This phase I trial studies the side effects and best dose of cellular immunotherapy following chemotherapy in treating patients with non-Hodgkin lymphomas, chronic lymphocytic leukemia, or B-cell prolymphocytic leukemia that has come back. Placing a modified gene into white blood cells may help the body build an immune response to kill cancer cells.
PRIMARY OBJECTIVES: I. To assess the safety of adoptive therapy using ex vivo expanded autologous memory T cells (central memory T cells \[Tcm\] or naive and memory T-cells \[Tn/mem\]) that are enriched and genetically modified to express a cluster of differentiation (CD)19-specific, hinged optimized, CD28-costimulatory chimeric antigen receptor (CAR) as well as a truncated human epidermal growth factor receptor (EGFR) (CD19R\[EQ\]28zeta/truncated EGFR \[EGFRt\]+ Tcm or CD19R\[EQ\]28zeta/EGFRt+ Tn/mem) shortly following lymphodepletion for adults with recurrent/progressive/residual CD19 + B-cell lymphoproliferative neoplasms (non-Hodgkin lymphoma \[NHL\], chronic lymphocytic leukemia \[CLL\]/prolymphocytic leukemia \[PLL\]) and who are not eligible for or decline City of Hope (COH) Institutional Review Board (IRB) Protocol Number (No.) 13277. II. To determine the recommended Phase II dose (RP2D) in the two Tn/mem strata (NHL; CLL/PLL). SECONDARY OBJECTIVE: I. To study antitumor activity of CD19R(EQ)CD28zeta/EGFRt+Tcm or CD19R\[EQ\]28zeta/EGFRt+ Tn/mem (e.g., detection of CAR+ T cells, B cells, and tumor burden). OUTLINE: This is a dose-escalation study of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing enriched T cells (T-cell infusion). Participants are assigned to 1 of 2 groups based on disease status. GROUP I (NON-HODGKIN LYMPHOMA \[NHL\]): LYMPHODEPLETING REGIMEN: Patients receive a chemotherapy regimen based on disease type and extent of disease comprising of cyclophosphamide, bendamustine hydrochloride, fludarabine phosphate, etoposide. CELLULAR IMMUNOTHERAPY: Beginning 3-10 days later after lymphodepletion, patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes IV over 10-15 minutes on day 0. Patients with relapsed, residual or progressive disease may receive an optional second infusion of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes \>= 28 days post T cell infusion. GROUP II (CHRONIC LYMPHOCYTIC LEUKEMIA \[CLL\] AND/OR PROLYMPHOCYTIC LEUKEMIA \[PLL\]): LYMPHODEPLETING REGIMEN: Patients receive a chemotherapy regimen based on disease type and extent of disease comprising of cyclophosphamide, bendamustine hydrochloride, fludarabine phosphate, etoposide. CELLULAR IMMUNOTHERAPY: Beginning 3-10 days later after lymphodepletion, patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes IV over 10-15 minutes on day 0. Patients with relapsed, residual or progressive disease may receive an optional second infusion of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes \>= 28 days post T cell infusion. After completion of study treatment, patients are followed up at every 2 days for 14 days, weekly for 1 month, monthly for 1 year, and then yearly for at least 15 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
37
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Toxicity profile of T-cell infusion as defined by all toxicities associated with T cells at the probably or definite levels
Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0) and modified cytokine release syndrome grading as applicable. Tables will summarize all toxicities and side effects by dose, time post treatment (first 28 days, days 29-60, 61-100, \>100 days), organ and severity.
Time frame: Up to 15 years
Dose-limiting toxicity rate at the recommended phase II dose assessed using CTCAE v4.0
Rates and associated 95% Clopper and Pearson binomial confidence limits will be estimated.
Time frame: Up to 28 days
Detection of transferred T cells in the circulation for at least 28 days by quantitative-polymerase chain reaction
Rates and associated 95% Clopper and Pearson binomial confidence limits will be estimated.
Time frame: 28 days
Disease response by physical exam, lab data, radiographic imaging and, in the case of stratum 2 (chronic lymphocytic leukemia/prolymphocytic leukemia) and leukemic phase non-Hodgkin lymphoma patients by flow cytometry and bone marrow biopsy
Rates and associated 95% Clopper and Pearson binomial confidence limits will be estimated.
Time frame: Up to 15 years
CD19 B cell aplasia/immunoglobulin G levels
Normal CD19+ B cell levels and immunoglobulin G levels will be reported over the study period using both descriptive statistics and graphical methods.
Time frame: Up to 15 years
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