Clinical Trial: Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia or B-Cell Prolymphocytic Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase I Study to Evaluate Cellular Immunotherapy Using Central Memory-Enriched T Cells Lentivirally Transduced to Express a CD19-Specific, Hinge-Optimized, CD28-Costimulatory Chimeric Receptor and a T

Brief Summary: 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.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the safety of adoptive therapy using ex vivo expanded autologous central memory T cells (Tcm) 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) shortly following lymphodepletion for adults with recurrent/progressive/residual CD19 + B-cell lymphoproliferative neoplasms (stratum 1: non-Hodgkin lymphoma [NHL], stratum 2: 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).

SECONDARY OBJECTIVES:

I. To study antitumor activity of CD19R(EQ)CD28zeta/EGFRt+Tcm (e.g., detection of Tcm, B cells, and tumor burden).

OUTLINE: This is a dose-escalation study of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells (T-cell infusion).

LYMPHODEPLETING REGIMEN: Patients receive a chemotherapy regimen based on disease type and extent of disease comprising: cyclophosphamide intravenously (IV) on days -4 and/or -3; OR bendamustine hydrochloride IV on days -4 and -3; OR fludarabine phosphate IV and cyclophosphamide IV on days -5 to -3; OR etoposide IV and cyclophosphamide IV on days -5 to -3; OR cyclophosphamide IV on days -7 and -6 followed by etoposide IV on days -5 to -3.

CELLULAR IMMUNOTHERAPY: Beginning 3-10 days later after lympho
Sponsor: City of Hope Medical Center

Current Primary Outcome:

• Toxicity profile of T-cell infusion as defined by all toxicities associated with T cells at the probably or definite levels [ Time Frame: Up to 15 years ]
  Assessed using Common Terminology Criteria for Adverse Event (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.
• Dose-limiting toxicity rate at the recommended phase II dose assessed using CTCAE v4.0 [ Time Frame: Up to 28 days ]
  Rates and associated 95% Clopper and Pearson binomial confidence limits will be estimated.

Original Primary Outcome:

• 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) [ Time Frame: Up to 15 years ]
  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.
• Dose-limiting toxicity rate at the recommended phase II dose assessed using CTCAE v4.0 [ Time Frame: Up to 28 days ]
  Rates and associated 95% Clopper and Pearson binomial confidence limits will be estimated.

Current Secondary Outcome:

• Detection of transferred T cells in the circulation for at least 28 days by quantitative-polymerase chain reaction [ Time Frame: 28 days ]
  Rates and associated 95% Clopper and Pearson binomial confidence limits will be estimated.
• Disease response by physical exam, lab data, radiographic imaging and, in the case of stratum 2 (CLL/PLL) and leukemic phase NHL patients by flow cytometry and bone marrow biopsy [ Time Frame: Up to 15 years ]
  Rates and associated 95% Clopper and Pearson binomial confidence limits will be estimated.
• CD19 B cell aplasia/immunoglobulin G levels [ Time Frame: Up to 15 years ]
  Normal CD19+ B cell levels and and immunoglobulin G levels will be reported over the study period using both descriptive statistics and graphical methods.

Original Secondary Outcome: Same as current

Information By: City of Hope Medical Center

Dates:
Date Received: May 30, 2014
Date Started: September 2014
Date Completion:
Last Updated: July 29, 2016
Last Verified: July 2016