Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma (MeCAR)

February 25, 2019 updated by: Qingzhu Jia, M.D., Xinqiao Hospital of Chongqing

A Two-Arm, Single-Center, Open-Label Pilot Study of IL-2 Programmed or IL-7/IL-15 Programmed Anti-CD19:TCRz:CD28 T-cells in Patient With CD19-Positive Lymphoma That is Resistant or Refractory to Chemotherapy

The goal of this clinical trial is to study how approaches for manufacturing chimeric antigen receptor (CAR)-modified T (CAR-T) cells affect their in vivo persistence and therapeutic efficacy against B lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Among the many emerging immunotherapeutic approaches, clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. CARs combine the variable region of an antibody with T-cell signaling moieties to confer T-cell activation with the targeting specificity of an antibody. Thus, CARs are not MHC-restricted so they are not vulnerable to MHC down regulation by tumors. However, defined by the activation and contraction program of their mother cells, the persistency and function of CAR-T cells are also restricted by the protocol of manufacturing. Previous clinical studies largely utilized interleukin-2 (IL-2) for the ex vivo expansion of CAR-T cells, which preferentially generate CAR-T cells with characteristics of terminally differentiated effector cells. Our preliminary data indicated that two common gamma chain cytokines, IL-7 and IL-15, can help to selectively expand CAR-T cells with various memory phenotypes. CAR-T Cells prepared under this condition resulted in improved therapeutic efficacy in preclinical animal models. This clinical investigation is to test a hypothesis whether IL-7/IL-15-programmed anti-CD19 CAR-T cells persist longer in lymphoma patients after infusion and whether the persistency of CAR-T cells can lead to improved anti-lymphoma efficacy.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Primary Objectives

  1. To determine the safety and feasibility of CD19.CAR-T cells manufactured through IL-7/IL-15-mediated expansion or IL-2-mediated expansion
  2. To determine in vivo dynamics and persistency of IL-7/IL-15 programmed CD19.CAR-T cells.
  3. To determine the efficacy of IL-7/IL-15 programmed CD19.CAR-T cells in treating patients with CD19-positive lymphoma

Secondary Objectives

  1. To determine whether the IL-7/IL-15 programmed CD19.CAR-T cells are superior to the IL-2 programmed cells as measured by their in vivo persistence post infusion
  2. To determine whether the IL-7/IL-15 programmed CD19.CAR-T cells are superior to the IL-2 programmed cells as measured by their efficacy in lymphoma therapy
  3. To assess the dynamics of intratumoral infiltration of CD19.CAR-T cells.
  4. To correlate the subsets and differentiation of CD19.CAR-T cells to observed anti-tumor efficacy

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Chongqing
      • ChongQing, Chongqing, China, 400000
        • Recruiting
        • Department of Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 18 Years to 70 Years, Male and female;
  2. Expected survival > 12 weeks;
  3. Performance score 0-2;

  4. Histologically confirmed as CD19-positive lymphoma and who meet one of the following conditions;

    • Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
    • Disease recurrence after stem cell transplantation;
    • Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy
  5. Creatinine < 2.5 mg/dl;
  6. ALT/AST < 3x normal;
  7. Bilirubin < 2.0 mg/dl;
  8. Adequate venous access for apheresis, and no other contraindications for leukapheresis;
  9. Take contraceptive measures before recruit to this trial;
  10. Written voluntary informed consent is given.

Exclusion Criteria:

  1. Patients with symptoms of central nervous system
  2. Accompanied by other malignant tumor
  3. Active hepatitis B or C, HIV infection
  4. Any other diseases could affect the outcome of this trial
  5. Suffering severe cardiovascular or respiratory disease
  6. Poorly controlled hypertension
  7. A history of mental illness and poorly controlled
  8. Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
  9. Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
  10. Reaching a steady dose if receiving anticoagulant therapy before assignment
  11. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
  12. Pregnant or lactating women
  13. Subject suffering disease affects the understanding of informed consent or comply with study protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IL-2 programmed CD19.CAR-T cells
Administrated with IL-2 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients
Drug: CD19.CAR-T cells
Retroviral vector-transduced autologous T cells to express CD19-specific CARs
Other Names:
  • DSCAR01
Experimental: IL-7/IL-15 programmed CD19.CAR-T cells
Administrated with IL-7/IL-15 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients
Drug: CD19.CAR-T cells
Retroviral vector-transduced autologous T cells to express CD19-specific CARs
Other Names:
  • DSCAR01

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase 1: Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
Time Frame: 4 weeks
4 weeks
Phase 2: Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm
Time Frame: 8 weeks
8 weeks
Phase 2: Comparison of overall complete remission rate for the two arms
Time Frame: One year
One year

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: One year
One year
Duration of CAR-positive T cells in circulation
Time Frame: 6 months
6 months
Total number of CAR-positive T cells infiltrated into lymphoma tissue
Time Frame: 6 months
6 months
Duration of remission
Time Frame: One year
One year
Minimum residual disease negative remission rate
Time Frame: 8 weeks
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xinqiao Hospital of Chongqing

Collaborators

Xuzhou Medical University
Shanghai Changzheng Hospital
Hrain Biotechnology Co., Ltd.

Investigators

  • Principal Investigator: Bo Zhu, M.D., Ph.D., Department of Cancer of Xinqiao Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Anticipated)

June 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

November 18, 2015

First Submitted That Met QC Criteria

January 11, 2016

First Posted (Estimate)

January 12, 2016

Study Record Updates

Last Update Posted (Actual)

February 27, 2019

Last Update Submitted That Met QC Criteria

February 25, 2019

Last Verified

April 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20151117

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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