Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma (MatchCART)

March 14, 2017 updated by: Chengzhi, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine

A Phase I/II Study of Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 Chimeric Antigen Receptor T-Cells in Patients With Refractory CD19+ B-lineage Leukemia/Lymphoma

This is a single-arm open-label phase I/II study to determine the relative superiority of αCD19-TCRζ-CD28 and αCD19-TCRζ-CD137 CAR-T Cells in safety, efficacy and engraftment potential in patients with CD19+ B-lineage leukemia and lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. In this trial, all subjects will be competitively infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number to test a hypothesis that CD137-costimulation can promote the persistence and engraftment of CAR-T cells and this superiority can lead to improved progression-free survival.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Primary objectives

1. To determine the safety and feasibility of adoptive transfer of T cells modified to express CD19-specific chimeric antigen receptor (CD19CAR) for treatment of leukemia and lymphoma

Secondary objectives

  1. To measure the efficacy of anti-tumor responses after CD19CAR T cell infusion
  2. To determine if CD19CAR T cells engineered with 4-1BB signaling domain is superior to that with CD28 signaling domain for their homing and persistence after CD19CAR T cell infusion

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
    • Henan
      • Zhengzhou, Henan, China
        • Recruiting
        • Henan Province of TCM
        • Contact:
          • Zhi Cheng, M.D.

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

5 years to 70 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 5 Years to 70 Years, Male and female;
  2. Expected survival > 12 weeks;
  3. Performance score 0-2;

  4. Histologically confirmed as CD19-positive lymphoma/leukemia 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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Mixed CD19CAR transfer
All subjects will be infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number
Drug: Cyclophosphamide
Drug: Fludarabine
Biological: anti-CD19 CAR-T
Ex vivo-expanded autologous T cells modified to express CD19 CAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety (incidence of adverse events defined as dose-limited toxicity)
Time Frame: 30 days
30 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 1 year
1 year
Overall complete remission rate
Time Frame: 8 weeks
8 weeks
Survival of CAR T cells in circulation measured by flow cytometry and PCR
Time Frame: 1 year
1 year
Duration of remission
Time Frame: 1 year
1 year

Collaborators and Investigators

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

Sponsor

The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine

Collaborators

Xuzhou Medical University
Xinqiao Hospital of Chongqing

Investigators

  • Principal Investigator: Zhi Cheng, M.D., The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine

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

February 1, 2016

Primary Completion (ANTICIPATED)

December 1, 2017

Study Completion (ANTICIPATED)

December 1, 2019

Study Registration Dates

First Submitted

February 14, 2016

First Submitted That Met QC Criteria

February 14, 2016

First Posted (ESTIMATE)

February 19, 2016

Study Record Updates

Last Update Posted (ACTUAL)

March 16, 2017

Last Update Submitted That Met QC Criteria

March 14, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DHHUTCM20160106

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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