CD19-redirected Autologous Cells (CAR-CD19 T Cells)

October 13, 2016 updated by: RenJi Hospital

Autologous T Cells With a Chimeric Antigen Receptor in Patients With CD19-positive Malignant B Cell Leukemia and Lymphoma

This study is designed for determining the safety and relative engraftment levels of the redirected autologous T cells transduced with the anti-CD19 lentiviral vector in patients with CD19-positive B cell leukemia and malignant lymphoma.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

A single arm open-label pilot study is designed to determine the safety, tolerability and engraftment potential of CAR-CD19 T cells in patients with CD19-positive malignant B cell leukemia and lymphoma. All subjects will receive CAR-CD19 T cells infusion.

Primary objectives:

  1. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19 lentiviral vector (referred to as "CAR-CD19 T" cells).
  2. Determine the duration of in vivo survival of CAR-CD19 T cells.

Secondary objectives:

  1. For patients with detectable disease, measure anti-tumor response due to CAR-CD19 T cells infusions.
  2. To determine the amplification and survival of CAR-CD19 T 4-1BB:CD3ζ and CD28:CD3ζ as measured by the relative engraftment levels of CAR-CD19 T 4-1BB:CD3ζ and CD28:CD3ζ cells over time.
  3. Estimate relative trafficking of CAR-CD19 T cells to tumors in bone marrow and lymphnodes.
  4. Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable CAR-CD19 T (loss of engraftment).
  5. Determine the relative subsets of CAR-CD19 T cells.

Study Type

Interventional

Enrollment (Anticipated)

45

Phase

  • 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 Contact

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200127
        • Renji Hospital, Shanghai Jiaotong University School of Medicine
        • Contact:
        • Principal Investigator:
          • Fangyuan Chen, MD
        • Sub-Investigator:
          • Honghui Huang, MD

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 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects with documented CD19-positive malignant B cell leukemia and lymphoma.

    1. Patients aged between 18 ~ 65 with malignant B cell leukemia and lymphoma.
    2. CD19-positive B cell leukemia or lymphoma.
    3. Expected survival > 12 weeks.
    4. ECOG scores 0-1, or KPS scores > 80.
    5. Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
    6. WBC ≥ 2.5×109/L; LY ≥ 0.7×109/L; LY% ≥ 15%.
    7. Creatinine ≤ 2.0 mg/dL (176.8 μmol/L).
    8. ALT/AST ≤ 2.5 ULN.
    9. Bilirubin ≤ 2.0 mg/dL (34.2 μmol/L).
    10. Prothrombin Time (PT) : International Normalized Ratio (INR) < 1.7, or PT is at most 4 s longer than normal value.

All tests results should comply with the above criteria. No continuing supportive care is received.

Exclusion Criteria:

  • 1. CD19-negative B cell leukemia or lymphoma. 2. Feasibility assessment during screening demonstrates < 5% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to αCD3/CD28 costimulation.

    3. Pregnant or lactating women. (The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.) 4. Active hepatitis B or hepatitis C infection. 5. HIV/AIDS infection. 6. Uncontrolled active infection. 7. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.

    8. Previously treatment with any gene therapy products. 9. Allergy to immunotherapy and associated drugs. 10. Patients with heart disease that is in need of treatment or with poorly controlled hypertension determined by investigators.

    11. Patients with unstable or active ulceration or with gastrointestinal bleeding.

    12. Patients with previous or planed organ transplantation. 13. Hyponatremia with concentration of sodium in the blood < 125 mmol/L. 14. Serum potassium (baseline) < 3.5 mmol/L (Patients can take potassium supplements to recover serum potassium level prior to participating the study).

    15. Patients need anticoagulant (e.g. Warfarin or heparin). 16. Patients need long-term antiplatelet agent (Aspirin, dose > 300 mg/d; Clopidogrel, dose > 75 mg/d).

    17. Any radiotherapy conducted within 4 weeks prior to blood sampling.

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: CAR-CD19 T cells
Autologous T Cells with a CD19-redirected Chimeric Antigen Receptor. Route of administration: Intravenous injection. Lymphodepleting conditioning regimen: A combination of fludarabine and cyclophosphamide will be administered at Day -9 - Day -4.
Genetic: CAR-CD19 T cells
Initial dose: A total of 1 - 10×10^7 CAR-CD19 T cells/kg will be administered by 1 - 3 infusions. Subsequent dose will be based on the subject's response to initial dose.
Other Names:
  • CD19 Redirected Autologous Cells
Drug: Fludarabine
30 mg/m^2/day×4 days
Drug: Cyclophosphamide
500 mg/m^2/day×2 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Study related adverse events
Time Frame: 24 weeks
Occurrence of study related adverse events, defined as NCI CTC ≥ Grade 3 signs/symptoms, laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the infusion until week 24, including infusional toxicity and any toxicity possibly related to the CAR-CD19 T cells.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary engraftment endpoint
Time Frame: 2 years
Duration of in vivo survival of CAR-CD19 T cells is defined as "engraftment". The primary engraftment endpoint is the # DNA vector copies per mg blood of CAR-CD19 T cells on week 4 after the first infusion. Q-PCR for CAR-CD19 T vector sequences will also be performed after infusion at 24 hours, weekly x 4, monthly x 6, and every 3 months thereafter until any 2 sequential tests are negative documenting loss of CAR-CD19 T cells.
2 years
Anti-tumor responses
Time Frame: 2 years
Describe anti-tumor responses to CAR-CD19 T cell infusions.
2 years
Overall survival
Time Frame: 2 years
Describe overall survival and cause of death.
2 years

Collaborators and Investigators

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

Sponsor

RenJi Hospital

Collaborators

CARsgen Therapeutics Co., Ltd.

Investigators

  • Principal Investigator: Fangyuan Chen, MD, RenJi 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

October 1, 2016

Primary Completion (ANTICIPATED)

April 1, 2018

Study Completion (ANTICIPATED)

January 1, 2020

Study Registration Dates

First Submitted

October 13, 2016

First Submitted That Met QC Criteria

October 13, 2016

First Posted (ESTIMATE)

October 14, 2016

Study Record Updates

Last Update Posted (ESTIMATE)

October 14, 2016

Last Update Submitted That Met QC Criteria

October 13, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CG3001

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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