Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by CART19 (CART19)

January 26, 2016 updated by: Han weidong, Chinese PLA General Hospital

Clinical Study of Chimeric CD(Cluster of Differentiation)19 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory B-cell Leukemias and Lymphomas

RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.

PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in treating patients with B-cell leukemia or lymphoma that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to chemotherapy.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19 (cluster of differentiation antigen 19 ) vector (referred to as CART-19 cells).

II. Determine duration of in vivo survival of CART-19 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-19 TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time.

SECONDARY OBJECTIVES:

I. For patients with detectable disease, measure anti-tumor response due to CART-19 cell infusions.

II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of CART-19 TCR zeta:CD137 and TCR zeta cells over time.

III. Estimate relative trafficking of CART-19 cells to tumor in bone marrow and lymph nodes.

IV. For patients with stored or accessible tumor cells (such as patients with active chronic lymphocytic leukemia(CLL), acute lymphocytic leukemia (ALL), etc) determine tumor cell killing by CART-19 cells in vitro.

V. Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable CART-19 (loss of engraftment).

VI. Determine the relative subsets of CART-19 T cells (Tcm, Tem, and Treg).

OUTLINE: Patients are assigned to 1 group according to order of enrollment.

Patients receive anti-CD19-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years.

Study Type

Interventional

Enrollment (Anticipated)

12

Phase

  • Not Applicable

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
    • Beijing
      • Beijing, Beijing, China, 100853
        • Recruiting
        • Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
        • Contact:

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 90 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male and female subjects with CD19+ B cell malignancies in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled

    • CD19+ leukemia or lymphoma
    • ALL in CR2(second complete remission) or CR3(third complete remission) and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor
    • Follicular lymphoma, previously identified as CD19+:
    • At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy
    • Stage III-IV disease
    • Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year)
    • Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc)
    • CLL:
    • At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy. Patients with high risk disease manifested by deletion chromosome 17p will be eligible if they fail to achieve a CR to initial therapy or progress within 2 years of 1 prior
    • Less than 2 years between last chemotherapy and progression (i.e. most recent progression free interval < 2 years)
    • Not eligible or appropriate for conventional allogeneic SCT
    • Patients who achieve only a partial response to FCR(fludarabine, cyclophosphamide and Rituxan) as initial therapy will be eligible.
    • Mantle cell lymphoma:
    • Beyond 1st CR (complete remission) with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT
    • Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc...)
    • Relapsed after prior autologous SCT
    • B-cell prolymphocytic leukemia (PLL) with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT
    • Diffuse large cell lymphoma, previously identified as CD19+:
    • Residual disease after primary therapy and not eligible for autologous SCT
    • Relapsed after prior autologous SCT
    • Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate of conventional allogeneic or autologous SCT
    • Expected survival > 12 weeks
    • Creatinine < 2.5 mg/dl
    • ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal
    • Bilirubin < 2.0 mg/dl
    • Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy
    • Adequate venous access for apheresis, and no other contraindications for leukapheresis
    • Voluntary informed consent is given

Exclusion Criteria:

  • 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
    • Uncontrolled active infection
    • Active hepatitis B or hepatitis C infection
    • Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
    • Previously treatment with any gene therapy products
    • Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation
    • Any uncontrolled active medical disorder that would preclude participation as outlined
    • HIV infection

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: anti-CD19 CAR T cells
Patients receive anti-CD19-CAR retroviral vector-transduced autologous or donor-derived T cells on days 0,1, 2 in the absence of disease progression or unacceptable toxicity.
Biological: anti-CD19-CAR vector-transduced T cells
genetically engineered lymphocyte therapy
Other Names:
  • genetically engineered lymphocyte therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of study related adverse events
Time Frame: Until week 24
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
Until week 24

Secondary Outcome Measures

Outcome Measure
Time Frame
Anti-tumor responses to CART-19 cell infusions
Time Frame: up to 24 weeks
up to 24 weeks

Other Outcome Measures

Outcome Measure
Time Frame
in vivo existence of CART19
Time Frame: 1 year
1 year

Collaborators and Investigators

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

Sponsor

Chinese PLA General 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

April 1, 2013

Primary Completion (ANTICIPATED)

April 1, 2017

Study Completion (ANTICIPATED)

April 1, 2017

Study Registration Dates

First Submitted

May 20, 2013

First Submitted That Met QC Criteria

May 26, 2013

First Posted (ESTIMATE)

May 30, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

January 28, 2016

Last Update Submitted That Met QC Criteria

January 26, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHN-PLAGH-BT-005

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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