Genetically Engineered Lymphocyte Therapy in Treating Patients With Lymphoma That is Resistant or Refractory to Chemotherapy

September 27, 2015 updated by: Han weidong, Chinese PLA General Hospital

Pilot Study of Redirected Autologous T Cells Transduced to Express A CD20-Specific Chimeric Immunoreceptor in Patient With Chemotherapy Resistant or Refractory CD20+ Leukemia and Lymphoma

RATIONALE: Placing a gene that has been created in the laboratory into white blood cells may make the body build an 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 resistant 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-CD20 vector (referred to as CART-20 cells).

II. Determine duration of in vivo survival of CART-20 cells. RT-PCR analysis of whole blood will be used to detect and quantify survival of CART-20 TCR zeta:4-1BB over time.

SECONDARY OBJECTIVES:

I. For patients with detectable disease, measure anti-tumor response due to CART-20 cell infusions.

II. Estimate relative trafficking of CART-20 cells to tumor in bone marrow and lymph nodes.

III. For patients with stored or accessible tumor cells (such as patients with active CLL, ALL, etc) determine tumor cell killing by CART-20 cells in vitro.

IV. Determine if cellular or humoral host immunity develops against the murine anti-CD20, and assess correlation with loss of detectable CART-20 (loss of engraftment).

V. Determine the relative subsets of CART-20 T cells (Tcm, Tem, and Treg).

OUTLINE: Patients are assigned groups according to order of enrollment.

Patients receive anti-CD20-CAR lentivirus vector-transduced autologous T cells with 41BB-gamma vector for 3-5 days 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)

50

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 Contact

Study Contact Backup

  • Name: Bo jian, doctor
  • Phone Number: +86-10-13801257802
  • Email: boj301@sina.com

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100853
        • Recruiting
        • Biotherapeutic Department of Chinese PLA General Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Han weidong, Doctor
        • Sub-Investigator:
          • Bo Jian, Doctor
        • Sub-Investigator:
          • Wang Yao, Master

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 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • •Male and female subjects with CD20+ 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

    • CD20+ leukemia or lymphoma
    • ALL in CR2 or CR3 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 CD20+:
    • 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 as initial therapy will be eligible.
    • Mantle cell lymphoma:
    • Beyond 1st CR 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 CD20+:
    • 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/AST < 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/CD28 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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: anti-CD20-CAR T cell
Arm 1 Patients receive anti-CD20-CAR lentiviral vector-transduced autologous T cells with 41BB vector for 3-5 days in the absence of disease progression or unacceptable toxicity.
Biological: anti-CD20-CAR vector-transduced autologous T cells
anti-CD20-CAR vector-transduced autologous T cells
Other: genetically engineered lymphocyte therapy
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-20 cell infusions
Time Frame: Baseline and post-infusion
Baseline and post-infusion

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

January 1, 2013

Primary Completion (Anticipated)

May 1, 2017

Study Completion (Anticipated)

October 1, 2018

Study Registration Dates

First Submitted

November 23, 2012

First Submitted That Met QC Criteria

November 27, 2012

First Posted (Estimate)

November 28, 2012

Study Record Updates

Last Update Posted (Estimate)

September 29, 2015

Last Update Submitted That Met QC Criteria

September 27, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHN-PLAGH-BT-001

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.

Clinical Trials on Recurrent Adult Diffuse Large Cell Lymphoma

Clinical Trials on anti-CD20-CAR vector-transduced autologous T cells

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in New Zealand

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe