Evaluation of 4th Generation Safety-designed CAR T Cells Targeting High-risk and Refractory B Cell Lymphomas (4SCAR19273)

October 16, 2014 updated by: Jun Zhu, Peking University

Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting High-risk and Refractory B Cell Lymphomas

Currently, a majority of B cell lymphomas cannot be cured by standard chemo-radiotherapy. Most B cell lymphomas express cluster of differentiation antigen 19 (CD19), which represents a very attractive target for chimeric antigen receptor (CAR)-based immune cell therapy. This study will evaluate a novel 4th generation CD19 CAR engineered with a self-withdrawal mechanism (19273-4SCAR) for both efficacy and safety in lymphoma patients.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

CD19 single chain antibody-based chimeric antigen receptor (CAR)-engineered T cells have demonstrated great clinical potential in treating chronic and acute B cell leukemias. B cell lymphomas, similar to B cell leukemias, express CD19 surface molecules, and the majority of the B cell lymphoma patients cannot be cured by standard chemo-radiotherapy. CD19 CAR-based adoptive T cell therapy is associated with an unwanted adverse effect, the loss of CD19 B cells, which results in humoral immune deficiency. This study will evaluate a novel 4th generation CD19 CAR engineered with a self-withdrawal genetic mechanism (19273-4SCAR) for both efficacy and safety in lymphoma patients. The 4th generation design of the CAR incorporates the intracellular signaling domain of cluster of differentiation antigen 27 (CD27), known to be associated with T cell activation, survival and longevity. The inducible caspase 9 self-withdrawal design allows for rapid elimination of the infused CAR T cells upon complete eradication of the tumor cells, which will be followed by the recovery of humoral immunity. Patients receiving the 19273-4SCAR T cells will be closely monitored for infusion response, tumor eradication effect, longevity of the CAR T cells, and the recovery of B cell functions after withdrawal of the CAR T cells.

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
    • Beijing
      • Beijing, Beijing, China, 100142
        • Recruiting
        • Peking University Cancer Hospital

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Relapsed or refractory CD19(+) B cell lymphoma patients proved by immuno-histochemistry (IHC) or Flow-cytometry.
  • Not eligible for autologous stem-cell transplantation (ASCT) or relapsed after ASCT.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Age≥18.
  • Pulse oximetry of > 90% on room air.
  • Adequate hepatic function, defined as alanine transaminase (ALT) <3 x upper limit of normal (ULN), aspartate aminotransferase (AST) <3 x ULN; serum bilirubin and alkaline phosphatase <2 x ULN.
  • Adequate renal function, defined as serum creatinine <2.0mg/dl.
  • Adequate heart function with LVEF≥50%
  • Hb≥80g/L
  • Measurable disease can be identified.
  • Life expectancy ≥3 months.
  • Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 1 year after the study is concluded. The male partner should use a condom.
  • Patients must sign an informed consent.

Exclusion Criteria:

  • Uncontrolled active infection.
  • Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV).
  • HIV positive
  • Pregnant or lactating.
  • Currently enrolled in another clinical trial.
  • Concurrent use of systemic steroids.

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: CAR T cells
Autologous 4th generation anti-CD19-CAR T cells
Genetic: Anti-CD19 CAR T cells
Autologous 4th generation withdrawable lentiviral-transduced anti-CD19-CAR T cells
Other Names:
  • 19273-4SCAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with adverse events.
Time Frame: 2 years.
Determine the toxicity profile of the 4th generation CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
2 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival time of Anti-CD19 CAR T cells in vivo.
Time Frame: 2 years.
Measure the survival of 4th generation CAR T cells transduced with the anti-CD19 lentiviral vector.
2 years.
Response rates to the 4th generation CAR T cells.
Time Frame: 2 years.
Describe the response rates of patients treated with 4th generation CAR T cells, including partial remission (PR), complete remission (CR), stable disease (SD) and progressive disease (PD).
2 years.
Survival time of the patients.
Time Frame: 2 years.
Evaluate the survival time of the patients treated with the 4th generation CAR T cells, including progression free survival (PFS) and overall survival (OS).
2 years.

Collaborators and Investigators

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

Sponsor

Peking University

Collaborators

University of Florida

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, 2014

Primary Completion (Anticipated)

October 1, 2016

Study Completion (Anticipated)

October 1, 2017

Study Registration Dates

First Submitted

September 17, 2014

First Submitted That Met QC Criteria

September 21, 2014

First Posted (Estimate)

September 25, 2014

Study Record Updates

Last Update Posted (Estimate)

October 20, 2014

Last Update Submitted That Met QC Criteria

October 16, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19273-4SCAR

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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