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

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ClinicalTrials.gov Identifier: NCT02247609
Recruitment Status : Unknown
Verified January 2014 by Jun Zhu, Peking University.
Recruitment status was:  Recruiting
First Posted : September 25, 2014
Last Update Posted : October 20, 2014
Sponsor:
Collaborator:
University of Florida
Information provided by (Responsible Party):
Jun Zhu, Peking University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
B-cell Lymphomas Genetic: Anti-CD19 CAR T cells Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting High-risk and Refractory B Cell Lymphomas
Study Start Date : January 2014
Estimated Primary Completion Date : October 2016
Estimated Study Completion Date : October 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma Scars

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 Name: 19273-4SCAR




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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. 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).

  3. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02247609


Contacts
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Contact: Jun Zhu, MD +86-10-88196596 zj@bjcancer.org

Locations
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China, Beijing
Peking University Cancer Hospital Recruiting
Beijing, Beijing, China, 100142
Contact: Jun Zhu, MD    +86-10-88196596    zj@bjcancer.org   
Principal Investigator: Jun Zhu, MD         
Sponsors and Collaborators
Peking University
University of Florida
Investigators
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Principal Investigator: Jun Zhu, MD Peking University Cancer Hospital & Institute

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Responsible Party: Jun Zhu, Director, Peking University
ClinicalTrials.gov Identifier: NCT02247609     History of Changes
Other Study ID Numbers: 19273-4SCAR
First Posted: September 25, 2014    Key Record Dates
Last Update Posted: October 20, 2014
Last Verified: January 2014
Keywords provided by Jun Zhu, Peking University:
B cell lymphoma
non-Hodgkin's lymphoma
Burkitt lymphoma
diffused large B cell lymphoma
B cell malignancy
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin