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

NCT ID: NCT02247609

Last Updated: 2014-10-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2017-10-31

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.

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.

Conditions

B-cell Lymphomas

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CAR T cells

Autologous 4th generation anti-CD19-CAR T cells

Group Type: EXPERIMENTAL

Anti-CD19 CAR T cells

Intervention Type: GENETIC

Autologous 4th generation withdrawable lentiviral-transduced anti-CD19-CAR T cells

Interventions

Anti-CD19 CAR T cells

Autologous 4th generation withdrawable lentiviral-transduced anti-CD19-CAR T cells

Intervention Type: GENETIC

Other Intervention Names

19273-4SCAR

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida

OTHER

Sponsor Role: collaborator

Peking University

OTHER

Sponsor Role: lead

Responsible Party

Jun Zhu

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jun Zhu, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University Cancer Hospital & Institute

Locations

Peking University Cancer Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jun Zhu, MD

Role: CONTACT

zj@bjcancer.org

+86-10-88196596

Facility Contacts

Jun Zhu, MD

Role: primary

zj@bjcancer.org

+86-10-88196596

Other Identifiers

19273-4SCAR

Identifier Type: -

Identifier Source: org_study_id