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

B-cell Lymphomas Clinical Trial

— 4SCAR19273  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02247609
• Other study ID #: 19273-4SCAR
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: September 17, 2014
• Last updated: October 16, 2014
• Start date: January 2014
• Est. completion date: October 2017

Study information

• Verified date: January 2014
• Source: Peking University
• Contact: Jun Zhu, MD
• Phone: +86-10-88196596
• Email: zj[@]bjcancer.org
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 2017
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• B-cell Lymphomas
• Lymphoma
• Lymphoma, B-Cell

Intervention

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

Locations

Country	Name	City	State
China	Peking University Cancer Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University	University of Florida

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with adverse events.	Determine the toxicity profile of the 4th generation CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.	2 years.	Yes
Secondary	Survival time of Anti-CD19 CAR T cells in vivo.	Measure the survival of 4th generation CAR T cells transduced with the anti-CD19 lentiviral vector.	2 years.	No
Secondary	Response rates to the 4th generation CAR T cells.	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.	No
Secondary	Survival time of the patients.	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.	No