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

Primary Purpose

B-cell Lymphomas

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Anti-CD19 CAR T cells
Sponsored by
Peking University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Lymphomas focused on measuring B cell lymphoma, non-Hodgkin's lymphoma, Burkitt lymphoma, diffused large B cell lymphoma, B cell malignancy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Peking University Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR T cells

Arm Description

Autologous 4th generation anti-CD19-CAR T cells

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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).

Full Information

First Posted
September 17, 2014
Last Updated
October 16, 2014
Sponsor
Peking University
Collaborators
University of Florida
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1. Study Identification

Unique Protocol Identification Number
NCT02247609
Brief Title
Evaluation of 4th Generation Safety-designed CAR T Cells Targeting High-risk and Refractory B Cell Lymphomas
Acronym
4SCAR19273
Official Title
Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting High-risk and Refractory B Cell Lymphomas
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Unknown status
Study Start Date
January 2014 (undefined)
Primary Completion Date
October 2016 (Anticipated)
Study Completion Date
October 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University
Collaborators
University of Florida

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Lymphomas
Keywords
B cell lymphoma, non-Hodgkin's lymphoma, Burkitt lymphoma, diffused large B cell lymphoma, B cell malignancy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAR T cells
Arm Type
Experimental
Arm Description
Autologous 4th generation anti-CD19-CAR T cells
Intervention Type
Genetic
Intervention Name(s)
Anti-CD19 CAR T cells
Other Intervention Name(s)
19273-4SCAR
Intervention Description
Autologous 4th generation withdrawable lentiviral-transduced anti-CD19-CAR T cells
Primary Outcome Measure Information:
Title
Number of patients with adverse events.
Description
Determine the toxicity profile of the 4th generation CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
Time Frame
2 years.
Secondary Outcome Measure Information:
Title
Survival time of Anti-CD19 CAR T cells in vivo.
Description
Measure the survival of 4th generation CAR T cells transduced with the anti-CD19 lentiviral vector.
Time Frame
2 years.
Title
Response rates to the 4th generation CAR T cells.
Description
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).
Time Frame
2 years.
Title
Survival time of the patients.
Description
Evaluate the survival time of the patients treated with the 4th generation CAR T cells, including progression free survival (PFS) and overall survival (OS).
Time Frame
2 years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Zhu, MD
Phone
+86-10-88196596
Email
zj@bjcancer.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Zhu, MD
Organizational Affiliation
Peking University Cancer Hospital & Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Zhu, MD
Phone
+86-10-88196596
Email
zj@bjcancer.org
First Name & Middle Initial & Last Name & Degree
Jun Zhu, MD

12. IPD Sharing Statement

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

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