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CART-19 Immunotherapy in Mantle Cell Lymphoma

Primary Purpose

Hematopoietic/Lymphoid Cancer, Non-hodgkin Lymphoma,B Cell, Mantle Cell Lymphoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

anti-CD19-CAR vector-transduced T cells

About this trial

This is an interventional treatment trial for Hematopoietic/Lymphoid Cancer focused on measuring chimeric antigen receptor, immunotherapy, T lymphocyte, mantle cell lymphoma

Eligibility Criteria

50 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male and female with CD19+ relapsed or refractory MCL, and with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled.
Not eligible or appropriate for conventional allogeneic SCT
Patients who achieve only a partial response to FCR(fludarabine, cyclophosphamide and Rituxan) as initial therapy will be eligible.
Beyond 1st CR (complete remission) with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT
Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc...)
Relapsed after prior autologous SCT
Residual disease after primary therapy and not eligible for autologous SCT
Relapsed after prior autologous SCT
Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate of conventional allogeneic or autologous SCT
Expected survival > 12 weeks
Creatinine < 2.5 mg/dl
ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal
Bilirubin < 2.0 mg/dl
Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy
Adequate venous access for apheresis, and no other contraindications for leukapheresis
Voluntary informed consent is given

Exclusion Criteria:

• Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.
Uncontrolled active infection
Active hepatitis B or hepatitis C infection
Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
Previously treatment with any gene therapy products
Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation
Any uncontrolled active medical disorder that would preclude participation as outlined
HIV infection

Sites / Locations

Department of Hematology of Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Anti-CD19 CAR T cells

Arm Description

Patients receive anti-CD19-CAR retroviral vector-transduced autologous or donor-derived T cells on d1-5 in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Occurrence of study related adverse events

defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to the study.

Secondary Outcome Measures

Clinical responses to CART-19 cell therapy

Full Information

NCT ID

NCT02081937

First Posted

March 6, 2014

Last Updated

March 10, 2014

Sponsor

Chinese PLA General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02081937

Brief Title

CART-19 Immunotherapy in Mantle Cell Lymphoma

Official Title

Anti-CD19 Chimeric Antigen Receptor Modified T Cells Infusion in Mantle Cell Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

March 2014

Overall Recruitment Status

Unknown status

Study Start Date

March 2014 (undefined)

Primary Completion Date

December 2018 (Anticipated)

Study Completion Date

December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese PLA General Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Patients receive anti-CD19-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells over a period of 4 or 5 consecutive days in an escalating dose. After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 10 years.

Detailed Description

PRIMARY OBJECTIVES: I. Determine the safety and efficacy of the chimeric antigen receptor T cells transduced with the anti-CD19 (cluster of differentiation antigen 19 ) vector (referred to as CART-19 cells) in elderly patients with MCL. II. Determine duration of in vivo survival of CART-19 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-19 TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time. SECONDARY OBJECTIVES: For patients with detectable disease, measure anti-tumor response due to CART-19 cell infusions. Estimate relative trafficking of CART-19 cells to tumor in bone marrow and lymph nodes. Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable CART-19 (loss of engraftment).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematopoietic/Lymphoid Cancer, Non-hodgkin Lymphoma,B Cell, Mantle Cell Lymphoma

Keywords

chimeric antigen receptor, immunotherapy, T lymphocyte, mantle cell lymphoma

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

2 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Anti-CD19 CAR T cells

Arm Type

Experimental

Arm Description

Patients receive anti-CD19-CAR retroviral vector-transduced autologous or donor-derived T cells on d1-5 in the absence of disease progression or unacceptable toxicity.

Intervention Type

Biological

Intervention Name(s)

anti-CD19-CAR vector-transduced T cells

Other Intervention Name(s)

Genetically engineered lymphocyte therapy

Primary Outcome Measure Information:

Title

Occurrence of study related adverse events

Description

defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to the study.

Time Frame

Until 2 years

Secondary Outcome Measure Information:

Title

Clinical responses to CART-19 cell therapy

Time Frame

Until 24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male and female with CD19+ relapsed or refractory MCL, and with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled. Not eligible or appropriate for conventional allogeneic SCT Patients who achieve only a partial response to FCR(fludarabine, cyclophosphamide and Rituxan) as initial therapy will be eligible. Beyond 1st CR (complete remission) with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc...) Relapsed after prior autologous SCT Residual disease after primary therapy and not eligible for autologous SCT Relapsed after prior autologous SCT Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate of conventional allogeneic or autologous SCT Expected survival > 12 weeks Creatinine < 2.5 mg/dl ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal Bilirubin < 2.0 mg/dl Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy Adequate venous access for apheresis, and no other contraindications for leukapheresis Voluntary informed consent is given Exclusion Criteria: • Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion. Uncontrolled active infection Active hepatitis B or hepatitis C infection Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary Previously treatment with any gene therapy products Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation Any uncontrolled active medical disorder that would preclude participation as outlined HIV infection

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Quanshun Wang, Dr.

Phone

8610-66939486

wqs63@sohu.com

Facility Information:

Facility Name

Department of Hematology of Chinese PLA General Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100853

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yu Zhao, Dr.

Phone

8610-55499304

zhaoyu301@126.com

First Name & Middle Initial & Last Name & Degree

Yu Zhao, Dr.

First Name & Middle Initial & Last Name & Degree

Honghua Li, Dr.

12. IPD Sharing Statement

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CART-19 Immunotherapy in Mantle Cell Lymphoma

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