CART-19 Immunotherapy in Mantle Cell Lymphoma

NCT ID: NCT02081937

Last Updated: 2014-03-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2019-12-31

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).

Conditions

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

Study Design

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

Study Groups

Anti-CD19 CAR T cells

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.

Group Type: EXPERIMENTAL

anti-CD19-CAR vector-transduced T cells

Intervention Type: BIOLOGICAL

Interventions

anti-CD19-CAR vector-transduced T cells

Intervention Type: BIOLOGICAL

Other Intervention Names

Genetically engineered lymphocyte therapy

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Quanshun Wang

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Hematology of Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Quanshun Wang, Dr.

Role: CONTACT

wqs63@sohu.com

8610-66939486

Facility Contacts

Yu Zhao, Dr.

Role: primary

zhaoyu301@126.com

8610-55499304

Other Identifiers

CN301-XYK-CAR001

Identifier Type: -

Identifier Source: org_study_id