CART-19 Immunotherapy in Mantle Cell Lymphoma

Phase 1

• Conditions: Hematopoietic/Lymphoid Cancer; Non-hodgkin Lymphoma,B Cell; Mantle Cell Lymphoma
• Interventions: Biological: anti-CD19-CAR vector-transduced T cells

• Registration Number: NCT02081937
• Lead Sponsor: Chinese PLA General Hospital

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).

Study Timeline

• Status Verified: 2014-03
• Study Start: 2014-03
• Study First Submitted: 2014-03-06
• Study First Submitted QC: 2014-03-06
• Study First Posted: 2014-03-07
• Last Update Submitted: 2014-03-10
• Last Update Posted: 2014-03-11
• Primary Completion: 2018-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 2

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Anti-CD19 CAR T cells	anti-CD19-CAR vector-transduced 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.

Primary Outcome Measures

Name	Time	Method
Occurrence of study related adverse events	Until 2 years	defined as \>= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to the study.

Secondary Outcome Measures

Name	Time	Method
Clinical responses to CART-19 cell therapy	Until 24 weeks

Trial Locations

Locations (1)

Department of Hematology of Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China