CART-19 Immunotherapy in Mantle Cell Lymphoma

Chinese PLA General Hospital (301 Hospital)

Status and phase: Unknown; Phase 2; Phase 1

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

Treatments: Biological: anti-CD19-CAR vector-transduced T cells

Study type: Interventional

Funder types: Other

Identifiers

NCT02081937

CN301-XYK-CAR001

Details and patient eligibility

About

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.

Full 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).

Enrollment: 2 estimated patients

Sex: All

Ages: 50 to 80 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

Anti-CD19 CAR T cells

Experimental group

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.

Treatment:

Biological: anti-CD19-CAR vector-transduced T cells