Hematopoietic/Lymphoid Cancer, Mantle Cell Lymphoma, Non-hodgkin Lymphoma,B Cell
Conditions
Keywords
chimeric antigen receptor, immunotherapy, T lymphocyte, mantle cell lymphoma
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).
Interventions
BIOLOGICALanti-CD19-CAR vector-transduced T cells
Sponsors
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Clinical responses to CART-19 cell therapy | Until 24 weeks |
Countries
China
Contacts
Primary ContactQuanshun Wang, Dr.
Outcome results
None listed