Clinical trial NCT02081937: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Hematopoietic/Lymphoid Cancer
Non-hodgkin Lymphoma,B Cell
Mantle Cell Lymphoma
Keywords: chimeric antigen receptor
immunotherapy
T lymphocyte
mantle cell lymphoma
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2014-03-07
Enrollment: 2
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Occurrence of study related adverse events
timeFrame: Until 2 years
Secondary outcomes:
measure: Clinical responses to CART-19 cell therapy
timeFrame: Until 24 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Hematology of Chinese PLA General Hospital
state: Beijing
Study officials:
References: