Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by CART19

Recurrent Mantle Cell Lymphoma Clinical Trial

— CART19  

Official title:

Clinical Study of Chimeric CD(Cluster of Differentiation)19 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory B-cell Leukemias and Lymphomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01864889
• Other study ID #: CHN-PLAGH-BT-005
• Status: Recruiting
• Phase: N/A
• First received: May 20, 2013
• Last updated: January 26, 2016
• Start date: April 2013
• Est. completion date: April 2017

Study information

• Verified date: January 2016
• Source: Chinese PLA General Hospital
• Contact: weidong han, Dr.
• Phone: 86-10-13651392893
• Email: hanwdrsw[@]sina.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.

PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in treating patients with B-cell leukemia or lymphoma that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to chemotherapy.

Description:

PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19 (cluster of differentiation antigen 19 ) vector (referred to as CART-19 cells).

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:

I. For patients with detectable disease, measure anti-tumor response due to CART-19 cell infusions.

II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of CART-19 TCR zeta:CD137 and TCR zeta cells over time.

III. Estimate relative trafficking of CART-19 cells to tumor in bone marrow and lymph nodes.

IV. For patients with stored or accessible tumor cells (such as patients with active chronic lymphocytic leukemia(CLL), acute lymphocytic leukemia (ALL), etc) determine tumor cell killing by CART-19 cells in vitro.

V. 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).

VI. Determine the relative subsets of CART-19 T cells (Tcm, Tem, and Treg).

OUTLINE: Patients are assigned to 1 group according to order of enrollment.

Patients receive anti-CD19-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 90 Years

Eligibility

Inclusion Criteria:

• Male and female subjects with CD19+ B cell malignancies in patients 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

• CD19+ leukemia or lymphoma

• ALL in CR2(second complete remission) or CR3(third complete remission) and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor

• Follicular lymphoma, previously identified as CD19+:

• At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy

• Stage III-IV disease

• Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year)

• Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc)

• CLL:

• At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy. Patients with high risk disease manifested by deletion chromosome 17p will be eligible if they fail to achieve a CR to initial therapy or progress within 2 years of 1 prior

• Less than 2 years between last chemotherapy and progression (i.e. most recent progression free interval < 2 years)

• 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.

• Mantle cell lymphoma:

• 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

• B-cell prolymphocytic leukemia (PLL) with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT

• Diffuse large cell lymphoma, previously identified as CD19+:

• 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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Acute Lymphoblastic Leukemia in Remission
• B-cell Adult Acute Lymphoblastic Leukemia
• B-cell Chronic Lymphocytic Leukemia
• Hematopoietic/Lymphoid Cancer
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Prolymphocytic
• Lymphoma
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Prolymphocytic Leukemia
• Recurrent Adult Diffuse Large Cell Lymphoma
• Recurrent Grade 1 Follicular Lymphoma
• Recurrent Grade 2 Follicular Lymphoma
• Recurrent Grade 3 Follicular Lymphoma
• Recurrent Mantle Cell Lymphoma
• Refractory Chronic Lymphocytic Leukemia
• Stage III Adult Diffuse Large Cell Lymphoma
• Stage III Chronic Lymphocytic Leukemia
• Stage III Grade 1 Follicular Lymphoma
• Stage III Grade 2 Follicular Lymphoma
• Stage III Grade 3 Follicular Lymphoma
• Stage III Mantle Cell Lymphoma
• Stage IV Adult Diffuse Large Cell Lymphoma
• Stage IV Chronic Lymphocytic Leukemia
• Stage IV Grade 1 Follicular Lymphoma
• Stage IV Grade 2 Follicular Lymphoma
• Stage IV Grade 3 Follicular Lymphoma
• Stage IV Mantle Cell Lymphoma

Intervention

Biological:
• anti-CD19-CAR vector-transduced T cells
genetically engineered lymphocyte therapy

Locations

Country	Name	City	State
China	Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	in vivo existence of CART19		1 year	Yes
Primary	Occurrence of study related adverse events	defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment	Until week 24	Yes
Secondary	Anti-tumor responses to CART-19 cell infusions		up to 24 weeks	No