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Genetically Engineered Lymphocyte Therapy in Treating Patients With Lymphoma That is Resistant or Refractory to Chemotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Chinese PLA General Hospital
Sponsor:
Information provided by (Responsible Party):
Han weidong, Chinese PLA General Hospital
ClinicalTrials.gov Identifier:
NCT01735604
First received: November 23, 2012
Last updated: March 2, 2013
Last verified: March 2013
  Purpose

RATIONALE: Placing a gene that has been created in the laboratory into white blood cells may make the body build an 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 resistant or refractory to chemotherapy.


Condition Intervention
Hematopoietic/Lymphoid Cancer
Adult Acute Lymphoblastic Leukemia in Remission
B-cell Adult Acute Lymphoblastic Leukemia
B-cell Chronic Lymphocytic Leukemia
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
Biological: anti-CD20-CAR vector-transduced autologous T cells
Other: genetically engineered lymphocyte therapy

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Redirected Autologous T Cells Transduced to Express A CD20-Specific Chimeric Immunoreceptor in Patient With Chemotherapy Resistant or Refractory CD20+ Leukemia and Lymphoma

Resource links provided by NLM:


Further study details as provided by Chinese PLA General Hospital:

Primary Outcome Measures:
  • Occurrence of study related adverse events [ Time Frame: Until week 24 ] [ Designated as safety issue: Yes ]
    defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment


Secondary Outcome Measures:
  • Anti-tumor responses to CART-20 cell infusions [ Time Frame: Baseline and post-infusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: January 2013
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: anti-CD20-CAR T cell

Arm 1 Group 1 (Patients 1-5): Patients receive anti-CD20-CAR retroviral vector-transduced autologous T cells with 41BB-gamma vector on days 0,1, 2, and 11 in the absence of disease progression or unacceptable toxicity.

Group 2 (Patients 6-10): Patients receive anti-CD20-CAR retroviral vector-transduced autologous T cells with either 41BB-gamma vector or TCR zeta vector on days 0,1, 2, and 11 in the absence of disease progression or unacceptable toxicity.

Biological: anti-CD20-CAR vector-transduced autologous T cells
anti-CD20-CAR vector-transduced autologous T cells
Other: genetically engineered lymphocyte therapy
genetically engineered lymphocyte therapy

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD20 vector (referred to as CART-20 cells).

II. Determine duration of in vivo survival of CART-20 cells. RT-PCR analysis of whole blood will be used to detect and quantify survival of CART-20 TCR zeta:4-1BB and TCR zeta cells over time.

SECONDARY OBJECTIVES:

I. For patients with detectable disease, measure anti-tumor response due to CART-20 cell infusions.

II. To determine if the 4-1BB transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of CART-20 TCR zeta:4-1BB and TCR zeta cells over time.

III. Estimate relative trafficking of CART-20 cells to tumor in bone marrow and lymph nodes.

IV. For patients with stored or accessible tumor cells (such as patients with active CLL, ALL, etc) determine tumor cell killing by CART-20 cells in vitro.

V. Determine if cellular or humoral host immunity develops against the murine anti-CD20, and assess correlation with loss of detectable CART-20 (loss of engraftment).

VI. Determine the relative subsets of CART-20 T cells (Tcm, Tem, and Treg).

OUTLINE: Patients are assigned to 1 of 2 groups according to order of enrollment.

Group 1 (Patients 1-5): Patients receive anti-CD20-CAR vector-transduced autologous T cells with 41BB-gamma vector on days 0,1, 2, and 11 in the absence of disease progression or unacceptable toxicity.

Group 2 (Patients 6-10): Patients receive anti-CD20-CAR vector-transduced autologous T cells with either 41BB-gamma vector or TCR zeta vector on days 0,1, 2, and 11 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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • •Male and female subjects with CD20+ 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

    • CD20+ leukemia or lymphoma
    • ALL in CR2 or CR3 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 CD20+:
    • 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 as initial therapy will be eligible.
    • Mantle cell lymphoma:
    • Beyond 1st CR 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 CD20+:
    • 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/AST < 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/CD28 costimulation
    • Any uncontrolled active medical disorder that would preclude participation as outlined
    • HIV infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01735604

Contacts
Contact: Han weidong, doctor +86-10-66937463 hanwdrsw@sina.com
Contact: Bo jian, doctor +86-10-13801257802 boj301@sina.com

Locations
China, Beijing
Biotherapeutic Department of Chinese PLA General Hospital Recruiting
Beijing, Beijing, China, 100853
Contact: Han weidong, Doctor    +86-10-66937463    hanwdrsw@sina.com   
Contact: Bo jian, Doctor    86-10-13801257802    boj301@sina.com   
Principal Investigator: Han weidong, Doctor         
Sub-Investigator: Bo Jian, Doctor         
Sub-Investigator: Wang Yao, Master         
Sponsors and Collaborators
Chinese PLA General Hospital
  More Information

No publications provided

Responsible Party: Han weidong, PI, Chinese PLA General Hospital
ClinicalTrials.gov Identifier: NCT01735604     History of Changes
Other Study ID Numbers: CHN-PLAGH-BT-001
Study First Received: November 23, 2012
Last Updated: March 2, 2013
Health Authority: China: Ethics Committee of Chinese PLA General Hospital

Additional relevant MeSH terms:
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
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoma, B-Cell
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 27, 2014