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Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by Tandem CAR T Cells Targeting CD19 and CD22

Primary Purpose

Hematopoietic/Lymphoid Cancer, Adult Acute Lymphoblastic Leukemia in Remission, B-cell Adult Acute Lymphoblastic Leukemia

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
anti-CD19/22-CAR vector-transduced T cells
Sponsored by
Chinese PLA General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematopoietic/Lymphoid Cancer

Eligibility Criteria

5 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male and female subjects with CD19/22+ 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 CD19/22+ 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 CD19/22+:

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

Sites / Locations

  • Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

anti-CD19/22 CAR T cells

Arm Description

Patients receive anti-CD19/22-CAR retroviral vector-transduced autologous or donor-derived T cells on days 0,1, 2 in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Anti-tumor responses to tanCART19/22 cell infusions

Full Information

First Posted
June 10, 2017
Last Updated
April 16, 2019
Sponsor
Chinese PLA General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03185494
Brief Title
Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by Tandem CAR T Cells Targeting CD19 and CD22
Official Title
Clinical Study of CD19/CD22 Tan CAR T Cells in Relapsed and/or Chemotherapy Refractory B-cell Leukemias and Lymphomas
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Unknown status
Study Start Date
August 1, 2017 (Actual)
Primary Completion Date
August 1, 2019 (Anticipated)
Study Completion Date
August 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese PLA General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19/CD22 vector (referred to as tanCART-19/22 cells). II. Determine duration of in vivo survival of tanCART-19/22 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of tanCART-19/22TCR (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 tanCART-19/22 cell infusions. II. CD137 transgene is measured by the relative engraftment levels of tanCART-19/22 CD137 and TCR zeta cells over time. III. Estimate relative trafficking of tanCART-19/22 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 tanCART-19/22 cells in vitro. V. Determine if cellular or humoral host immunity develops against the murine anti-CD19/22, and assess correlation with loss of detectable tanCART-19/20 (loss of engraftment). VI. Determine the relative subsets of tanCART-19/22 T cells (Tcm, Tem, and Treg). OUTLINE: Patients are assigned to 1 group according to order of enrollment. Patients receive anti-CD19/22-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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic/Lymphoid Cancer, Adult Acute Lymphoblastic Leukemia in Remission, B-cell Adult Acute Lymphoblastic Leukemia, B-Cell Chronic Lymphocytic Leukemia in Relapse (Diagnosis), 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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
anti-CD19/22 CAR T cells
Arm Type
Experimental
Arm Description
Patients receive anti-CD19/22-CAR retroviral vector-transduced autologous or donor-derived T cells on days 0,1, 2 in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
anti-CD19/22-CAR vector-transduced T cells
Other Intervention Name(s)
genetically engineered lymphocyte therapy
Intervention Description
genetically engineered lymphocyte therapy
Primary Outcome Measure Information:
Title
Occurrence of study related adverse events
Description
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
Time Frame
Until week 24
Secondary Outcome Measure Information:
Title
Anti-tumor responses to tanCART19/22 cell infusions
Time Frame
up to 24 weeks
Other Pre-specified Outcome Measures:
Title
in vivo existence of tanCART19/22
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female subjects with CD19/22+ 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 CD19/22+ 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 CD19/22+: 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
Facility Information:
Facility Name
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100853
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
32245502
Citation
Dai H, Wu Z, Jia H, Tong C, Guo Y, Ti D, Han X, Liu Y, Zhang W, Wang C, Zhang Y, Chen M, Yang Q, Wang Y, Han W. Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia. J Hematol Oncol. 2020 Apr 3;13(1):30. doi: 10.1186/s13045-020-00856-8. Erratum In: J Hematol Oncol. 2020 May 18;13(1):53.
Results Reference
derived

Learn more about this trial

Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by Tandem CAR T Cells Targeting CD19 and CD22

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