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A Clinical Research of BCMA-Targeted CAR-T in B Cell Malignancies

Primary Purpose

Leukemia, Lymphoma, Multiple Myeloma

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Anti-BCMA-CAR-transduced T cells
Sponsored by
Southwest Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring BCMA, CAR-T

Eligibility Criteria

14 Years - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. BCMA-expressing B cell malignancy must be assured and must be relapsed or refractory disease. According to current traditional therapies, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time.
  2. Patients enrolled must have an evaluated score above 60 with KPS.
  3. BCMA expression of the malignant cells must be detected by immunohistochemistry or by flow cytometry. In general immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples.
  4. Gender is not limited, age from 14 years to 75 years.
  5. Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
  6. Patients are expected to survive for more than 3 months by their physicians at the time of enrollment.
  7. Adequate absolute CD3 count estimated need to be assured for obtaining target cell dose based on dosage cohorts.
  8. Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:

    CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs; CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm CNS3 with marrow disease who has failed salvage systemic and intensive IT chemotherapy (and therefore not eligible for radiation)

  9. Ability to give informed consent.
  10. Cardiac function: Left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO.
  11. Renal function: Creatinine level of peripheral blood is required no greater than 133umol/L.
  12. Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
  13. Patients with history of allogeneic stem cell transplantation are eligible if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
  14. Patients volunteer to participate in the research.

Exclusion Criteria:

  1. Evident signs suggesting that patients are potentially allergic to cytokines.
  2. Frequent infection history and recent infection is uncontrolled.
  3. Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
  4. Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
  5. Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications.
  6. Pregnancy and nursing females.
  7. HIV infection.
  8. Active hepatitis B or active hepatitis C.
  9. Participation in a prior investigational study within 4 weeks prior to enrollment or longer if required by local regulation. Participation in non-therapeutic research studies is allowed.
  10. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
  11. Patients with a known history or prior diagnosis of other serious immunologic, malignant or inflammatory disease.
  12. Other situations we think not eligible for participation in the research.

Sites / Locations

  • Southwest Hospital of Third Millitary Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

B Cell Malignancies

Arm Description

The trial will be conducted in a manner of simon two-stage design with Anti-BCMA-CAR-transduced T cells, beginning in the first stage with the aim of over 30% reaction rate among 15 patients with B cell malignancies. Only when the expected reaction rate is achieved the 30 patients left can be recruited.

Outcomes

Primary Outcome Measures

Adverse Events That Are Related to Treatment
Determine the toxicity profile of the BCMA targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

Secondary Outcome Measures

In vivo existence of Anti-BCMA CAR-T cells
Reaction Rate of Treatment

Full Information

First Posted
November 2, 2016
Last Updated
June 23, 2019
Sponsor
Southwest Hospital, China
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1. Study Identification

Unique Protocol Identification Number
NCT02954445
Brief Title
A Clinical Research of BCMA-Targeted CAR-T in B Cell Malignancies
Official Title
A Clinical Research of BCMA-Targeted CAR-T in B Cell Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Unknown status
Study Start Date
October 2016 (undefined)
Primary Completion Date
October 2019 (Anticipated)
Study Completion Date
October 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Southwest Hospital, China

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The overall purpose of this study is to explore the therapeutic effect of BCMA-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of B-cell derived malignancies.
Detailed Description
B-cell maturation antigen(BCMA) is preferentially expressed in mature B lymphocytes as well as in B-cell derived leukemia, lymphomas, and multiple myeloma. Despite of the fact that CD19-targeted CAR-T can re-induce remissions for many patients with relapsed and refractory B cell malignancies, a part of those patients will relapse with CD19-negative malignancies. To explore a rescue for those with CD19-negative B cell malignancies, this trial is designed and conducted to test the safety and effect of BCMA-targeted CAR-T.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma, Multiple Myeloma
Keywords
BCMA, CAR-T

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
45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
B Cell Malignancies
Arm Type
Experimental
Arm Description
The trial will be conducted in a manner of simon two-stage design with Anti-BCMA-CAR-transduced T cells, beginning in the first stage with the aim of over 30% reaction rate among 15 patients with B cell malignancies. Only when the expected reaction rate is achieved the 30 patients left can be recruited.
Intervention Type
Biological
Intervention Name(s)
Anti-BCMA-CAR-transduced T cells
Other Intervention Name(s)
BCMA-targeted CAR-T cells
Intervention Description
The first 3 enrolled patients will receive autologous-derived BCMA-targeted CAR-T cells on day 1, 2 and 3 with respective 10%, 30% and 60% of the total expected dosage after receiving lymphodepleting chemotherapy. If the 3 patients don't display severe toxicity, the next patients enrolled will get infused in 2 days with respective 40% and 60% total dosage.
Primary Outcome Measure Information:
Title
Adverse Events That Are Related to Treatment
Description
Determine the toxicity profile of the BCMA targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
In vivo existence of Anti-BCMA CAR-T cells
Time Frame
3 years
Title
Reaction Rate of Treatment
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: BCMA-expressing B cell malignancy must be assured and must be relapsed or refractory disease. According to current traditional therapies, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time. Patients enrolled must have an evaluated score above 60 with KPS. BCMA expression of the malignant cells must be detected by immunohistochemistry or by flow cytometry. In general immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples. Gender is not limited, age from 14 years to 75 years. Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis. Patients are expected to survive for more than 3 months by their physicians at the time of enrollment. Adequate absolute CD3 count estimated need to be assured for obtaining target cell dose based on dosage cohorts. Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy: CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs; CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm CNS3 with marrow disease who has failed salvage systemic and intensive IT chemotherapy (and therefore not eligible for radiation) Ability to give informed consent. Cardiac function: Left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO. Renal function: Creatinine level of peripheral blood is required no greater than 133umol/L. Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus. Patients with history of allogeneic stem cell transplantation are eligible if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to enrollment. Patients volunteer to participate in the research. Exclusion Criteria: Evident signs suggesting that patients are potentially allergic to cytokines. Frequent infection history and recent infection is uncontrolled. Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment. Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications. Pregnancy and nursing females. HIV infection. Active hepatitis B or active hepatitis C. Participation in a prior investigational study within 4 weeks prior to enrollment or longer if required by local regulation. Participation in non-therapeutic research studies is allowed. Class III/IV cardiovascular disability according to the New York Heart Association Classification. Patients with a known history or prior diagnosis of other serious immunologic, malignant or inflammatory disease. Other situations we think not eligible for participation in the research.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cheng Qian, MD, PhD
Phone
0086-023-68765461
Email
cqian3184@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Shiqi Li, MD
Phone
0086-13206140093
Email
yz2003can@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cheng Qian, MD, PhD
Organizational Affiliation
Biotherapy Center of Southwest Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southwest Hospital of Third Millitary Medical University
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheng Qian, PhD
Phone
008615086883400
Email
cqian3184@163.com
First Name & Middle Initial & Last Name & Degree
Zhi Yang, PhD
Phone
008613206140093
Email
yz2003can@126.com
First Name & Middle Initial & Last Name & Degree
Cheng Qian, PhD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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A Clinical Research of BCMA-Targeted CAR-T in B Cell Malignancies

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