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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02954445
Recruitment Status : Recruiting
First Posted : November 3, 2016
Last Update Posted : January 23, 2018
Information provided by (Responsible Party):
Zhi Yang, Southwest Hospital, China

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.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Multiple Myeloma Biological: Anti-BCMA-CAR-transduced T cells Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Research of BCMA-Targeted CAR-T in B Cell Malignancies
Study Start Date : October 2016
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: B Cell Malignancies
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.
Biological: Anti-BCMA-CAR-transduced T cells
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.
Other Name: BCMA-targeted CAR-T cells

Primary Outcome Measures :
  1. Adverse Events That Are Related to Treatment [ Time Frame: 3 years ]
    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 :
  1. In vivo existence of Anti-BCMA CAR-T cells [ Time Frame: 3 years ]
  2. Reaction Rate of Treatment [ Time Frame: 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02954445

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Contact: Cheng Qian, MD, PhD 0086-023-68765461
Contact: Shiqi Li, MD 0086-13206140093

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China, Chongqing
Southwest Hospital of Third Millitary Medical University Recruiting
Chongqing, Chongqing, China, 400000
Contact: Cheng Qian, PhD    008615086883400   
Contact: Zhi Yang, PhD    008613206140093   
Principal Investigator: Cheng Qian, PhD         
Sponsors and Collaborators
Southwest Hospital, China
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Principal Investigator: Cheng Qian, MD, PhD Biotherapy Center of Southwest Hospital

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Responsible Party: Zhi Yang, Principal Investigator of Biotherapy Center, Southwest Hospital, China Identifier: NCT02954445     History of Changes
Other Study ID Numbers: TMMU-BTC-009
First Posted: November 3, 2016    Key Record Dates
Last Update Posted: January 23, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Zhi Yang, Southwest Hospital, China:

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases