Clinical Trials /

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

NCT02954445

Description:

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.

Related Conditions:
  • B-Cell Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: TMMU-BTC-009
  • NCT ID: NCT02954445

Conditions

  • Leukemia
  • Lymphoma
  • Multiple Myeloma

Interventions

DrugSynonymsArms
Anti-BCMA-CAR-transduced T cellsBCMA-targeted CAR-T cellsB Cell Malignancies

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
B Cell MalignanciesExperimentalThe 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.
  • Anti-BCMA-CAR-transduced T cells

Eligibility Criteria

        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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:14 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events That Are Related to Treatment
Time Frame:3 years
Safety Issue:
Description: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

Measure:In vivo existence of Anti-BCMA CAR-T cells
Time Frame:3 years
Safety Issue:
Description:
Measure:Reaction Rate of Treatment
Time Frame:3 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southwest Hospital, China

Trial Keywords

  • BCMA
  • CAR-T

Last Updated

June 23, 2019