Clinical Trials /

A Clinical Research of CD123-Targeted CAR-T in Myeloid Malignancies

NCT02937103

Description:

The overall purpose of this study is to explore the therapeutic effect of CD123-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of Myeloid Malignancies.

Related Conditions:
  • Myeloid Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Clinical Research of CD123-Targeted CAR-T in Myeloid Malignancies
  • Official Title: A Clinical Research of CD123-Targeted CAR-T in Myeloid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: TMMU-BTC-008
  • NCT ID: NCT02937103

Conditions

  • Leukemia

Interventions

DrugSynonymsArms
Anti-CD123-CAR-transduced T cellsCD123-targeted CAR-T cellsMyeloid Malignancies

Purpose

The overall purpose of this study is to explore the therapeutic effect of CD123-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of Myeloid Malignancies.

Detailed Description

      Great progress has been made in the treatment of relapsed and refractory B cell malignancies
      with CD19-targeted CAR-T cells. However, for myeloid malignancies, which has higher
      morbidity, trials of CAR-T is few. CD123 is expressed on most myeloid leukemia cells so it is
      a ideal target for CAR-T. Some researches have revealed that CD123 is a marker of leukemia
      stem cells, which indicates that the eradication of CD123+ cells may prevent relapse of
      leukemia. This trial is designed and conducted to test the safety and effectiveness of
      CD123-targeted CAR-T.
    

Trial Arms

NameTypeDescriptionInterventions
Myeloid MalignanciesExperimentalThe trial will be conducted in a manner of simon two-stage design with Anti-CD123-CAR-transduced T cells, beginning in the first stage with the aim of over 30% reaction rate among 15 patients with myeloid malignancies. Only when the expected reaction rate is achieved the 30 patients left can be recruited.
  • Anti-CD123-CAR-transduced T cells

Eligibility Criteria

        Inclusion Criteria:

          1. CD123-expressing myeloid 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. CD123 expression of the malignant cells must be detected by immunohistochemistry or by
             flow cytometry.

          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:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Adverse Events That Are Related to Treatment
Time Frame:3 years
Safety Issue:
Description:Determine the toxicity profile of the CD123 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

Secondary Outcome Measures

Measure:In vivo existence of Anti-CD123 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

  • Leukemia
  • Myeloid
  • CD123
  • CAR-T

Last Updated

June 23, 2019