Clinical Trials /

Donor-derived Anti-CD123-CART Cells for Recurred AML After Allo-HSCT

NCT03114670

Description:

Patients with acute myeloid leukemia(AML) recurred after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a dismal prognosis.The investigators developed donor-derived chimeric antigen receptor modified-T cell(CART) to target CD123 for the treatment of AML. The investigators start the Phase I study aimed to treat recurred post-transplantation AML patients using donor-derived CAR-T. The purpose of this study is to assess the safety and effectiveness of anti-CD123 CAR-T cells in patients.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Unknown status

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Donor-derived Anti-CD123-CART Cells for Recurred AML After Allo-HSCT
  • Official Title: Donor-derived Anti-CD123 Chimeric Antigen Receptors Modified T Cells for Recurred Acute Myeloid Leukaemia After Allogeneic Hematopoietic Stem Cell Transplantation

Clinical Trial IDs

  • ORG STUDY ID: 307-RV-CAR-123
  • NCT ID: NCT03114670

Conditions

  • Adult Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
CD123CAR-41BB-CD3zeta-EGFRt-expressing T cellsanti-CD123 CART, CART123CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells

Purpose

Patients with acute myeloid leukemia(AML) recurred after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a dismal prognosis.The investigators developed donor-derived chimeric antigen receptor modified-T cell(CART) to target CD123 for the treatment of AML. The investigators start the Phase I study aimed to treat recurred post-transplantation AML patients using donor-derived CAR-T. The purpose of this study is to assess the safety and effectiveness of anti-CD123 CAR-T cells in patients.

Detailed Description

      Allo-HSCT is increasingly being used for AML, however, leukemia relapse remain a main problem
      for decades.Recently the investigators have witnessed great progresses in cancer therapy with
      chimeric antigen receptors modified T cells(CAR-T), especially for B-cell malignance.
      preclinical data about anti-CD123 CART have shown raised serious safety concerns of human
      anti-CD123 CAR-T for severe impairment of normal hematopoiesis in NSG mice.Patients with AML
      recurred after allo-HSCT have a dismal prognosis.The investigators developed donor-derived
      CART to target CD123 for the treatment of AML. The investigators start the Phase I study
      aimed to recurred post-transplantation AML patients using donor-derived CAR-T. The purpose of
      this study is to assess the safety and effectiveness of anti-CD123 CAR-T cells in patients.
    

Trial Arms

NameTypeDescriptionInterventions
CD123CAR-41BB-CD3zeta-EGFRt-expressing T cellsExperimentalPatients will receive a full dose CART infusion at day 0.
  • CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells

Eligibility Criteria

        Inclusion Criteria:

          1. Male and Female subjects with CD123+ acute myeloid leukemia as confirmed by
             immunohistochemistry and flow cytometry;

          2. Patients must have received an allogenic stem cell transplantation(Allo-HSCT). The
             leukemia relapsed. There are available donor or enough cryopreserved donor-derived
             PBMCs for CART preparation and subsequent Allo-HSCT. In the previous case, the donor
             should have adequate venous access for apheresis.

          3. Karnofsky score greater than 70%;

          4. patients more than 18 years of age

          5. Expected survival time >16 weeks;

          6. Bilirubin <3.0 mg/dL,

          7. Alanine aminotransferase(ALT)/ aspartate aminotransferase(AST)<3 fold normal.

          8. Diffusing capacity of the lung for carbon monoxide(DLCO) and forced expiratory volume
             in one second(FEV1)>45% of predictive value.

          9. At least received three kinds of medicines functioning by different mechanisms,
             including alkylating agents, protease inhibitors, and immunomodulators, and disease
             progressing within 60 days.

         10. Important organs are well tolerated;

         11. For post-transplantation patients, the apheresis would be undertaken only at least 2
             weeks after immunosuppressive agents for GvHD withdrawal;

         12. From very beginning of the test to 30 days after the withdrawal, men and women should
             adopt reliable contraceptive measures.

         13. All research participants must have the ability to understand and willingness to sign
             a written informed consent.

        Exclusion criteria:

          1. Patients were diagnosed with APL M3:t(15; 17)(q22; q12);PML/RARα );

          2. Symptomatic active central nervous system leukaemia;

          3. Patients with HIV, hepatitis B or C infection;

          4. Any concurrent active malignancies;

          5. Other uncontrolled active illness that hinders participation in the trial;

          6. Patients suffer from coronary heart disease, angina pectoris, myocardial infarction,
             arrhythmia, cerebral thrombosis, cerebral hemorrhage and other serious heart,
             cerebrovascular disease;

          7. patients with poorly controlled hypertensive

          8. patients with froward psychiatric history

          9. anyone who the researchers think unsuitable to participate in the investigation;

         10. anyone who long-term use of immunosuppressive agents for organ transplants or other
             reasons, or undertake inhaled corticosteroids therapy recently.

         11. failed production release testing: CAR+ T cells <30% or T cell expansion less than
             5-fold under the CD3/28 beads stimulation.

         12. Pregnant, lactating or female patients planning to get pregnant within 2 months before
             treatment ends;
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events related to treatment as assessed by NCI CTCAE version 4.03
Time Frame:15 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:CART cells persistence in vivo
Time Frame:15 years
Safety Issue:
Description:
Measure:CAR123-specific antibody level
Time Frame:15 years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:15 years
Safety Issue:
Description:
Measure:Disease response(CR, CRi)
Time Frame:15 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:Affiliated Hospital to Academy of Military Medical Sciences

Trial Keywords

  • Leukemia
  • Leukemia, Myeloid
  • Recurrence
  • Neoplasms by Histologic Type
  • Disease Attributes
  • Cyclophosphamide
  • Fludarabine
  • CD123
  • Chimeric Antigen Receptor modified T-cells

Last Updated

June 14, 2017