Clinical Trials /

Study of TBI-1501 for Relapsed or Refractory Acute Lymphoblastic Leukemia

NCT03155191

Description:

Evaluate the safety (P-I), pharmacokinetics and anti-tumor effect of immunotherapy of autologous T cells genetically modified to express anti-CD19 chimeric antigen receptor (CAR) (TBI-1501) for relapsed or refractory CD19+ B-cell acute lymphoblastic leukemia.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of TBI-1501 for Relapsed or Refractory Acute Lymphoblastic Leukemia
  • Official Title: A Multicenter Phase I/II Study for Relapsed or Refractory CD19+ B-acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 1501-01
  • NCT ID: NCT03155191

Conditions

  • Lymphoblastic Leukemia, Acute Adult

Interventions

DrugSynonymsArms
TBI-1501Dose Level -1 to 2

Purpose

Evaluate the safety (P-I), pharmacokinetics and anti-tumor effect of immunotherapy of autologous T cells genetically modified to express anti-CD19 chimeric antigen receptor (CAR) (TBI-1501) for relapsed or refractory CD19+ B-cell acute lymphoblastic leukemia.

Detailed Description

      Enroll patients after confirming eligibility. Following enrollment, peripheral blood
      mononuclear cells and blood plasma will be obtained from each subject by apheresis to start
      the manufacturing of TBI-1501.

      Before TBI-1501 administration, it is necessary to pass the quality tests. Subject will be
      hospitalized from Day -3 to Day 28, and administered Cyclophosphamide (1,000 mg/m2/day×2
      days) on Day -3 and Day -2.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Level -1 to 2Experimental0.3 to 3 x 10^6 autologous CD19-CAR-T cells/kg per patient will be administered intravenously after a conditioning chemotherapy with cyclophosphamide. cohort -1: 3×10^5 cells/kg cohort 1: 1×10^6 cells/kg cohort 2: 3×10^6 cells/kg.
  • TBI-1501

Eligibility Criteria

        Inclusion Criteria:

          1. In phase-1 study, patients must be ≥ 18 years of age. In phase-2 study, patients must
             be ≥ 16 years of age.

          2. Patients with relapse or refractory CD19+ acute B-cell lymphoblastic leukemia

          3. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0, 1 or 2.

          4. Patients must have adequate key organ function (bone marrow, heart, lung, liver,
             renal, etc), as defined below

               -  Total bilirubin level ≤1.5xULN (Upper limit of normal)

               -  AST(GOT)/ALT(GPT) level ≤5.0xULN

               -  Serum creatinine ≤2.0mg/dL

               -  SpO2 ≧ 92%

               -  LVEF ≥50%

          5. Patients must be able to understand and willing to sign a written informed consent
             document (for patients <20 years of age their legal guardian must give informed
             consent).

        Exclusion Criteria:

          1. White blood cell counts ≧ 50,000/uL

          2. Received expected antitumor therapy (chemotherapy or radiation therapy, etc) within 2
             weeks.

          3. Received HSCT within 12 weeks before enrollment.

          4. Under treatment for GVHD.

          5. lymphocytes except for blasts ≦ 500/uL

          6. Presence of active CNS-3

          7. Concurrent use of systemic steroids or immunosuppressive agents (except for
             replacement therapy and local administration. e.g. inhalation, application and so on).

          8. HBs Ag positive ,or either HBc Ab positive or HBs positive with HBV-DNA > 1.3LogIU/ml

          9. Presence of active hepatitis C infection

         10. HIV Ab or anti-HTLV-1 Ab positive

         11. History of allergy about component of investigational product or animal(cattle and/or
             mouse)-derived additives

         12. Hypersensitivity to antibiotics.

         13. Presence of symptomatic cardiac arrhythmias or serious heart disease.

         14. Presence of another malignant tumor.

         15. Psychiatric disorder, alcohol addiction or drug addiction that affects the ability of
             informed consent.

         16. Active or serious infection.

         17. Both men and women who have generative functions, and who cannot agree with using
             contraceptive devices from the day of the consent to the end of study.

         18. Pregnant or lactating women.

         19. Any other patients judged by the investigators to be inappropriate for the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase-I portion: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:One year
Safety Issue:
Description:Adverse event (frequency, seriousness, duration, causality, severity, classification), mortality, severe adverse event, discontinuation due to adverse event.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Takara Bio Inc.

Trial Keywords

  • Acute lymphoblastic leukemia
  • Leukemia
  • Lymphoblastic
  • TBI-1501
  • Anti-CD19 CAR Expressing T cells Therapy
  • CD19 CAR Gene-Transduced Lymphocyte
  • Adoptive Immunotherapy
  • Genetically Engineered Lymphocyte Therapy
  • Retroviral Vector
  • Neoplasms by Histologic Type
  • Neoplasms
  • Neoplasms, Experimental
  • Immune System Diseases
  • Chimeric antigen receptor

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