Clinical Trials /

Investigator Initiated Phase 1 Study of TBI-1301

NCT02366546

Description:

Following pre-treatment with cyclophosphamide and/or fludarabine, NY-ESO-1-specific TCR gene transduced T lymphocytes are transferred to the patients with NY-ESO-1-expressing solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Investigator Initiated Phase 1 Study of TBI-1301
  • Official Title: Multi-center, Investigator Initiated Phase 1 Study of NY-ESO-1 Specific TCR Gene Transferred T Lymphocytes With Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 1301-01
  • NCT ID: NCT02366546

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
TBI-1301NY-ESO-1-specific TCR gene transduced T lymphocytesLow dose TBI-1301 with pre-treatment 1
CyclophosphamideEndoxanLow dose TBI-1301 with pre-treatment 1
FludarabineFludaraHigh dose TBI-1301 with pre-treatment 2

Purpose

Following pre-treatment with cyclophosphamide and/or fludarabine, NY-ESO-1-specific TCR gene transduced T lymphocytes are transferred to the patients with NY-ESO-1-expressing solid tumors.

Detailed Description

      Following pre-treatment with cyclophosphamide alone or in combination with fludarabine,
      NY-ESO-1-specific TCR gene transduced T lymphocytes are transferred to HLA-A*02:01 or
      HLA-A*02:06 positive patients with solid tumors which are 1) unresectable, refractory to
      standard therapy (chemotherapy, radiotherapy, etc), and 2) NY-ESO-1-expressing. The primary
      objective is to evaluate the safety and in vivo kinetics, and the secondary is to evaluate
      clinical effect.
    

Trial Arms

NameTypeDescriptionInterventions
Low dose TBI-1301 with pre-treatment 1ExperimentalTBI-1301(5*10^8) single-dose administration with pre-treatment of cyclophosphamide alone.
  • TBI-1301
  • Cyclophosphamide
High dose TBI-1301 with pre-treatment 1ExperimentalTBI-1301(5*10^9) single-dose administration with pre-treatment of cyclophosphamide alone.
  • TBI-1301
  • Cyclophosphamide
High dose TBI-1301 with pre-treatment 2ExperimentalTBI-1301(5*10^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.
  • TBI-1301
  • Cyclophosphamide
  • Fludarabine
TBI-1301 with pre-treatment 1 or 2ExperimentalArm1, 2 or 3, which is considered as optimal.
  • TBI-1301
  • Cyclophosphamide
  • Fludarabine

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed solid tumors

          2. Solid tumor, which is unresectable, refractory to standard therapy (chemotherapy,
             radiotherapy, etc)

          3. HLA-A*02:01 or HLA-A*02:06 positive

          4. NY-ESO-1-expression by PCR or immunohistochemistry

          5. ECOG Performance Status, 0 or 1

          6. Age >=20 years on consent

          7. No treatment (surgery, chemotherapy, radiotherapy, etc.) and expected sufficient
             recovery from the treatment at the time of the lymphocytes collection for gene
             transfer.

          8. Life expectancy >=16 weeks after consent

          9. No severe damage on the major organs (bone marrow, heart, lung, liver, kidney, etc)
             and meet the following lab value criteria:

               -  WBC >= 2,500/μL

               -  Hemoglobin >= 8.0g/dL

               -  Platelets >= 75,000/μL

               -  T. bilirubin < 1.5 x ULN

               -  AST(GOT), ALT(GPT) < 3.0 x ULN

               -  Creatinine < 1.5 x ULN

         10. Ability to understand the study contents and to give a written consent at his/her free
             will.

        Exclusion Criteria:

          1. The following serious complications are excluded from the study;

               -  Unstable angina, cardiac infarction, or heart failure

               -  Uncontrolled diabetes or hypertension

               -  Active infection

               -  Obvious interstitial pneumonia or lung fibrosis by chest X-ray

               -  Active autoimmune disease requiring steroids or immunosuppressive therapy.

          2. Serious hypersensitivity

          3. Tumor cell invasion into CNS

          4. Active multiple cancer

          5. Positive for HBs antigen or HBV-DNA observed in serum

          6. Positive for HCV antibody and HCV-RNA observed in serum

          7. Positive for antibodies against HIV or HTLV-1

          8. Left Ventricular Ejection Fraction (LVEF): <= 50%

          9. Percutaneous Oxygen saturation: < 94%

         10. History of serious hypersensitivity reactions to bovine or murine derived substances.

         11. History of hypersensitivity reaction to drugs used in this study.

         12. Psychological disorder or drug dependency which may have impact on the consent.

         13. Pregnant females, lactating females (except when they cease and don't resume
             lactation) or female and male patients who cannot agree to practice the adequate birth
             control after the consent during the study

         14. Clinically significant systemic illness that in the judgment of the PI or
             sub-investigator would compromise the patient's ability to tolerate protocol therapy
             or significantly increase the risk of complications.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and grade of adverse events (CTCAE)
Time Frame:4 weeks
Safety Issue:
Description:• Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mie University

Trial Keywords

  • Adoptive cell transfer
  • Cell therapy
  • Immunotherapy
  • NY-ESO-1
  • Esophageal cancer
  • Melanoma
  • Head and neck cancer
  • Ovarian cancer
  • Synovial sarcoma
  • TCR gene therapy

Last Updated