Investigator Initiated Phase 1 Study of TBI-1201

Plain-language summary

In this study, T lymphocytes engineered with a MAGE-A4-specific T-cell receptor (TCR) gene, called TBI-1201, are given to patients whose solid tumors express MAGE-A4. Patients first receive preparative treatment with cyclophosphamide and/or fludarabine. The Phase 1 trial enrolled patients with histologically or cytologically confirmed solid tumors that are unresectable, refractory to standard therapy, metastatic or recurrent, who are HLA-A*24:02 positive and whose tumors express MAGE-A4.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Completed

Sponsor

Mie University

Intervention

TBI-1201 (MAGE-A4-specific TCR gene transduced T lymphocytes), Cyclophosphamide (Endoxan), Fludarabine (Fludara)

Start date

4/1/2014

Estimated completion

3/1/2021

Countries

Japan

Related genes

Locations

• Tsu, Japan

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

1. Histologically or cytologically confirmed solid tumors
2. Solid tumor, which is unresectable , refractory to standard therapy (chemotherapy, radiotherapy, etc) , metastatic or recurrent
3. HLA-A\*24:02 positive
4. MAGE-A4-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/antibody, HBc antibody, or HCV antibody, and virus DNA observed in serum, except for HBs antibody positive case who had vaccine injection before.
6. Positive for antibodies against HIV or HTLV-1
7. Left Ventricular Ejection Fraction (LVEF): =\< 50％
8. Percutaneous Oxygen saturation: \< 94％
9. History of hypersensitivity reactions to bovine or murine derived substances.
10. History of hypersensitivity reaction to drugs used in this study
11. Psychological disorder or drug dependency which may have impact on the consent.
12. 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
13. 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.