Description:
Following pre-treatment with cyclophosphamide and/or fludarabine, MAGE-A4-specific TCR gene transduced T lymphocytes are transferred to the patients with MAGE-A4-expressing solid tumors.
Clinical Trials /
Investigator Initiated Phase 1 Study of TBI-1201
NCT02096614
Related Conditions:
- Malignant Solid Tumor
Recruiting Status:
Completed
Phase:
Phase 1
Trial Eligibility
Document
Title
- Brief Title: Investigator Initiated Phase 1 Study of TBI-1201
- Official Title: Multi-center, Investigator Initiated Phase 1 Study of MAGE-A4 Specific TCR Gene Transferred T Lymphocytes With Solid Tumors
Clinical Trial IDs
- ORG STUDY ID: 1201-01
- NCT ID: NCT02096614
Conditions
- Solid Tumors
Interventions
| Drug | Synonyms | Arms |
|---|---|---|
| TBI-1201 | MAGE-A4-specific TCR gene transduced T lymphocytes | High dose TBI-1201 with pre-treatment 1 |
| Cyclophosphamide | Endoxan | High dose TBI-1201 with pre-treatment 1 |
| Fludarabine | Fludara | High dose TBI-1201 with pre-treatment 2 |
Purpose
Following pre-treatment with cyclophosphamide and/or fludarabine, MAGE-A4-specific TCR gene
transduced T lymphocytes are transferred to the patients with MAGE-A4-expressing solid
tumors.
Detailed Description
Following pre-treatment with cyclophosphamide alone or in combination with fludarabine,
MAGE-A4-specific TCR gene transduced T lymphocytes are transferred to HLA-A*24:02 positive
patients with solid tumors which are 1) unresectable, refractory to standard therapy
(chemotherapy, radiotherapy, etc), metastatic or recurrent, and 2) MAGE-A4-expressing. The
primary objective is to evaluate the safety and in vivo kinetics, and the secondary is to
evaluate clinical effect.
Trial Arms
| Name | Type | Description | Interventions |
|---|---|---|---|
| Low dose TBI-1201 with pre-treatment 1 | Experimental | TBI-1201(5*10^8) single-dose administration with pre-treatment of cyclophosphamide alone. |
|
| High dose TBI-1201 with pre-treatment 1 | Experimental | TBI-1201(5*10^9) single-dose administration with pre-treatment of cyclophosphamide alone. |
|
| High dose TBI-1201 with pre-treatment 2 | Experimental | TBI-1201(5*10^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine. |
|
| TBI-1201 with pre-treatment 1 or 2 | Experimental | Arm1, 2 or 3, which is considered as optimal. |
|
Eligibility Criteria
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.
| 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: | 8 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: | Completed |
| Lead Sponsor: | Mie University |
Trial Keywords
- Adoptive cell transfer
- Cell therapy
- Immunotherapy
- MAGE-A4
- Esophageal cancer
- Melanoma
- Head and neck cancer
- Ovarian cancer
- TCR gene therapy
Last Updated
June 18, 2021
