Investigator Initiated Phase 1 Study of TBI-1201

Solid Tumors Clinical Trial

Official title:

Multi-center, Investigator Initiated Phase 1 Study of MAGE-A4 Specific TCR Gene Transferred T Lymphocytes With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02096614
• Other study ID #: 1201-01
• Status: Completed
• Phase: Phase 1
• Start date: April 2014
• Est. completion date: March 2021

Study information

• Verified date: June 2021
• Source: Mie University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: March 2021
• Est. primary completion date: March 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

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.

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• TBI-1201
TBI-1201(5*10^8 or 5*10^9) is administered.
• Cyclophosphamide
Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1201
• Fludarabine
Fludarabine (20mg/m2 x 5 days Intravenous(IV)) is administered as pre-treatment medication of TBI-1201 in combination with cyclophosphamide.

Locations

Country	Name	City	State
Japan	Mie University Hospital	Tsu	Mie

Sponsors (5)

Lead Sponsor	Collaborator
Mie University	Fiverings Co., Ltd., Shionogi, Statcom Co. Ltd., Takara Bio Inc.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and grade of adverse events (CTCAE)	Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.	8 weeks
Primary	Appearance of replication competent retrovirus by PCR	Confirm no replication competent retrovirus observed	8 weeks
Primary	Appearance of clonality by LAM-PCR	Confirm no clonality is observed	8 weeks
Primary	Kinetics of TBI-1201 in blood by realtime-PCR and flow cytometry	Evaluate persistence and expansion of transferred TBI-1201	8 weeks