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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03649529
Other study ID # T2018-7
Secondary ID
Status Recruiting
Phase Early Phase 1
First received
Last updated
Start date September 27, 2018
Est. completion date January 1, 2022

Study information

Verified date December 2019
Source Timmune Biotech Inc.
Contact Haifeng Lin
Phone +86 13322060949
Email 13322060949@163.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Malignant melanoma have been reported to be characterized with high gp100 expression. Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells. When infused back to the patient, the GPA-TriMAR-T cells will recognize and kill target cells that express gp100(209-217) peptides in the form MHC-I complex, thus eliminating malignant melanoma from the body.


Description:

GPA-TriMAR is a modified chimeric antigen receptor (CAR) that consist of three subunit in it's outer membrane domain. The outer membrane domain linked to the inner membrane 4-1BB/CD3ΞΆ domain through the transmembrane domain, thus compose the complete chimeric antigen receptor. Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells. When infused back to the patient, the modified GPA-TriMAR-T cells will recognize and kill malignant melanoma cells in the body, and in the meanwhile the other two subunits function to stimulate the innate immune system and enhance GPA-TriMAR-T cells tumor Infiltration.


Recruitment information / eligibility

Status Recruiting
Enrollment 6
Est. completion date January 1, 2022
Est. primary completion date September 15, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years to 69 Years
Eligibility Inclusion Criteria:

1. All subjects must personally sign and date the consent form before initiating any study specific procedures or activities;

2. All subjects must be able to comply with all the scheduled procedures in the study;

3. HLA_A2 genotype and gp100 positive malignant melanoma: ? stage or relapsed after surgery or chemotherapy or no available standard therapy;

4. At least one measurable lesion per RECIST V1.1;

5. Aged 18 to 69 years;

6. Expected survival =12 weeks; Eastern cooperative oncology group (ECOG) performance status of=2;

7. Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks;

8. All other treatment induced adverse events must have been resolved to =grade 1;

9. Laboratory tests must fulfill the following criteria: ANC = 1000/uL, HGB>70g/L, Platelet count = 50,000/uL, Creatinine clearance =1.5 ULN, Serum ALT/AST =2.5 ULN, Total bilirubin =1.5 ULN (except in subjects with Gilbert's syndrome);

Exclusion Criteria:

1. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring iv antimicrobials for management. (Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment);

2. Patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. Symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. The specific selection is ultimately determined by the investigator;

3. Lactating women or women of childbearing age who plan to conceive during the time period;

4. Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive);

5. Known history of infection with HIV;

6. Subjects need systematic usage of corticosteroid;

7. Subjects need systematic usage of immunosuppressive drug;

8. Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study;

9. Other reasons the investigator consider the patient may not be suitable for the study.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
GPA-TriMAR-T
Patients will undergo leukapheresis to isolate autologous T cells, these T cells will be activated and modified to express GPA-TriMAR in the manufacture facility, and eventually infused back into the body for treatment.

Locations

Country Name City State
China Hainan Cancer Hospital Haikou Hainan
China The Second Affiliated Hospital of Hainan Medical University Haikou Hainan

Sponsors (3)

Lead Sponsor Collaborator
Timmune Biotech Inc. Hainan Cancer Hospital, The Second Affiliated Hospital of Hainan Medical University

Country where clinical trial is conducted

China, 

References & Publications (3)

Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19. Review. — View Citation

Zhang G, Liu R, Zhu X, Wang L, Ma J, Han H, Wang X, Zhang G, He W, Wang W, Liu C, Li S, Sun M, Gao B. Retargeting NK-92 for anti-melanoma activity by a TCR-like single-domain antibody. Immunol Cell Biol. 2013 Nov-Dec;91(10):615-24. doi: 10.1038/icb.2013.45. Epub 2013 Oct 8. — View Citation

Zhang G, Wang L, Cui H, Wang X, Zhang G, Ma J, Han H, He W, Wang W, Zhao Y, Liu C, Sun M, Gao B. Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor. Sci Rep. 2014 Jan 6;4:3571. doi: 10.1038/srep03571. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.03) Incidence of treatment-related adverse events as assessed by CTCAE v4.03 24 months
Secondary Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria) Complete response rate per the revised International Working Group (IWG) Response Criteria 24 months
Secondary Partial response rate [PR] (Partial response rate per the revised International Working Group (IWG) Response Criteria) Partial response rate per the revised International Working Group (IWG) Response Criteria 24 months
Secondary Duration of Response (The time from response to relapse or progression) The time from response to relapse or progression 24 months
Secondary Progression Free Survival (The time from the first day of treatment to the date on which disease progresses.) The time from the first day of treatment to the date on which disease progresses. 24 months
Secondary Overall Survival (The number of patient alive, with or without signs of cancer) The number of patient alive, with or without signs of cancer 24 months
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