Treatment of Refractory/Relapsed Non-Hodgkin Lymphoma With CD19-TriCART Cell Therapy

NCT ID: NCT03720496

Last Updated: 2019-12-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-01
• Study Completion Date: 2021-12-01

Brief Summary

This is a single arm, open-label, phase Ⅰ study, to determine the safety and efficacy of CD19-TriCAR-T, an autologous tri-functional anti- CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in Refractory/ Relapsed CD19 Positive Non-Hodgkin Lymphoma (NHL).

Detailed Description

The tri-functional anti-CD19 chimeric antigen receptor contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the CD19-TriCAR-T to simultaneously targeting the CD19 positive NHL cells，blocking the inhibitory PD-L1 signal and stimulating T/NK cell activation and expansion.

Conditions

Non-hodgkin Lymphoma,B Cell

Keywords

CAR-T; TriCAR-T; CD19-TriCAR-T; Non-hodgkin Lymphoma; NHL; CD19-CAR-T

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CD19-TriCAR-T

Tri-functional anti-CD19 chimeric antigen receptor transduced autologous T cells will be administered intravenously

Group Type: EXPERIMENTAL

CD19-TriCAR-T

Intervention Type: BIOLOGICAL

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously at a target dose of 0.1-1 x 10\^6 CAR+ T cells/kg body weight.

Interventions

CD19-TriCAR-T

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously at a target dose of 0.1-1 x 10\^6 CAR+ T cells/kg body weight.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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. Histologically or cytologically confirmed CD19 positive non-Hodgkin lymphoma;

4. At least one measurable lesion per revised IWG Response Criteria;

5. Aged 18 to 69 years;

6. Expected survival ≥12 weeks;

7. Eastern cooperative oncology group (ECOG) performance status of ≤2;

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

9. All other treatment induced adverse events must have been resolved to

≤grade 1;

10. 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;

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 think the patient may not be suitable for the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Timmune Biotech Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Haifeng Lin

Role: PRINCIPAL_INVESTIGATOR

The Second Affiliated Hospital of Hainan Medical University

Locations

The Second Affiliated Hospital of Hainan Medical University

Haikou, Hainan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Haifeng Lin

Role: CONTACT

Phone: +86 13322060949

Email: 13322060949@163.com

Bin Gao, Dr.

Role: CONTACT

Phone: +86 022 59060560

Email: bin.gao@timmune.com

Facility Contacts

Haifeng Lin

Role: primary

Yasong Wu

Role: backup

References

Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. doi: 10.1016/j.ymthe.2016.10.020. Epub 2017 Jan 4.

Reference Type: BACKGROUND

PMID: 28129122 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28925994 (View on PubMed)

Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011 Aug 10;3(95):95ra73. doi: 10.1126/scitranslmed.3002842.

Reference Type: BACKGROUND

PMID: 21832238 (View on PubMed)

Other Identifiers

T2018-8

Identifier Type: -

Identifier Source: org_study_id