Treatment of Refractory/Relapsed Non-Hodgkin Lymphoma With TriCAR-T_CD19

NCT ID: NCT03497533

Last Updated: 2019-09-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-03
• Study Completion Date: 2020-12-31

Brief Summary

This is a single arm, open-label, single-center, phase 1/2 study, to determine the safety and efficacy of TriCAR-T-CD19, an autologous tri-functional anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in refractory/Relapsed 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 TriCAR-T-CD19 to simultaneously targeting the CD19 positive NHL，blocking the inhibitory PD-L1 signal and stimulating T/NK cell activation and expansion.

Conditions

Non-hodgkin Lymphoma,B Cell

Study Design

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

Study Groups

TriCAR-T-CD19

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

Group Type: EXPERIMENTAL

TriCAR-T-CD19

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 0.5-1 x 10\^6 CAR+ T cells/kg

Interventions

TriCAR-T-CD19

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 0.5-1 x 10\^6 CAR+ T cells/kg

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. Chemotherapy-refractory disease, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in the standard R-CHOP or CHOP chemotherapy; Disease progression or relapsed in ≤12 months of ASCT (must have biopsy proven recurrence in relapsed subjects); If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy.

5. No available standard therapy;

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

7. Aged 18 to 68 years;

8. Expected survival ≥12 weeks;

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

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

11. All other treatment induced adverse events must have been resolved to ≤grade 1;

12. 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);

13. Female must be not pregnant during the study.

Exclusion Criteria

1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years;

2. History of allogeneic stem cell transplantation;

3. Prior other CAR therapy or other genetically modified T cell therapy;

4. 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;

5. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases;

6. Lactating women;

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

8. Subjects need systematic usage of corticosteroid;

9. History of any gene therapy;

10. Subjects need systematic usage of immunosuppressive drug;

11. Known history of infection with HIV;

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

13. Other reasons the investigator think the patient may not be suitable for the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 68 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hunan Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Timmune Biotech Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ming Zhou

Role: PRINCIPAL_INVESTIGATOR

Hunan Provincial People's Hospital

Locations

Hunan Provincial People's Hospital

Changsha, Hunan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ming Zhou

Role: CONTACT

zhouming_0321@163.com

+86 0731 83928147

Bin Gao

Role: CONTACT

bin.gao@timmune.com

+86 022 59060560 ext. 803

Facility Contacts

Jianjun Chen

Role: primary

+86 0731 83928147

Ming Zhou

Role: backup

zhouming_0321@163.com

+86 0731 83928145

References

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)

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: RESULT

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: RESULT

PMID: 28925994 (View on PubMed)

Other Identifiers

ChiCTR1800014528

Identifier Type: -

Identifier Source: org_study_id