Clinical trial NCT03497533: Treatment of Refractory/Relapsed Non-Hodgkin Lymphoma With TriCAR-T_CD19
Official title: TriCAR-T-CD19 Adoptive Immunotherapy for CD19-positive Refractory/Relapsed Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Non-hodgkin Lymphoma,B Cell
Keywords: CD19
CAR-T
TriCAR-T-CD19
non-Hodgkin lymphoma
NHL
Lead sponsor: Timmune Biotech Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hunan Provincial People's Hospital
First posted: 2018-04-13
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.0)
timeFrame: 30 Days
Secondary outcomes:
measure: Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
timeFrame: 12 months
measure: Partial response rate [PR] (Partial response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
timeFrame: 12 months
measure: Duration of Response （The time from response to relapse or progression）
timeFrame: 12 months
measure: Progression Free Survival（The time from the first day of treatment to the date on which disease progresses.）
timeFrame: 12 months
measure: Overall Survival（The number of patient alive, with or without signs of cancer）
timeFrame: 24 months
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
Study officials:
affiliation: Hunan Provincial People's Hospital
name: Ming Zhou
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.