Clinical trial NCT03720496: Treatment of Refractory/Relapsed Non-Hodgkin Lymphoma With CD19-TriCART Cell Therapy
Official title: Adoptive Immunotherapy for Refractory/Relapsed Non-Hodgkin Lymphoma With CD19-TriCART Cells
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Non-hodgkin Lymphoma,B Cell
Keywords: CAR-T
TriCAR-T
CD19-TriCAR-T
Non-hodgkin Lymphoma
NHL
CD19-CAR-T
Lead sponsor: Timmune Biotech Inc.
Sponsor class: INDUSTRY
First posted: 2018-10-25
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
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, 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.

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.

Primary outcomes:
measure: safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03）
timeFrame: 24 months
Secondary outcomes:
measure: Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
timeFrame: 24 months
measure: Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria）
timeFrame: 24 months
measure: Duration of Response （The time from response to relapse or progression）
timeFrame: 24 months
measure: Progression Free Survival （The time from the first day of treatment to the date on which disease progresses）
timeFrame: 24 months
measure: Overall Survival （The number of patient alive, with or without signs of cancer）
timeFrame: 24 months
Other outcomes:
Locations:
city: Haikou
country: China
facility: The Second Affiliated Hospital of Hainan Medical University
state: Hainan
Study officials:
affiliation: The Second Affiliated Hospital of Hainan Medical University
name: Haifeng Lin
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.