Treatment of Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell Therapy

Non-Hodgkin Lymphoma Clinical Trial

Official title:

Adoptive Immunotherapy for Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03790891
• Other study ID #: 2018-127
• Status: Recruiting
• Phase: Early Phase 1
• Start date: January 5, 2019
• Est. completion date: January 1, 2022

Study information

• Verified date: March 2020
• Source: Timmune Biotech Inc.
• Contact: Yao Hongxia
• Phone: +86 13876081106
• Email: yaohongxia768[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single arm, open-label, early phase Ⅰ study, to determine the safety and efficacy of CD19-TriCAR-T and CD19-TriCAR-SILK cell therapy in Non-Hodgkin lymphoma treatment.

Description:

CD19-TriCAR contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the CD19-TriCAR-T/SILK to simultaneously targeting the CD19 positive Non-Hodgkin lymphoma，blocking the inhibitory PD-L1 signal and stimulating innate T/NK cell activation and expansion, thus make it a tri-functional CAR (Tri-CAR). CD19-TriCAR-T is an autologous tri-functional CAR-T cell therapy, CD19-TriCAR-SILK is an Allogeneic tri-functional CAR-NK cell therapy, patients ineligible for leukapheresis or CAR-T therapy will be recommended for CD19-TriCAR-SILK therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: January 1, 2022
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 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. Refractory or relapsed malignant Non-Hodgkin lymphoma, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in standard chemotherapy; Disease progression or relapsed in =12 months of ASCT;

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

5. Aged <70 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 hardly to control(defined by investigator);

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin Lymphoma

Intervention

Biological:
• CD19-TriCAR-T/SILK
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide may be administered, followed by a single infusion of CD19-TriCAR-T cells or 4 repeat infusions of CD19-TriCAR-SILK cells.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Timmune Biotech Inc.

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View 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. Review. — View Citation

Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol. 2018 Mar 2;11(1):35. doi: 10.1186/s13045-018-0571-y. Review. Erratum in: J Hematol Oncol. 2018 Jun 13;11(1):81. — 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 for Malignant Lymphoma)	Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma	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