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

Non-hodgkin Lymphoma,B Cell Clinical Trial

Official title:

Adoptive Immunotherapy for Refractory/Relapsed Non-Hodgkin Lymphoma With CD19-TriCART Cells

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03720496
• Other study ID #: T2018-8
• Status: Recruiting
• Phase: Phase 1
• Start date: November 1, 2018
• Est. completion date: December 1, 2021

Study information

• Verified date: December 2019
• Source: Timmune Biotech Inc.
• Contact: Haifeng Lin
• Phone: +86 13322060949
• Email: 13322060949[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: December 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 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. 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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-hodgkin Lymphoma,B Cell

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
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)

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. — View 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. — 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

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