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

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

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).

Study Overview

• Status: Unknown
• Conditions: Non-hodgkin Lymphoma,B Cell
• Intervention / Treatment: Biological: CD19-TriCAR-T

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.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hainan
    • Haikou, Hainan, China, 570100
      • Recruiting
      • The Second Affiliated Hospital of Hainan Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CD19-TriCAR-T; Tri-functional anti-CD19 chimeric antigen receptor transduced autologous T cells will be administered intravenously	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Duration of Response （The time from response to relapse or progression）	The time from response to relapse or progression	24 months
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
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

Collaborators and Investigators

• Sponsor: Timmune Biotech Inc.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2018
• Primary Completion (ANTICIPATED): June 1, 2021
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: October 24, 2018
• First Submitted That Met QC Criteria: October 24, 2018
• First Posted (ACTUAL): October 25, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 9, 2019
• Last Update Submitted That Met QC Criteria: December 6, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: CAR-T; NHL; TriCAR-T; CD19-TriCAR-T; Non-hodgkin Lymphoma; CD19-CAR-T
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: T2018-8

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No