Treatment of Refractory/Relapsed Non-Hodgkin Lymphoma With TriCAR-T_CD19 (Trident19-H)

TriCAR-T-CD19 Adoptive Immunotherapy for CD19-positive Refractory/Relapsed Non-Hodgkin Lymphoma

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).

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410005
      • Recruiting
      • Hunan Provincial People's Hospital
      • Contact: Jianjun Chen; Phone Number: +86 0731 83928147
      • Contact: Ming Zhou; Phone Number: +86 0731 83928145; Email: zhouming_0321@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 68 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. 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.

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: TriCAR-T-CD19; Tri-functional anti-CD19 chimeric antigen receptor transduced autologous T cells will be administered intravenously	Biological: TriCAR-T-CD19; 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 0.5-1 x 10^6 CAR+ T cells/kg

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 v4.0)	Incidence of treatment-related adverse events as assessed by CTCAE v4.0	30 Days

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	12 months
Partial response rate [PR] (Partial response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)	Partial response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma	12 months
Duration of Response （The time from response to relapse or progression）	The time from response to relapse or progression	12 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.	12 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.
• Collaborators: Hunan Provincial People's Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 3, 2018
• Primary Completion (ANTICIPATED): December 31, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: February 11, 2018
• First Submitted That Met QC Criteria: April 10, 2018
• First Posted (ACTUAL): April 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2019
• Last Update Submitted That Met QC Criteria: September 5, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: CAR-T; NHL; non-Hodgkin lymphoma; CD19; TriCAR-T-CD19
• 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: ChiCTR1800014528

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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