NCT03497533

Brief Summary

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).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Aug 2018

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 11, 2018

Completed
2 months until next milestone

First Posted

Study publicly available on registry

April 13, 2018

Completed
4 months until next milestone

Study Start

First participant enrolled

August 3, 2018

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2020

Completed
Last Updated

September 6, 2019

Status Verified

September 1, 2019

Enrollment Period

2.4 years

First QC Date

February 11, 2018

Last Update Submit

September 5, 2019

Conditions

Non-hodgkin Lymphoma,B Cell

Keywords

CD19CAR-TTriCAR-T-CD19non-Hodgkin lymphomaNHL

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (5)

  • Complete response rate[CR] (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)

    12 months

  • Duration of Response （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.）

    12 months

  • Overall Survival（The number of patient alive, with or without signs of cancer）

    24 months

Study Arms (1)

TriCAR-T-CD19

EXPERIMENTAL

Tri-functional anti-CD19 chimeric antigen receptor transduced autologous T cells will be administered intravenously

Biological: TriCAR-T-CD19

Interventions

TriCAR-T-CD19BIOLOGICAL

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

TriCAR-T-CD19

Eligibility Criteria

Age18 Years - 68 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • All subjects must personally sign and date the consent form before initiating any study specific procedures or activities;
  • All subjects must be able to comply with all the scheduled procedures in the study;
  • Histologically or cytologically confirmed CD19 positive non-Hodgkin lymphoma;
  • 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.
  • No available standard therapy;
  • At least one measurable lesion per revised IWG Response Criteria;
  • Aged 18 to 68 years;
  • Expected survival ≥12 weeks;
  • Eastern cooperative oncology group (ECOG) performance status of ≤2;
  • Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks;
  • All other treatment induced adverse events must have been resolved to ≤grade 1;
  • 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);
  • Female must be not pregnant during the study.

You may not qualify if:

  • 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;
  • History of allogeneic stem cell transplantation;
  • Prior other CAR therapy or other genetically modified T cell therapy;
  • 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;
  • Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases;
  • Lactating women;
  • Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive);
  • Subjects need systematic usage of corticosteroid;
  • History of any gene therapy;
  • Subjects need systematic usage of immunosuppressive drug;
  • Known history of infection with HIV;
  • Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study;
  • Other reasons the investigator think the patient may not be suitable for the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hunan Provincial People's Hospital

Changsha, Hunan, 410005, China

RECRUITING

Related 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.

    PMID: 21832238BACKGROUND

  • 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.

    PMID: 28129122RESULT

  • 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.

    PMID: 28925994RESULT

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Ming Zhou

    Hunan Provincial People's Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ming Zhou

CONTACT

+86 0731 83928147zhouming_0321@163.com

Bin Gao

CONTACT

+86 022 59060560bin.gao@timmune.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 11, 2018

First Posted

April 13, 2018

Study Start

August 3, 2018

Primary Completion

December 31, 2020

Study Completion

December 31, 2020

Last Updated

September 6, 2019

Record last verified: 2019-09

Locations

CN(1)