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

Primary Purpose

Non-hodgkin Lymphoma,B Cell

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CD19-TriCAR-T
Sponsored by
Timmune Biotech Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-hodgkin Lymphoma,B Cell focused on measuring CAR-T, TriCAR-T, CD19-TriCAR-T, Non-hodgkin Lymphoma, NHL, CD19-CAR-T

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Second Affiliated Hospital of Hainan Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CD19-TriCAR-T

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
Duration of Response （The time from response to relapse or progression）
The time from response to relapse or progression
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
Overall Survival （The number of patient alive, with or without signs of cancer）
The number of patient alive, with or without signs of cancer

Full Information

First Posted
October 24, 2018
Last Updated
December 6, 2019
Sponsor
Timmune Biotech Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03720496
Brief Title
Treatment of Refractory/Relapsed Non-Hodgkin Lymphoma With CD19-TriCART Cell Therapy
Official Title
Adoptive Immunotherapy for Refractory/Relapsed Non-Hodgkin Lymphoma With CD19-TriCART Cells
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2018 (Actual)
Primary Completion Date
June 1, 2021 (Anticipated)
Study Completion Date
December 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Timmune Biotech Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-hodgkin Lymphoma,B Cell
Keywords
CAR-T, TriCAR-T, CD19-TriCAR-T, Non-hodgkin Lymphoma, NHL, CD19-CAR-T

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CD19-TriCAR-T
Arm Type
Experimental
Arm Description
Tri-functional anti-CD19 chimeric antigen receptor transduced autologous T cells will be administered intravenously
Intervention Type
Biological
Intervention Name(s)
CD19-TriCAR-T
Intervention Description
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.
Primary Outcome Measure Information:
Title
safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03）
Description
Incidence of treatment-related adverse events as assessed by CTCAE v4.03
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
Description
Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma
Time Frame
24 months
Title
Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria）
Description
Partial response rate per the revised International Working Group (IWG) Response Criteria
Time Frame
24 months
Title
Duration of Response （The time from response to relapse or progression）
Description
The time from response to relapse or progression
Time Frame
24 months
Title
Progression Free Survival （The time from the first day of treatment to the date on which disease progresses）
Description
The time from the first day of treatment to the date on which disease progresses
Time Frame
24 months
Title
Overall Survival （The number of patient alive, with or without signs of cancer）
Description
The number of patient alive, with or without signs of cancer
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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; At least one measurable lesion per revised IWG Response Criteria; Aged 18 to 69 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); Exclusion Criteria: 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; 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; Lactating women; Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive); Known history of infection with HIV; Subjects need systematic usage of corticosteroid; Subjects need systematic usage of immunosuppressive drug; 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Haifeng Lin
Phone
+86 13322060949
Email
13322060949@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Bin Gao, Dr.
Phone
+86 022 59060560
Email
bin.gao@timmune.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Haifeng Lin
Organizational Affiliation
The Second Affiliated Hospital of Hainan Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Affiliated Hospital of Hainan Medical University
City
Haikou
State/Province
Hainan
ZIP/Postal Code
570100
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Haifeng Lin
Phone
+86 13322060949
Email
13322060949@163.com
First Name & Middle Initial & Last Name & Degree
Yasong Wu
Phone
+86 18020091931
Email
yasong.wu@timmune.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28129122
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.
Results Reference
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PubMed Identifier
28925994
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.
Results Reference
background
PubMed Identifier
21832238
Citation
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.
Results Reference
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Treatment of Refractory/Relapsed Non-Hodgkin Lymphoma With CD19-TriCART Cell Therapy

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