Back to resultsTreatment of Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell Therapy
Primary Purpose
Non-Hodgkin Lymphoma
Status
Unknown status
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
CD19-TriCAR-T/SILK
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkin Lymphoma focused on measuring CAR-T, TriCAR-T, CD19-TriCAR-T, CD19-TriCAR-SILK, Non-Hodgkin Lymphoma
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;
- Refractory or relapsed malignant Non-Hodgkin lymphoma, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in standard chemotherapy; Disease progression or relapsed in ≤12 months of ASCT;
- At least one measurable lesion per revised IWG Response Criteria;
- Aged <70 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 hardly to control（defined by investigator）;
- 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 or women of childbearing age who plan to conceive during the time period;
- 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 consider the patient may not be suitable for the study.
Sites / Locations
- Hainan Cancer HospitalRecruiting
- Hainan General HospitalRecruiting
- The Second Affiliated Hospital of Hainan Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CD19-TriCAR-T/SILK
Arm Description
CD19-TriCAR-T/SILK 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
1. Study Identification
Unique Protocol Identification Number
NCT03790891
Brief Title
Treatment of Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell Therapy
Official Title
Adoptive Immunotherapy for Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 5, 2019 (Actual)
Primary Completion Date
June 1, 2021 (Anticipated)
Study Completion Date
January 1, 2022 (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, early phase Ⅰ study, to determine the safety and efficacy of CD19-TriCAR-T and CD19-TriCAR-SILK cell therapy in Non-Hodgkin lymphoma treatment.
Detailed Description
CD19-TriCAR contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the CD19-TriCAR-T/SILK to simultaneously targeting the CD19 positive Non-Hodgkin lymphoma，blocking the inhibitory PD-L1 signal and stimulating innate T/NK cell activation and expansion, thus make it a tri-functional CAR (Tri-CAR). CD19-TriCAR-T is an autologous tri-functional CAR-T cell therapy, CD19-TriCAR-SILK is an Allogeneic tri-functional CAR-NK cell therapy, patients ineligible for leukapheresis or CAR-T therapy will be recommended for CD19-TriCAR-SILK therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin Lymphoma
Keywords
CAR-T, TriCAR-T, CD19-TriCAR-T, CD19-TriCAR-SILK, Non-Hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CD19-TriCAR-T/SILK
Arm Type
Experimental
Arm Description
CD19-TriCAR-T/SILK cells will be administered intravenously
Intervention Type
Biological
Intervention Name(s)
CD19-TriCAR-T/SILK
Intervention Description
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide may be administered, followed by a single infusion of CD19-TriCAR-T cells or 4 repeat infusions of CD19-TriCAR-SILK cells.
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
70 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;
Refractory or relapsed malignant Non-Hodgkin lymphoma, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in standard chemotherapy; Disease progression or relapsed in ≤12 months of ASCT;
At least one measurable lesion per revised IWG Response Criteria;
Aged <70 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 hardly to control（defined by investigator）;
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 or women of childbearing age who plan to conceive during the time period;
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 consider the patient may not be suitable for the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yao Hongxia
Phone
+86 13876081106
Email
yaohongxia768@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Gao Bin
Phone
+86 13910899150
Email
bin.gaoa@timmune.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yao Hongxia
Organizational Affiliation
Hainan General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hainan Cancer Hospital
City
Haikou
State/Province
Hainan
ZIP/Postal Code
570100
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuyang Tian
Phone
+86 18686853849
Email
tianyuyang@163.com
Facility Name
Hainan General Hospital
City
Haikou
State/Province
Hainan
ZIP/Postal Code
570100
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yao Hongxia
Phone
+86 13876081106
Email
yaohongxia768@163.com
First Name & Middle Initial & Last Name & Degree
Wu Yasong
Phone
+86 18020091931
Email
yasong.wu@timmune.com
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
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
background
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
29499750
Citation
Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol. 2018 Mar 2;11(1):35. doi: 10.1186/s13045-018-0571-y. Erratum In: J Hematol Oncol. 2018 Jun 13;11(1):81.
Results Reference
background
Learn more about this trial
Treatment of Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell Therapy
We'll reach out to this number within 24 hrs