Treatment of Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell Therapy

Sponsor

Timmune Biotech Inc. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT03790891

Collaborator

(none)

Enrollment

Locations

Arm

35.9

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma	Biological: CD19-TriCAR-T/SILK	Early Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Adoptive Immunotherapy for Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell

Actual Study Start Date :

Jan 5, 2019

Anticipated Primary Completion Date :

Jun 1, 2021

Anticipated Study Completion Date :

Jan 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CD19-TriCAR-T/SILK CD19-TriCAR-T/SILK cells will be administered intravenously	Biological: CD19-TriCAR-T/SILK 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.

Arm

Intervention/Treatment

Experimental: CD19-TriCAR-T/SILK

CD19-TriCAR-T/SILK cells will be administered intravenously

Biological: CD19-TriCAR-T/SILK

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.

Outcome Measures

Primary Outcome Measures

safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03） [24 months]
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) [24 months]
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） [24 months]
Partial response rate per the revised International Working Group (IWG) Response Criteria
Duration of Response （The time from response to relapse or progression） [24 months]
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） [24 months]
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） [24 months]
The number of patient alive, with or without signs of cancer

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hainan Cancer Hospital	Haikou	Hainan	China	570100
2	Hainan General Hospital	Haikou	Hainan	China	570100
3	The Second Affiliated Hospital of Hainan Medical University	Haikou	Hainan	China	570100