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

Early Phase 1

• Conditions: Non-Hodgkin Lymphoma
• Interventions: Biological: CD19-TriCAR-T/SILK

• Registration Number: NCT03790891
• Lead Sponsor: Timmune Biotech Inc.

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.

Study Timeline

• Study First Submitted: 2018-12-28
• Study First Submitted QC: 2018-12-28
• Study First Posted: 2019-01-02
• Study Start: 2019-01-05
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-11
• Last Update Posted: 2020-03-13
• Primary Completion: 2021-06-01
• Study Completion: 2022-01-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 12

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. 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;
4. At least one measurable lesion per revised IWG Response Criteria;
5. Aged <70 years;
6. Expected survival ≥12 weeks; Eastern cooperative oncology group (ECOG) performance status of≤2;
7. Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks;
8. All other treatment induced adverse events must have been resolved to ≤grade 1;
9. 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 hardly to control（defined by investigator）;
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 or women of childbearing age who plan to conceive during the time period;
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 consider the patient may not be suitable for the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD19-TriCAR-T/SILK	CD19-TriCAR-T/SILK	CD19-TriCAR-T/SILK cells will be administered intravenously

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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

Trial Locations

Locations (3)

Hainan Cancer Hospital; 🇨🇳 Haikou, Hainan, China

Hainan General Hospital; 🇨🇳 Haikou, Hainan, China

The Second Affiliated Hospital of Hainan Medical University; 🇨🇳 Haikou, Hainan, China