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

NCT ID: NCT03790891

Last Updated: 2020-03-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

EARLY_PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-05

Study Completion Date

2022-01-01

Brief Summary

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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

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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.

Conditions

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Non-Hodgkin Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CD19-TriCAR-T/SILK

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

Group Type EXPERIMENTAL

CD19-TriCAR-T/SILK

Intervention Type BIOLOGICAL

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.

Interventions

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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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Timmune Biotech Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yao Hongxia

Role: PRINCIPAL_INVESTIGATOR

Hainan General Hospital

Locations

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Hainan Cancer Hospital

Haikou, Hainan, China

Site Status RECRUITING

Hainan General Hospital

Haikou, Hainan, China

Site Status RECRUITING

The Second Affiliated Hospital of Hainan Medical University

Haikou, Hainan, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Yao Hongxia

Role: CONTACT

+86 13876081106

Gao Bin

Role: CONTACT

+86 13910899150

Facility Contacts

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Yuyang Tian

Role: primary

+86 18686853849

Yao Hongxia

Role: primary

+86 13876081106

Wu Yasong

Role: backup

+86 18020091931

Haifeng Lin

Role: primary

+86 13322060949

References

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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.

Reference Type BACKGROUND
PMID: 28129122 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28925994 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29499750 (View on PubMed)

Other Identifiers

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2018-127

Identifier Type: -

Identifier Source: org_study_id

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