Treatment of Children CD19+ Leukemia and Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell Therapy

Early Phase 1

• Conditions: Leukemia; Non-Hodgkin Lymphoma of Intestine
• Interventions: Biological: CD19-TriCAR-T/SILK

• Registration Number: NCT03910842
• 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 Children CD19+ Leukemia 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 Leukemia or 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

• Status Verified: 2019-03
• Study Start: 2019-03-21
• Study First Submitted: 2019-04-08
• Study First Submitted QC: 2019-04-08
• Study First Posted: 2019-04-10
• Last Update Submitted: 2019-09-05
• Last Update Posted: 2019-09-06
• Primary Completion: 2022-04-15
• Study Completion: 2022-10-15

Recruitment & Eligibility

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

Inclusion Criteria

For children CD19 positive B cell leukemia：

1. All subjects must personally sign and date the Informed Consent 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. CD19-positive B-cell leukemia with histology or cytology confirmed recurrence after treatment; or progression during treatment; or after first line treatment getting a MRD negative, 2 times of MRD show>0.01% but without bone marrow morphology recurrence;
4. At least one measurable lesion;
5. Aged <18 years; or diagnosised at the age of less than 18 and relapsed within three years， determined by the investigator;
6. Expected survival ≥12 weeks;
7. Eastern cooperative oncology group(ECOG) performance status of≤2;
8. Before CD19-TriCAR-T/SILK cell infusion, 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;

For children CD19 positive B cell lymphoma：

1. All subjects must personally sign and date the Informed Consent 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. CD19-positive B-cell lymphoma with histology or cytology confirmed recurrence after treatment，defined as one or more of the following: disease progression during standard therapy；recurrence after termination of treatment；relapse after autologous hematopoietic stem cell transplantation；not suitable for stem cell transplantation or abandon stem cell transplantation due to conditional restrictions;
4. At least one measurable lesion;
5. Aged <18 years; or diagnosised at the age of less than 18 and relapsed within three years， determined by the investigator;
6. Expected survival ≥12 weeks;
7. Eastern cooperative oncology group(ECOG) performance status of≤2;
8. Before CD19-TriCAR-T/SILK cell infusion, 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;

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 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/NK（SILK）	CD19-TriCAR-T/SILK	CD19-TriCAR-T/SILK cells will be administered intravenously

Primary Outcome Measures

Name	Time	Method
safty (Incidence of treatment-related adverse events as assessed by CTCAE v4.03)	24 monthes	Incidence of treatment-related adverse events as assessed by CTCAE v4.03

Secondary Outcome Measures

Name	Time	Method
Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)	24 monthes	Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma

Trial Locations

Locations (1)

Hunan Provincial People's Hospital; 🇨🇳 Changsha, Hunan, China