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

Adoptive Immunotherapy for Children CD19+ Leukemia and Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell

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.

Study Overview

• Status: Unknown
• Conditions: Leukemia; Non-Hodgkin Lymphoma of Intestine
• Intervention / Treatment: Biological: CD19-TriCAR-T/SILK

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 Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410005
      • Recruiting
      • Hunan Provincial People's Hospital
      • Contact: Xiangling He; Phone Number: +86 13873102615; Email: hexiangl@163.com
      • Contact: Keke Chen; Phone Number: +86 13974931408; Email: chenkeke1982@126.com
      • Principal Investigator: Xiangling He

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CD19-TriCAR-T/NK（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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safty (Incidence of treatment-related adverse events as assessed by CTCAE v4.03)	Incidence of treatment-related adverse events as assessed by CTCAE v4.03	24 monthes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	24 monthes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	24 monthes
Duration of Response （The time from response to relapse or progression）	The time from response to relapse or progression	24 monthes
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	24 monthes
Overall Survival （The number of patient alive, with or without signs of cancer）	The number of patient alive, with or without signs of cancer	24 monthes

Collaborators and Investigators

• Sponsor: Timmune Biotech Inc.
• Collaborators: Hunan Provincial People's Hospital
• Investigators: Principal Investigator: Xiangling He, Hunan Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 21, 2019
• Primary Completion (ANTICIPATED): April 15, 2022
• Study Completion (ANTICIPATED): October 15, 2022

Study Registration Dates

• First Submitted: April 8, 2019
• First Submitted That Met QC Criteria: April 8, 2019
• First Posted (ACTUAL): April 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2019
• Last Update Submitted That Met QC Criteria: September 5, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: CAR-T; children; Leukemia; Non-Hodgkin Lymphoma; CD19; TriCAR-T; TriCAR-SILK
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Leukemia; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: T2018-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No