Clinical trial NCT03910842: Treatment of Children CD19+ Leukemia and Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell Therapy
Official title: Adoptive Immunotherapy for Children CD19+ Leukemia and Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Non-Hodgkin Lymphoma of Intestine
Leukemia
Keywords: Non-Hodgkin Lymphoma
Leukemia
children
CD19
CAR-T
TriCAR-T
TriCAR-SILK
Lead sponsor: Timmune Biotech Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hunan Provincial People's Hospital
First posted: 2019-04-10
Enrollment: 12
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: safty (Incidence of treatment-related adverse events as assessed by CTCAE v4.03)
timeFrame: 24 monthes
Secondary outcomes:
measure: Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
timeFrame: 24 monthes
Other outcomes:
measure: Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria）
timeFrame: 24 monthes
measure: Duration of Response （The time from response to relapse or progression）
timeFrame: 24 monthes
measure: Progression Free Survival （The time from the first day of treatment to the date on which disease progresses）
timeFrame: 24 monthes
measure: Overall Survival （The number of patient alive, with or without signs of cancer）
timeFrame: 24 monthes
Locations:
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
Study officials:
affiliation: Hunan Provincial People's Hospital
name: Xiangling He
role: PRINCIPAL_INVESTIGATOR
References: