Clinical trial NCT04191941: Treatment of Hematological Malignancy With Novel CAR-T Cells.
Official title: Adoptive Immunotherapy for Hematological Malignancy With Novel CAR-T Cells.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: B-cell Non Hodgkin Lymphoma
B-cell Acute Lymphoblastic Leukemia
Multiple Myeloma
Keywords: CD19-TriCAR-T
1922-TriCAR-T
BCMA-TriCAR-T
Lead sponsor: Timmune Biotech Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hunan Provincial People's Hospital
First posted: 2019-12-10
Enrollment: 9
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Novel CAR-T Cell Therapy
Primary purpose: TREATMENT

Brief summary: This is a single arm, open-label, early phase I study, to determine the safety and efficacy of Novel CAR-T cell therapy in Hematological Malignancy treatment.

Detailed description: The Novel CAR-T contains either a scFv plus a PD-L1 blocker, or two scFvs, in a cytokine complex based outer memberane structure, this kind of structure enables the CAR-T cells to simultaneously target one or two targets on the tumor cell surface and enhance CAR-T cell persistence in tumor microenvironment，as well as stimulating innate T/NK cell activation and expansion.

Eligibility criteria: 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. Clear diagnosis of hematological malignancy, including B-cell Non-Hodgkin lymphoma, B-cell lymphoblastic leukemia, multiple myeloma.
4. Fufill one or more of the following criteria: Relapsed after most recent therapy; Progressive disease in standard chemotherapy; Disease progression or relapsed after ASCT;
5. At least one clear indicator for hematological malignancy monitoring;
6. Aged \<70 years;
7. Expected survival ≥12 weeks;
8. Eastern cooperative oncology group (ECOG) performance status of≤3;
9. Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks;
10. All other treatment induced adverse events must have been resolved to

    ≤grade 1;
11. 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 investigational 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: safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.03)
timeFrame: 3 months
Secondary outcomes:
measure: Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
timeFrame: 3 months
measure: Partial response rate [PR] (Partial response rate per the revised International Working Group (IWG) Response Criteria)
timeFrame: 3 months
measure: Duration of Response (The time from response to relapse or progression)
timeFrame: 24 months
measure: Progression Free Survival (The time from the first day of treatment to the date on which disease progresses)
timeFrame: 24 months
measure: Overall Survival (The number of patient alive, with or without signs of cancer)
timeFrame: 24 months
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
Study officials:
affiliation: Hunan Provincial People's Hospital
name: Ming Zhou
role: PRINCIPAL_INVESTIGATOR
References: