Treatment of Hematological Malignancy With Novel CAR-T Cells.

Study Overview
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Brief Summary
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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
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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.

Official Title
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Adoptive Immunotherapy for Hematological Malignancy With Novel CAR-T Cells.

Conditions
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B-cell Non Hodgkin Lymphoma, B-cell Acute Lymphoblastic Leukemia, Multiple Myeloma

Intervention / Treatment
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* Biological: Novel CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects must personally sign and date the consent form before initiating any study specific procedures or activities; All subjects must be able to comply with all the scheduled procedures in the study; Clear diagnosis of hematological malignancy, including B-cell Non-Hodgkin lymphoma, B-cell lymphoblastic leukemia, multiple myeloma. Fufill one or more of the following criteria: Relapsed after most recent therapy; Progressive disease in standard chemotherapy; Disease progression or relapsed after ASCT; At least one clear indicator for hematological malignancy monitoring; Aged <70 years; Expected survival ≥12 weeks; Eastern cooperative oncology group (ECOG) performance status of≤3; Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks; All other treatment induced adverse events must have been resolved to ≤grade 1; 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: Presence of fungal, bacterial, viral, or other infection that is hardly to control (defined by investigator); 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; Lactating women or women of childbearing age who plan to conceive during the investigational time period; Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive); Known history of infection with HIV; Subjects need systematic usage of corticosteroid; Subjects need systematic usage of immunosuppressive drug; Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study; Other reasons the investigator consider the patient may not be suitable for the study.

Ages Eligible for Study
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Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Novel CAR-T Cell Therapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Novel CAR-T<br>Novel CAR-T cells will be administered intravenously | Biological: Novel CAR-T<br>* A conditioning chemotherapy regimen of fludarabine and cyclophosphamide may be administered, followed by a single infusion of Novel CAR-T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.03) | Incidence of treatment-related adverse events as assessed by CTCAE v4.03 | 3 months | 

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 | 3 months | 
| 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 | 3 months | 
| Duration of Response (The time from response to relapse or progression) | The time from response to relapse or progression | 24 months | 
| 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 months | 
| 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 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD19-TriCAR-T, 1922-TriCAR-T, BCMA-TriCAR-T