The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies

Study Overview
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Brief Summary
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To evaluate the tolerability and safety of CAR-T technology in patients with relapsed or refractory hematolymphoid malignancies.

Detailed Description
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Main research purposes: To evaluate the tolerability and safety of CAR-T technology in patients with relapsed or refractory hematolymphoid malignancies. Secondary research purposes: Objective Evaluation of Cytodynamic Characteristics of CAR-T in Different Types of Hematological Malignancies

Official Title
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The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies

Conditions
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Acute Lymphoblastic Leukemia, Lymphoma, Multiple Myeloma

Intervention / Treatment
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* Biological: CAR-T Autologous T cell injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent and be willing and able to comply with the visit, treatment protocol, laboratory examination, and other requirements of the study as specified in the study procedure sheet; Diagnosed as recurrent or refractory lymphoma, leukemia or myeloma; Tumor cells express targets for CAR-T cell therapy (results: flow cytometry or Immunohistochemical test confirmation); Age 14-75 (including threshold), gender unlimited; Eastern Cooperative Oncology Group (ECOG) score ≤2; HGB ≥ 70g/L (blood transfusion allowed); Liver and kidney functions, heart and lung functions meet the following requirements: Creatinine ≤ 1.5 × ULN; Left ventricular ejection fraction ≥ 50%; Blood oxygen saturation>90%; Total bilirubin ≤ 1.5 × ULN； ALT and AST ≤ 2.5 × ULN; For T cell tumor patients, if tumor cells are detected in peripheral blood during screening, flow cytometry should be used to detect that the tumor cell surface immunophenotype is CD4 and CD8 double negative. If the immunophenotype of peripheral blood tumor cells is not double negative for CD4 and CD8, the condition that the proportion of peripheral blood tumor cells is ≤ 1% shall be met; Subjects with pregnancy plans must agree to use contraception before entering the study and after the study lasts for six months; If the subject is pregnant or suspected of being pregnant, the investigator shall be informed immediately; The subject or guardian understands and signs the informed consent form; Expected survival longer than 3 months. Exclusion Criteria: Severe cardiac insufficiency; Have a history of severe lung impairment; Complicated with other advanced malignant tumors; Complicated with severe or persistent infection that cannot be effectively controlled; Complicated with severe autoimmune diseases or congenital immune deficiency; Active hepatitis (HBV DNA or HCV RNA positive); Human immunodeficiency virus (HIV) infection or syphilis infection; Have a history of severe allergy to biological products (including antibiotics); If there is a history of hematopoietic stem cell transplantation, it should be no more than 6 months before the patient receives allogeneic hematopoietic stem cell transplantation; Subjects who received CAR-T therapy or other gene modified cell therapy before screening; Conditions that the investigator believes may increase the risk to the subject or interfere with the outcome of the study.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 75 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAR-T Autologous T cell injection<br>Patients will be treated with CAR-T cells | Biological: CAR-T Autologous T cell injection<br>* Biological: CAR-T; Drug: Cyclophosphamide,Fludarabine；Procedure: Leukapheresis<br>* Other names: BCMA CAR-T;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence and severity of adverse events | To evaluate the possible adverse events occurred within first one month after CAR-T infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity | First 1 month post CAR-T cells infusion | 
| Efficacy: Remission Rate | Complete remission (CR) Complete remission with incomplete recovery of blood cells (CRI), positive minimal residual tumor (MRD+) or negative tumor (MRD -) CR/CRI, disease recurrence or progression (PD) were evaluated, and the overall remission rate was ORR=CR+CRI; For drenching Complete remission (CR), partial remission (PR), disease stability (SD) Disease recurrence or progression (PD) was evaluated, and the overall remission rate was ORR=CR+PR; For multiple myeloma Complete remission (CR), partial remission (VGPR, PR), disease stability (SD), disease recurrence or progression (PD) were adopted, Overall remission rate ORR=CR+VGPR+PR; | 3 months post CAR-T cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) | progression-free survival (PFS) time | 24 months post CAR-T cells infusion | 
| CAR-T proliferation | the copy number of Senl CAR- T cells in the genomes of PBMC by qPCR method | 3 months post CAR-T cells infusion | 
| Cytokine release | Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method | 1 month post CAR-T cells infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD19,CD20,BCMA, B-ALL/MM/NHL