Senl-h19 CAR-T Cell Injection in the Treatment of Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

Study Overview
=================
Brief Summary
-----------------
This study is an open, dose-escalating clinical study, taking patients with relapsed or refractory acute lymphoblastic leukemia as the test subjects, including mouse-derived CAR-T treatment failure or relapse, or for any reason cannot bridge the transplant r/r B-ALL.

Detailed Description
-----------------
Main research objectives: To evaluate the safety and efficacy of Senl-h19 CAR-T in patients with relapsed or refractory acute lymphoblastic leukemia Secondary research purpose To investigate the cytokinetic characteristics of Senl-h19 CAR-T in patients with relapsed or refractory acute lymphoblastic leukemia.

Official Title
-----------------
Senl-h19 CAR-T Cell Injection in the Treatment of Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

Conditions
-----------------
B-ALL

Intervention / Treatment
-----------------
* Biological: Senl-h19 CAR-T


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. 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; 2. A definite diagnosis of relapsed and refractory acute B-lymphoblastic leukemia meets one of the following criteria: a) Mouse CAR-T treatment fails or relapses; B) Unable to bridge the graft for any reason; 3. Eastern Cooperative Oncology Group (ECOG) score ≤2; 4. Age ≥2 years old, male or female 5. CD19 positive tumor cells were detected by immunohistochemistry or flow cytometry; 6. Expected survival longer than 3 months; 7. The collection time of peripheral blood mononuclear immune cells must be at least 2 weeks from the last radiotherapy or systematic treatment of patients; Exclusion Criteria: 1. Severe cardiac insufficiency; 2. Have a history of severe lung impairment; 3. Complicated with other advanced malignant tumors; 4. Complicated with severe or persistent infection that cannot be effectively controlled; 5. Complicated with severe autoimmune diseases or congenital immune deficiency; 6. Active hepatitis (HBVDNA or HCVRNA positive); Human immunodeficiency virus (HIV) infection or syphilis infection; 8. Have a history of severe allergy to biological products (including antibiotics); 9. The female patient is pregnant and lactating, or has a pregnancy plan within 12 months; 10. Conditions that the investigator believes may increase the risk to the subject or interfere with the outcome of the study.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Senl-h19 CAR-T<br>Patients will be treated with Senl-h19 CAR-T cells | Biological: Senl-h19 CAR-T<br>* Biological: Senl-h19 CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis<br>* Other names: CD19 CAR-T;|

What is the study measuring?
-----------------
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 CD7 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 | Remission Rate including complete remission(CR)、CR with incomplete blood count recovery(CRi)、No remission(NR) | 3 months post CAR-T cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of response (DOR) | duration of response (DOR) | 24 months post CAR-T cells infusion | 
| progression-free survival (PFS) | progression-free survival (PFS) time | 24 months post CAR-T cells infusion | 
| CAR-T proliferation | the copy number of Senl h19 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 | First 1 month post CAR-T cells infusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
B-ALL，h19，CAR-T