CAR-T for Children With Relapsed and Refractory Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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In this study, CAR-T will be administered to children with acute lymphoblastic leukemia to explore the effect of CAR-T intervention time on the duration of complete remission and further verify the long-term safety and efficacy of CAR-T treatment.

Detailed Description
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After clinician evaluation, if the child meets the study criteria and after adequate communication, the parent or legal guardian voluntarily joins the clinical study, CAR-T technique can be used for related treatment, and the long-term therapeutic effect can be observed. In this trial, 50 children were publicly enrolled and treated with CAR-T. Patients participating in the clinical trial will be tested and assessed in terms of treatment safety, efficacy, and duration of response.

Official Title
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An Open, Uncontrolled, Multicenter Clinical Trial to Explore the Safety, Efficacy, and Remission Phase of Chimeric Antigen Receptor T Cell (CAR-T) in the Treatment of Children With Relapsed and Refractory Acute Lymphoblastic Leukemia

Conditions
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Childhood Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: CD19 CAR-T
* Drug: CD22 CAR-T
* Drug: CD 19+22
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion criteria： The treat history meeting the following criteria: Recurrence of lymphoma patients with imaging (CT/MRI/PET-CT) detection and pathological diagnosis, or recurrence including bone marrow morphology relapse and the MRD recurrence of myeloma patients or leukemia patients, after chemotherapy or stem cell transplantation; Can't get complete remission (including MRD positive) after more than twice repeated chemotherapy of incipient lymphoma, myeloma or leukemia patients; One or twice chemotherapy cannot get remission again (including MRD positive), but not suitable for chemotherapy of incipient lymphoma, myeloma or leukemia patients. There is a measurable lesions before treatment at least; ECOG score≤2; To be aged 1 to 18 years; More than a month lifetime from the consent signing date Exclusion Criteria: Serious cardiac insufficiency, left ventricular ejection fraction<50%; Has a history of severe pulmonary function damaging; Merging other progressing malignant tumor; Merging uncontrolled infection; Merging the metabolic diseases (except diabetes); Merging severe autoimmune diseases or immunodeficiency disease; Patients with active hepatitis B or hepatitis C; Patients with HIV infection; Has a history of serious allergies on Biological products (including antibiotics); Has acute GvHD on allogeneic hematopoietic stem cell transplantation patients after stopping immunosuppressants a month; Any situation that would increase dangerousness of subjects or disturb the outcome of the clinical study according to the researcher's evaluation.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: volunteer<br>The child's parents or legal guardians voluntarily signed the informed consent form, and the child himself/herself met the enter criteria for the diagnosis of patients with acute B-lymphoblastic leukemia (B-ALL) expressing specific target antigens | Drug: CD19 CAR-T<br>* CD19 CAR-T infusion for pediatric patients with CD19 positive tumor cells<br>* Other names: Senl_19;Drug: CD22 CAR-T<br>* CD22 CAR-T infusion for pediatric patients with CD22 positive tumor cells<br>* Other names: Senl_22;Drug: CD 19+22<br>* CD19+22 CAR-T infusion for pediatric patients with CD19 positive and CD22 positive tumor cells<br>* Other names: Senl_19+22;Drug: Fludarabine<br>* 25mg/㎡ for D-4、D-3 and D-2<br>* Other names: flu;Drug: Cyclophosphamide<br>* 500mg/㎡ for D-3 and D-2<br>* Other names: ctx;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Severe/Adverse Events | Number of Participants with Severe/Adverse Events as a Measure of Safety diagnosis | 28 days | 
| CAR-T Cell expansion level | Copies numbers of CAR in peripheral blood(PB) and/or bone marrow(BM) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate of complete remission and partial remission | Objective response rate of complete remission and partial remission | 24 months | 
| Overall survival time | Overall survival time | 24 months |