Pilot CAR-T Cells Therapy for Children/Young Adults With CD19+ R/R Leukemia/Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to estimate the safety and the efficacy of CAR- T cells immunotherapy for children/young adults with relapsed or refractory acute lymphoblastic leukemia/lymphoma.

Detailed Description
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Locally manufactured second generation autologous CD19 CAR-T cells are used for immunotherapy. Protocol treatment includes lymphodepleting conditioning (fludarabine + cyclophosphamide) followed by one CAR-T cells intravenous infusion with tocilizumab premedication.

Official Title
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Pilot Study of CD19 CAR-T Cells Therapy for Relapsed or Refractory Acute Lymphoblastic Leukemia/Lymphoma in Children/Young Adults

Conditions
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B-cell Acute Lymphoblastic Leukemia, Lymphoblastic B-Cell Lymphoma

Intervention / Treatment
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* Biological: CD19 CAR-T-cells
* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CD19+ relapsed or refractory lymphoblastic leukemia/lymphoma; Karnofsky or Lansky performance scale greater or equal to 70; T-cells count in peripheral blood >150 cells/µL; Written informed consent. Exclusion Criteria: primary immunodeficiencies or genetic syndromes; neurologic diseases; autoimmune diseases or polyallergie; transfusion of donor lymphocyte less than 6 week before CAR-T cells infusion; GvHD grade 2-4; uncontrolled systemic infection; hypoxia (Sp02<90%) severe hepatic dysfunction: ALT or AST >=3x upper limit of normal for age; renal dysfunction: serum creatinine level >=3x upper limit of normal for age; positive serology for human immunodeficiency virus (HIV), active hepatite C or B; pregnancy.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 30 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: CD19 CAR-T cells immunotherapy<br>After a cycle of lymphodepleting chemotherapy a patient receive locally produced autologous CD19 CAR-T cells | Biological: CD19 CAR-T-cells<br>* One dose of CD19 CAR-T cells (1*10e6 CAR+ T-cells/kg) by intravenous infusion.<br>Drug: Tocilizumab<br>* Before 1h of CAR-T cells infusion a patient receive tocilizumab (8 mg/kg).<br>* Other names: Actemra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Adverse events will be graded according to the CTCAE v5.0 | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) (CR+CRi+CRm) | The proportion of patients with complete remission (CR), CR with incomplete hematologic recovery (CRi), complete molecular remission (CRm). | 28 days after CAR-T cells infusion | 
| Overall survival (OS) | The proportion of patients with overall survival | 1 year | 
| Events free survival (EFS) | Time from CAR-T cells infusion to CR failure, relapse, or death. | 1 year | 
| Leukemia free survival (LFS) | Time from achievement of CR/CRi/CRm to the time of relapse, death in remission, or last follow-up. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, CAR-T cells, CD19