Anti-CD19 CAR-T Cells for Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphomas

Study Overview
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Brief Summary
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This is a single arm, open-label, single center study to determine the safety and efficacy of Anti-CD19 CAR-T cells in patients with relapsed or refractory acute lymphoblastic leukemia and Lymphomas.

Detailed Description
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CD19 has been extensively evaluated as a therapeutic target for relapsed or refractory B cell malignancy by chimeric antigen receptor T cell therapy,this is a single arm, open-label, single center study to determine the safety and efficacy of Anti-CD19 CAR-T cells in patients with refractory acute lymphoblastic leukemia and Lymphomas.

Official Title
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Study Evaluating the Safety and Efficacy With Anti-CD19 CAR-T Cells for Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphomas

Conditions
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Acute Lymphoblastic Leukemia ,Lymphomas

Intervention / Treatment
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* Biological: Anti-CD19 CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed as Relapsed or Refractory acute lymphoblastic leukemia and Lymphomas ，and have no effective treatment option (such as autograft or allogeneic stem cell transplantation) and estimated survival time of the current treatment < 2 years, The specific requirements are as follows: Male or female aged 18-70 years old ; Estimated Survival time > 12 weeks; Relapsed and refractory acute lymphoblastic leukemia and lymphoma were confirmed by physical examination, pathological examination, laboratory examination and imaging; Chemotherapy failure or recurrent acute lymphoblastic leukemia and Lymphomas; Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase< 3 fold of normal level; Bilirubin<2.0mg/dl; Karnofsky Performance Status>50% at the time of screening; Adequate pulmonary, renal, hepatic, and cardiac function; Fail in autologous or allogenic haemopoietic stem cell transplantation; Not suitable for stem cell transplantation conditions or abandoned due to conditions; Free of leukocytes removal contraindications; Voluntarily join CAR-T clinical trial ,Understand and sign written informed consent. Exclusion Criteria: The patient is a pregnant or breastfeeding woman, or is a woman with a pregnancy plan within six months; Patients have infectious diseases (such as HIV, active tuberculosis, etc.); The patient is an active hepatitis B or hepatitis C infection; Feasibility assessment proves that the efficiency of transduction of lymphocyte is below 10% or the lymphocyte cannot be propagated ; Abnormal vital signs; Subjects with mental or psychological illness who cannot be combined with treatment and efficacy evaluation; Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2; General infection or local severe infection, or other infection that is not controlled; Dysfunction in lung, heart, kidney and brain; Severe autoimmune diseases; Other symptoms that are not applicable for CAR-T.

Ages Eligible for Study
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Minimum Age: 18 Years
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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-CD19 CAR-T<br>Anti-CD19 CAR-T | Biological: Anti-CD19 CAR-T<br>* 1 - 2×10^6 Anti-CD19 CAR-T cells/kg body weigh<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall responce rate(ORR) | Assessment of ORR (ORR = CR+PR ) at 2 months of treatment | 2 years | 
| Overall survival (OS) | Assessment of OS(Overall survival) at 6 months of treatment | 2 years | 
| Progression-free survival (PFS) | Assessment of PFS(Progression-free survival ) at 6 months of treatment | 2 years | 
| minimal residual disease（MRD） | Assessment of MRD negative overall response rate at 3 months of treatment | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (incidence of adverse events defined as dose-limited toxicity) | Occurrence of study related adverse events defined as NCI CTCAE 4.0 > grade 3 possibly, probably, or definitely related to study treatment. | Study treatment until Week 24 | 
| Expression of CD19 CART cells | Expression of CD19 CART cells detected by flow cytometry in blood and bone marrow. | 2 years | 
| Detection of CD19 CART cells | Detection of CD19 CART cells in blood, bone marrow by Quantitative Polymerase Chain Reaction (q-PCR). | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute lymphoblastic leukemia ;Lymphomas