Human CD19-CD22 Targeted T Cells Injection for Refractory/Relapsed Central Nervous System Leukemia/Lymphoma Patients

Study Overview
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Brief Summary
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This study is a single-arm, open-label, dose-escalation trial to explore the safety, tolerability and pharmacokinetic/pharmacodynamics characteristics of Human CD19-CD22 Targeted T Cells Injection, and to preliminarily observe the efficacy of the trial drug in patients with central nervous system involvement of refractory/relapsed B cell malignancies.

Detailed Description
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Subjects with refractory/relapsed central nervous system involvement of B cell malignancies can participate if all eligibility criteria are met. Tests required to determine eligibility including disease assessments, a physical exam, Electrocardiograph, Computed tomography (CT) / Magnetic Resonance Imaging (MRI) / Positron Emission Tomography (PET), Cerebrospinal fluid exam and blood draws. Subjects will receive preconditioning chemotherapy prior to the infusion of Human CD19-CD22 Targeted T Cells Injection. After the infusion, subjects will be followed for adverse events, pharmacokinetic/pharmacodynamics characteristics, efficacy of Human CD19-CD22 Targeted T Cells Injection. Study procedures may be performed while hospitalized.

Official Title
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A Early Phase 1 Clinical Trial To Evaluate the Safety and Efficacy of Human CD19-CD22 Targeted T Cells Injection for Subjects With Central Nervous System Involvement of Refractory/Relapsed B Cell Malignancies

Conditions
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Central Nervous System Lymphoma

Intervention / Treatment
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* Drug: Human CD19-CD22 Targeted T Cells Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Subjects must meet all of the following criteria to be enrolled: B cell malignancies patients with CD19 or CD22 positive, or CD19 and CD22 positive，include B cell acute lymphoblastic leukemia relapsed with central nervous system invasion and refractory/relapsed B cell lymphoma of central nervous system; 18 to 70 years old (including cut-off value), Male and female; Expected survival > 12 weeks; ECOG score 0-2; Definitive diagnosed as central nervous system of B cell malignancies by Cerebrospinal fluid and/or MRI, PET/CT or other imaging examinations; The venous access required for collection can be established and leukapheresis can be carried according to the judgement of investigators; Liver, kidney and cardiopulmonary functions meet the following requirements: The detection value of Creatinine within the normal range; Left ventricular ejection fraction > 50%; Baseline oxygen saturation > 92%; Total bilirubin ≤ 2×ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; Able to understand and sign the Informed Consent Document. Exclusion Criteria:Any one of the following conditions cannot be selected as a subject: Malignant tumors other than B cell malignancies within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, ductal carcinoma in situ after radical resection and thyroid cancer after radical resection; Subjects with positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titer detection higher than or equal to the lower limit of detection; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis detection positive; Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease; Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment; Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion; Received CAR-T treatment or other gene therapies before enrollment; Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell infusion; The investigators consider other conditions unsuitable for enrollment.

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: Human CD19-CD22 Targeted T Cells Injection<br>Single administration: 1.0×10^6 CAR+T cells/kg, 3.0×10^6 CAR+T cells/kg, 5.0×10^6 CAR+T cells/kg | Drug: Human CD19-CD22 Targeted T Cells Injection<br>* Autologous genetically modified anti-CD19/CD22 CAR transduced T cells<br>* Other names: CD19-CD22 CAR-T;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limited toxicity (DLT) | Safety Indicators | 28 days post infusion | 
| The occurrence rate of adverse events grade ≥ 3 assessed by NCI-CTCAE 5.0 | Safety Indicators | 28 days post infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics parameters - the highest concentration of Human CD19-CD22 Targeted T Cells amplified in peripheral blood after reinfusion | Effectiveness Metrics | 2 years post infusion | 
| Pharmacokinetics parameters - the time to reach the highest concentration of Human CD19-CD22 Targeted T Cells amplified in peripheral blood after reinfusion | Effectiveness Metrics | 2 years post infusion | 
| Pharmacokinetics parameters - the 28-day area under the curve of Human CD19-CD22 Targeted T Cells amplified in peripheral blood after reinfusion | Effectiveness Metrics | 2 years post infusion | 
| The rate of CAR-T cells in cerebrospinal fluid | Effectiveness Metrics | 2 years post infusion | 
| The duration of CAR-T cells in cerebrospinal fluid | Effectiveness Metrics | 2 years post infusion | 
| Pharmacodynamics characteristics - the detection values of IL-6, IFN-γ, IL-15 cytokines in peripheral blood | Effectiveness Metrics | 2 years post infusion | 
| Overall response rate (ORR) at 3 months after administration | Effectiveness Metrics | 3 months post infusion | 
| Duration of remission (DOR) after administration | Effectiveness Metrics | 2 years post infusion | 
| Overall Survival (OS) after administration | Effectiveness Metrics | 2 years post infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD19-CD22, CAR-T, Central nervous system leukemia/lymphoma, Refractory/Relapsed