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

NCT ID: NCT05651178

Last Updated: 2025-01-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-12
• Study Completion Date: 2025-08-31

Brief Summary

This study is a open-label, dose-escalation trial to explore the safety, tolerability and pharmacokinetic/pharmacodynamics characteristics of Human CD19-CD22 Targeted T Cells by intravenous and intrathecal administration, 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

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.

Conditions

Central Nervous System Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Human CD19-CD22 Targeted T Cells Injection

Intravenous 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. Intrathecal administration: The initial dose is set at 1 × 10⁶ CAR+cells per patient. The decision to escalate the intrathecal dose and frequency is made based on the condition of the subjects.

Group Type: EXPERIMENTAL

Human CD19-CD22 Targeted T Cells Injection

Intervention Type: DRUG

Autologous genetically modified anti-CD19/CD22 CAR transduced T cells

Interventions

Human CD19-CD22 Targeted T Cells Injection

Autologous genetically modified anti-CD19/CD22 CAR transduced T cells

Intervention Type: DRUG

Other Intervention Names

CD19-CD22 CAR-T

Eligibility Criteria

Inclusion Criteria

• 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:

1. The detection value of Creatinine within the normal range;

2. Left ventricular ejection fraction > 50%;

3. Baseline oxygen saturation > 92%;

4. Total bilirubin ≤ 2×ULN;

5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN;

• Able to understand and sign the Informed Consent Document.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: collaborator

Hrain Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Qingming Wang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital of Nanchang University

Locations

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xuedong Sun, M.D.

Role: CONTACT

sunxuedong@dashengbio.com

0086-021-58552006

Facility Contacts

Qingming Wang, M.D.

Role: primary

wqming222@163.com

0086-0791-86300483

Other Identifiers

HRAIN02-CNSL01

Identifier Type: -

Identifier Source: org_study_id