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

NCT05651178 | Recruiting Early Phase 1

• 1 other identifier: HRAIN02-CNSL01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Central Nervous System Lymphoma

Keywords

CD19-CD22; CAR-T; Central nervous system leukemia/lymphoma; Refractory/Relapsed

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Pharmacokinetics parameters - the highest concentration of Human CD19-CD22 Targeted T Cells amplified in peripheral blood after reinfusion

  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

  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

  2 years post infusion

• The rate of CAR-T cells in cerebrospinal fluid

  2 years post infusion

• The duration of CAR-T cells in cerebrospinal fluid

  2 years post infusion

Study Arms (1)

Human CD19-CD22 Targeted T Cells Injection

EXPERIMENTAL

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.

Drug: Human CD19-CD22 Targeted T Cells Injection

Interventions

Human CD19-CD22 Targeted T Cells Injection DRUG

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

Also known as: CD19-CD22 CAR-T

Human CD19-CD22 Targeted T Cells Injection

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hrain Biotechnology Co., Ltd.: lead
• Second Affiliated Hospital of Nanchang University: collaborator

Study Sites (1)

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

RECRUITING

MeSH Terms

Conditions

Lymphoma; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Qingming Wang, M.D.

  Second Affiliated Hospital of Nanchang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xuedong Sun, M.D.

CONTACT

0086-021-58552006; sunxuedong@dashengbio.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2022
• First Posted: December 14, 2022
• Study Start: August 12, 2022
• Primary Completion: November 30, 2024
• Study Completion: August 31, 2025
• Last Updated: January 7, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)