An Exploratory Clinical Study of the Safety and Efficacy of CD19 Chimeric Antigen Receptor NK Cell Injections for the Treatment of Relapsed/Refractory B-cell Related Autoimmune Diseases
Overview
- Phase
- Early Phase 1
- Intervention
- anti-CD19 CAR NK cells
- Conditions
- Autoimmune Diseases
- Sponsor
- YANRU WANG
- Enrollment
- 15
- Locations
- 2
- Primary Endpoint
- Treatment Emergent Adverse Events（TEAEs）
- Status
- Recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19 CAR NK cells (KN5501) in patients with relapsed/refractory B-cell related autoimmune diseases.15 patients are planned to be enrolled in the dose-escalation trial (6×10^9 cells, 9×10^9 cells). The primary objective of the study is to evaluation of the safety and feasibility of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases. The secondary objective is to evaluate the effectiveness of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases. The exploratory objective is to evaluate expansion, persistence and ability to deplete CD19 positive B cells of KN5501 in patients with relapsed/refractory B-cell related autoimmune diseases.
Investigators
YANRU WANG
Director, Department of Rheumatology and Immunology
Affiliated Hospital of Jiangsu University
Eligibility Criteria
Inclusion Criteria
- •Subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF) and are willing to follow and be able to complete all trial procedures
- •Subjects disease status of enrolment: not complete response (CR) after standard treatment; moderately to severely active autoimmune diseases
- •Age: ≥ 18 years old and ≤ 70 years old, male or female
- •Subjects with estimated survival \> 12 weeks
- •Adequate organs function: Serum creatinine clearance meets relevant age/sex criteria,aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN)
- •ECOG performance ≤ 2
- •Left ventricular ejection fraction (LVEF) ≥ 45%
- •Subjects have been treated with OCS in combination with an immunosuppressive or biologic agent for at least 2 weeks prior to enrollment
Exclusion Criteria
- •Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions
- •Subjects with one of the following genetic syndromes: Fanconi syndrome, Kostmann syndrome, Shwachman syndrome or any of the known bone marrow failure syndromes
- •Subjects with active or uncontrolled infections requiring parenteral antimicrobials; evidence of severe active viral or bacterial infections or uncontrolled systemic fungal infections
- •Subjects with grade III or IV heart failure (NYHA classification)
- •History of epilepsy or other central nervous system (CNS) diseases
- •History of other primary malignant tumors except: cured non-melanoma skin cancer or primary cervical cancer; subjects with inactive tumors
- •Subjects with more pronounced bleeding tendencies, such as gastrointestinal bleeding, coagulation disorders, and hypersplenism
- •Subjects were treated with systemic corticosteroids concomitantly within 2 weeks prior to treatment
- •Subjects with unstable angina, symptomatic congestive heart failure or myocardial infarction within the last 6 months
- •Females who are pregnant, lactating, or planning a pregnancy within six months
Arms & Interventions
anti-CD19 CAR NK cells
Intervention: anti-CD19 CAR NK cells
Outcomes
Primary Outcomes
Treatment Emergent Adverse Events（TEAEs）
Time Frame: within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion
To characterize the safety of anti-CD19 CAR NK Cells for moderate to severe autoimmune diseases
Incidence of Dose Limiting Toxicity (DLTs)
Time Frame: within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion
To characterize the safety of anti-CD19 CAR NK Cells for moderate to severe autoimmune diseases.
Secondary Outcomes
- Disease control rate of subjects(4, 12, 24, and 52 weeks after infusion)
- Remission rate of subjects(4, 12, 24, and 52 weeks after infusion)