Clinical trial NCT06613490: An Exploratory Clinical Study of CD19 CAR NK Cells for the Treatment of Refractory Antisynthetase Antibody Syndrome and Rheumatoid Arthritis
Official title: An Exploratory Clinical Study of the Safety and Efficacy of CD19 Chimeric Antigen Receptor NK Cells for the Treatment of Refractory Antisynthetase Antibody Syndrome and Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Antisynthetase Syndrome
Rheumatoid Arthritis
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Rui Therapeutics Co., Ltd
First posted: 2024-09-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A single-center, open-label dose-escalation design to evaluate the safety and efficacy of 3 infusions of anti CD19 CAR NK cells (KN5501), as well as the expansion and persistence of KN5501 in patients with refractory antisynthetase antibody syndrome (ASyS) and rheumatoid arthritis (RA); To evaluate the ability of KN5501 to clear CD19-positive B cells in patients to determine the feasibility of KN5501 for the treatment of refractory ASyS and or RA.


Eligibility criteria: Inclusion Criteria:

1. Subjects voluntarily sign the Informed Consent Form (ICF) , participate in this clinical study and be willing to follow and be able to complete all trial procedures.
2. Defined according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, adult patients with RA diagnosed ≥3 months prior to screening;Moderately to severely active RA;Poor response, or loss of response, or intolerance to at least one conventional synthetic DMARD (csDMARD) or biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD).
3. Defined according to the 2020 ENMC-DM classification diagnostic criteria. Adult patients with ASyS diagnosed ≥3 months prior to screening; patients with moderately severe active ASyS.
4. Age: ≥ 18 years old and ≤ 70 years old, male or female.
5. Subjects with estimated survival \> 12 weeks.
6. Serum creatinine clearance meets the relevant age/sex criteria, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN).
7. ECOG score 0 - 2.
8. The heart structure is essentially normal by echocardiography and Left ventricular ejection fraction (LVEF) ≥45%.
9. 2 weeks after the subject received the last dose treatment (hormonal, immunosuppressive or other experimental treatment).

Exclusion Criteria:

1. 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.
2. Subjects with one of the following genetic syndromes: Fanconi syndrome, Kostmann syndrome, Shwachman syndrome or any of the known bone marrow failure syndromes.
3. Subjects with Active or uncontrolled infections requiring parenteral antimicrobials; evidence of severe active viral or bacterial infections or uncontrolled systemic fungal infections.
4. Subjects with grade III or IV heart failure (NYHA classification).
5. History of epilepsy or other central nervous system (CNS) diseases.
6. Subjects with history of malignancy except cured of carcinoma in situ of the skin or cervix, and patients with inactive tumors.
7. Subjects with pronounced bleeding tendencies, such as gastrointestinal bleeding, coagulation disorders, and hypersplenism.
8. The subject with unstable angina, symptomatic congestive heart failure or myocardial infarction within the last 6 months.
9. Females who are pregnant, lactating, or planning a pregnancy within six months.
10. Subjects who have received other clinical trial treatment within 3 months.

Primary outcomes:
measure: Incidence of Dose-Limiting Toxicity (DLT)
timeFrame: up to 52 weeks after infusion
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: up to 52 weeks after infusion
Secondary outcomes:
measure: The overall response rate (ORR)
timeFrame: 4, 12, 24, 36 and 52 months after infusion
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
Study officials:
References: