Clinical Study to Evaluate the Safety and Efficacy of iPSC -NK Cells Targeting CLL1 or CD33 in Patients With Relapsed/Refractory AML
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- AML, Adult
- Sponsor
- Zhejiang University
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a phase 1, first-in-human (FIH), open-label, multicohort study to evaluate the safety, tolerability and preliminary efficacy of CLL1 or CD33 target Chimeric antigen receptor (CAR) -induced pluripotent stem cells derived NK cells in patients with relapsed/refractory AML
Detailed Description
Acute myelogenous leukemia (AML) is a potentially cur-able disease; 70% of newly diagnosed patients achievecomplete remission with first-line therapy, but prognosisworsens for relapsed disease in both pediatric and adultpatients.C-type lectin-like molecule-1 and cluster of differentiation antigen 33 has attracted the researchers' attention due to its high expression in AML while being absent in normal hematopoietic stem cell. Accumulating evidence have demonstrated CLL-1 or CD33 is an ideal target for AML.
Investigators
He Huang
Professor
Zhejiang University
Eligibility Criteria
Inclusion Criteria
- •≥18 years old.
- •Confirmed diagnosis of r/r AML
- •CLL1 or CD33 expression is positive in AML blasts.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1 and life expectancy greater than 12 weeks.
- •Adequate organ and marrow function, as defined below:
- •Blood creatinine (Cr) ≤ 2 x ULN or calculated creatinine clearance (Cockcroft- Gault formula) ≥ 50 mL/min;
- •Total bilirubin (TBIL) ≤ 2 x the ULN;
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN;
- •International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN 6.Females of childbearing potential must have a negative serum pregnancy test. 7.Donor specific antibody (DSA) is negative: MFI \<=
- •8.Provision of signed and dated informed consent form (ICF).
Exclusion Criteria
- •Allergic to drug used in this study.
- •Subjects received any antitumor therapy as follows, prior to first NK infusion:
- •a. Systemic steroid therapy within 3 days (except physiological replacement therapy):b. Systemic antitumor therapy within 2 weeks or at least 5 half-lives, whichever is less; c. Radiotherapy within 4 weeks; d. Donor lmphocyte infusion within 6 weeks: e. Intrathecal treatment within 1 week; f CAR-T therapy, CAR-NK therapy, or any other genetically modified cell therapy product within 6 months;
- •History of allogeneic stem cell transplantation.
- •Received the vaccine within 4 weeks pror to the first infusion andor expected to reuire vaccination from the study period to 12 weeks ater the last intusion
- •Active central nervous system Leukemia.
- •Acute Promyelocytic Leukemia (APL).
- •.History of other malicnant tumors, except for those who have achieved omplete remission more than 5 years after radical treatment without any sions of recurence
- •History of central nervous system disease or meningeal involvement such as epilepsy, paralysis, aphasia, stroke, etc
- •Active autoimmune diseases.
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events
Time Frame: 28 Days from first dose of iPSC NK cell infusion
Safety and Tolerability