Natural Killer(NK) Cell Therapy Targeting CLL1 in Acute Myeloid Leukemia
Study Details
Study Description
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 target CAR iPSC NK cells in patients with relapsed/refractory AML
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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. CLL-1 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 is an ideal target for AML.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CAR-NK cell therapy in Adult subjects with r/r AML CAR-NK cell therapy in Adult subjects with r/r AML |
Drug: CLL1 CAR-NK cell injection
Drug: CLL1 NK cell therapy Drug: Cyclophosphamid Lympho-conditioning Agent Drug: Fludarabine Lympho-conditioning Agent
Drug: VP-16 Lympho-conditioning Agent
|
Outcome Measures
Primary Outcome Measures
- Incidence of Treatment-Emergent Adverse Events [28 Days from first dose of iPSC NK cell infusion]
Safety and Tolerability
- Incidence of subjects with Dose Limiting Toxicities within each dose level cohort [28 Days from first dose of iPSC NK cell infusion]
Tolerability
Secondary Outcome Measures
- Determination of the pharmacokinetics (PK) of iPSC NK cells in peripheral blood [Up to approximately 2 years after last dose of iPSC NK cell infusion]
The PK of iPSC NK in peripheral blood will be reported as the relative percentage of product DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points
Eligibility Criteria
Criteria
Inclusion Criteria:
-
≥18 years old.
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Confirmed diagnosis of r/r AML
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CLL1 expression is positive in AML blasts.
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Eastern Cooperative Oncology Group (ECOG) performance status ≤1 and life expectancy greater than 12 weeks.
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Adequate organ and marrow function, as defined below:
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Blood creatinine (Cr) ≤ 2 x ULN or calculated creatinine clearance (Cockcroft- Gault formula) ≥ 50 mL/min;
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Total bilirubin (TBIL) ≤ 2 x the ULN;
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Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN;
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International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
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Females of childbearing potential must have a negative serum pregnancy test.
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Donor specific antibody (DSA) is negative: MFI <= 2000.
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Provision of signed and dated informed consent form (ICF).
Exclusion Criteria:
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Allergic to drug used in this study.
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Subjects received any antitumor therapy as follows, prior to first NK infusion:
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Systemic steroid therapy within 3 days (except physiological replacement therapy);
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Systemic antitumor therapy within 2 weeks or at least 5 half-lives, whichever is less;
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Radiotherapy within 4 weeks;
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Donor lymphocyte infusion within 6 weeks;
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Intrathecal treatment within 1 week;
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CAR-T therapy, CAR-NK therapy, or any other genetically modified cell therapy product within 6 months;
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History of allogeneic stem cell transplantation.
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Received the vaccine within 4 weeks prior to the first infusion and/or expected to require vaccination from the study period to 12 weeks after the last infusion.
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Active central nervous system Leukemia.
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Acute Promyelocytic Leukemia (APL).
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History of other malignant tumors, except for those who have achieved complete remission more than 5 years after radical treatment without any signs of recurrence.
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Active autoimmune diseases.
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History of central nervous system disease or meningeal involvement such as epilepsy, paralysis, aphasia, stroke, etc.
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Serious cardiovascular and cerebrovascular diseases:
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Severe heart rhythm or conduction abnormalities, corrected QT interval (QTc)≥480 ms;
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Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events within 6 months prior to first infusion;
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New York Heart Association (NYHA) class II or above congestive heart failure or left ventricular ejection fraction (LVEF) <50% in color Doppler echocardiography;
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Hypertension that cannot be controlled by drug.
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Active pulmonary infection; SpO2 ≤90%; Pulmonary embolism, chronic obstructive pulmonary disease, or interstitial lung disease.
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Uncontrolled bacterial, fungal, or viral infection. Known HIV infection, active Hepatitis B (HBV) or Hepatitis C (HCV) infection.
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History of substance abuse.
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Toxicity induced by previous therapy not recovered to ≤ grade 2(NCI-CTCAE v5.0).
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Large surgical treatment within 4 weeks prior to first infusion, not including diagnostic biopsy.
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Pregnant/breastfeeding women.
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Investigator-assessed presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical research ethics committee of the first affiliated hospital, college of medicine, zhejiang University | Hangzhou | Zhejiang | China |
Sponsors and Collaborators
- Zhejiang University
- Hangzhou Qihangene Biotech Co.,Ltd.
Investigators
- Principal Investigator: He Huang, MD, First Affiliated Hospital of Zhejiang University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- QH-CLL1-01