Natural Killer(NK) Cell Therapy 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 iPSC NK cells in patients with relapsed/refractory AML or AML Minimal Residual Disease (MRD).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CD33/CLL1 dual CAR-NK cell CLL1/CD33 dual CAR-NK cell therapy in Adult subjects with r/r AML |
Drug: CD33/CLL1 dual CAR-NK cell
NK cell therapy
Drug: Cyclophosphamid
Lympho-conditioning Agent
Drug: Fludarabine
Lympho-conditioning Agent
Drug: Cytarabine
Lympho-conditioning Agent
|
| Experimental: CD33 CAR-NK cell CD33 CAR-NK cell therapy in Adult subjects with r/r AML |
Drug: Cyclophosphamid
Lympho-conditioning Agent
Drug: Fludarabine
Lympho-conditioning Agent
Drug: Cytarabine
Lympho-conditioning Agent
Drug: CD33 CAR-NK cell
NK cell therapy
|
| Experimental: super NK cell super NK cell therapy in Adult subjects with AML MRD |
Drug: Cyclophosphamid
Lympho-conditioning Agent
Drug: Fludarabine
Lympho-conditioning Agent
Drug: Cytarabine
Lympho-conditioning Agent
Drug: super NK cell
NK cell therapy
|
Outcome Measures
Primary Outcome Measures
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [28 Days from first dose of iPSC NK cell infusion]
- Incidence of subjects with Dose Limiting Toxicities within each dose level cohort [28 Days from first dose of iPSC NK cell infusion]
Secondary Outcome Measures
- Overall Response Rate(ORR) [Up to approximately 2 years after last dose of iPSC NK cell infusion]
- MRD negative rate [28 Days from first dose of iPSC NK cell infusion]
- Event-free survival [Up to approximately 2 years after last dose of iPSC NK cell infusion]]
- Relapse-free survival [Up to approximately 2 years after last dose of iPSC NK cell infusion]
- Overall survival (OS) [Up to approximately 2 years after last dose of iPSC NK cell infusion]
- 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:
-
Provision of signed and dated informed consent form (ICF).
-
≥18 years old.
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Eastern Cooperative Oncology Group (ECOG) performance status ≤1 and life expectancy greater than 12 weeks.
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Diagnosis of r/r AML (Cohort 1 and 2) or AML MRD (Cohort 3).
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Cohort 1: Both CLL1 and CD33 expression are positive in AML blasts; Cohort 2: The expression of CD33 in AML blast is positive.
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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.
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 | Institute of Hematology & Blood Diseases Hospital | Tianjin | China |
Sponsors and Collaborators
- Institute of Hematology & Blood Diseases Hospital
- Hangzhou Qihan Biotech Co.,Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- QH-TJ-01