Clinical trial NCT05987696: Natural Killer(NK) Cell Therapy in Acute Myeloid Leukemia
Official title: Phase I Study to Evaluate the Safety and Efficacy of NK Cell Therapy in Acute Myeloid Leukemia (AML).
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: AML, Adult
Minimal Residual Disease
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Hangzhou Qihan Biotech Co.,Ltd.
First posted: 2023-08-14
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

1. Provision of signed and dated informed consent form (ICF).
2. ≥18 years old.
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 and life expectancy greater than 12 weeks.
4. Diagnosis of r/r AML (Cohort 1 and 2) or AML MRD (Cohort 3).
5. Cohort 1: Both CLL1 and CD33 expression are positive in AML blasts; Cohort 2: The expression of CD33 in AML blast is positive.
6. Adequate organ and marrow function, as defined below:

   1. Blood creatinine (Cr) ≤ 2 x ULN or calculated creatinine clearance (Cockcroft-Gault formula) ≥ 50 mL/min;
   2. Total bilirubin (TBIL) ≤ 2 x the ULN;
   3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN;
   4. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN;
7. Females of childbearing potential must have a negative serum pregnancy test.
8. Donor specific antibody (DSA) is negative: MFI \<= 2000.

Exclusion Criteria:

1. Allergic to drug used in this study.
2. Subjects received any antitumor therapy as follows, prior to first NK infusion:

   1. Systemic steroid therapy within 3 days (except physiological replacement therapy);
   2. Systemic antitumor therapy within 2 weeks or at least 5 half-lives, whichever is less;
   3. Radiotherapy within 4 weeks;
   4. Donor lymphocyte infusion within 6 weeks;
   5. Intrathecal treatment within 1 week;
   6. CAR-T therapy, CAR-NK therapy, or any other genetically modified cell therapy product within 6 months;
3. History of allogeneic stem cell transplantation.
4. 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.
5. Active central nervous system Leukemia.
6. Acute Promyelocytic Leukemia (APL).
7. 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.
8. Active autoimmune diseases.
9. History of central nervous system disease or meningeal involvement such as epilepsy, paralysis, aphasia, stroke, etc.
10. Serious cardiovascular and cerebrovascular diseases:

    1. Severe heart rhythm or conduction abnormalities, corrected QT interval (QTc)≥480 ms;
    2. 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;
    3. New York Heart Association (NYHA) class II or above congestive heart failure or left ventricular ejection fraction (LVEF) \<50% in color Doppler echocardiography;
    4. Hypertension that cannot be controlled by drug.
11. Active pulmonary infection; SpO2 ≤90%; Pulmonary embolism, chronic obstructive pulmonary disease, or interstitial lung disease.
12. Uncontrolled bacterial, fungal, or viral infection. Known HIV infection, active Hepatitis B (HBV) or Hepatitis C (HCV) infection.
13. History of substance abuse.
14. Toxicity induced by previous therapy not recovered to ≤ grade 2(NCI-CTCAE v5.0).
15. Large surgical treatment within 4 weeks prior to first infusion, not including diagnostic biopsy.
16. Pregnant/breastfeeding women.
17. Investigator-assessed presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 28 Days from first dose of iPSC NK cell infusion
measure: Incidence of subjects with Dose Limiting Toxicities within each dose level cohort
timeFrame: 28 Days from first dose of iPSC NK cell infusion
Secondary outcomes:
measure: Overall Response Rate(ORR)
timeFrame: Up to approximately 2 years after last dose of iPSC NK cell infusion
measure: MRD negative rate
timeFrame: 28 Days from first dose of iPSC NK cell infusion
measure: Event-free survival
timeFrame: Up to approximately 2 years after last dose of iPSC NK cell infusion]
measure: Relapse-free survival
timeFrame: Up to approximately 2 years after last dose of iPSC NK cell infusion
measure: Overall survival (OS)
timeFrame: Up to approximately 2 years after last dose of iPSC NK cell infusion
measure: Determination of the pharmacokinetics (PK) of iPSC NK cells in peripheral blood
timeFrame: Up to approximately 2 years after last dose of iPSC NK cell infusion
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
Study officials:
References: