Natural Killer(NK) Cell Therapy Targeting CLL1 or CD33 in Acute Myeloid Leukemia

Launched by ZHEJIANG UNIVERSITY · Apr 11, 2024

Keywords

ClinConnect Summary

This clinical trial is exploring a new treatment for adults with a type of blood cancer called Acute Myeloid Leukemia (AML) that has come back or has not responded to previous treatments. The study is testing a special type of immune cell therapy, using natural killer (NK) cells that are modified to target specific markers on cancer cells. The main goal is to see if this treatment is safe and how well it works.

To participate, you need to be at least 18 years old and have a confirmed diagnosis of relapsed or refractory AML with certain markers present in your cancer cells. Other important criteria include having good overall health and organ function. If you join the trial, you will receive the NK cell therapy and be closely monitored for any side effects and the effectiveness of the treatment. It’s important to note that there are several health conditions and recent treatments that could make you ineligible for this study, so discussing your medical history with the research team is essential.

Gender

ALL

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:
• • 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 6.Females of childbearing potential must have a negative serum pregnancy test. 7.Donor specific antibody (DSA) is negative: MFI \<= 2000. 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 recurence9. History of central nervous system disease or meningeal involvement such as epilepsy, paralysis, aphasia, stroke, etc
• • Active autoimmune diseases.
• • Serious cardiovascular and cerebrovascular diseases:a. Severe heart rhythm or conduction abnormalities, corrected OT interval (OTc)\>480 ms:h, Aute coronay sndrome conestve heat faur. aortic disection-stroke. or other orade 3 or hioher ardiovasular and cerebrovascular events within 6 months orior to firstinfusiorC, New York Heart Association (NYHA) class l or above congestive heart failure or left ventricular eiection fraction (LVEF \<50% in olor Doppler echocardiography,d. Hypertension that cannot be controlled by drug.
• • Active pulmonary infection: Sp02 90%: Pulmonary embolism, chronic obstructive pulmonary disease, or interstitial lung disease
• • Uncontrolled bacterial, fungal, or viral infection.Known HlV infection, active Hepatitis B (HBV) or Hepatitis C (HCV) infection
• • Historv of substance abuse.
• • Toxicity induced by previous therapy not recovered to s grade 2(NCI-CTCAE 5.0).15. Large suraical treatment within 4 weeks prior to first infusion, not including diagnostic biopsy.16. Pregnant/breastfeeding women.17. nvestigator-assessed presence of any medical or social issue that are likely to interfere with study conduct or may cause increased risk to subiect