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

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

Eligibility

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

Conditions2

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