NK cell therapy targeting specific markers in acute myeloid leukemia

Clinical Study to Evaluate the Safety and Efficacy of iPSC -NK Cells Targeting CLL1 or CD33 in Patients With Relapsed/Refractory AML

This study is testing a new type of immune cell therapy for people with relapsed or hard-to-treat acute myeloid leukemia to see if it can help them feel better and improve their treatment outcomes.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Zhejiang University (Academic / other)
• Drugs / interventions: CAR-T, Chimeric antigen receptor
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06367673 on ClinicalTrials.gov

What this trial studies

This phase 1, first-in-human study evaluates the safety, tolerability, and preliminary efficacy of Chimeric Antigen Receptor (CAR) engineered natural killer (NK) cells derived from induced pluripotent stem cells, specifically targeting CLL1 or CD33 in patients with relapsed or refractory acute myeloid leukemia (AML). The study aims to leverage the high expression of these targets in AML cells while sparing normal hematopoietic stem cells, potentially improving treatment outcomes for this challenging condition. Participants will receive NK cell infusions and will be monitored for safety and effectiveness.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed relapsed or refractory AML expressing CLL1 or CD33.

Not a fit: Patients who are allergic to the study drug or have received prior antitumor therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a novel and effective treatment option for patients with relapsed or refractory AML.

How similar studies have performed: Other studies targeting similar markers in AML have shown promise, indicating a potential for success in this approach.

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

Where this trial is running

Hangzhou, Zhejiang

• the First Affiliated Hospital, School of Medicine, Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: He Huang, MD — First Affiliated Hospital of Zhejiang University
• Study coordinator: He Huang, MD

Conditions AML, Adult; AML