A Phase 2 Study of MAX-40279 Combined With Venetoclax and Azacitidine in Unfit Newly Diagnosed Acute Myeloid Leukemia

Overview

This is a prospective, multicenter, phase Ⅱ study consisting of dose escalation and ex-pansion stages in unfit newly diagnosed AML.

Detailed description

This is a prospective, multicenter, phase Ⅱ study consisting of dose escalation and ex-pansion stages in unfit newly diagnosed AML. Patients in dose escalation stage received oral MAX-40279 at three doses, in combination with VEN and AZA in 28-day cycles. Three to six patients were enrolled at each dose level. The dose limiting toxicities (DLTs) observation period was 28 days after the first dose. All evaluable patients with ≥1 cycle treatment were included in preliminary efficacy analysis.

Interventions

• Drug MAX-40279
  Dose escalation：MAX-40279: 40 mg, 50 mg, and 60 mg twice daily (BID). Dose expantion: MAX-40279 RP2D. Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter. Azacitidine: 75 mg/m2 days 1-7. 28 days are one cycle.
• Drug Azacitidine
  Given by IV, 75 mg/m2
• Drug Venetoclax
  100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter.

Primary outcome measures

• DLT [Time frame: Dose escalation; an average of 6 months.]
• Adverse events (AEs), serious adverse events (SAEs) [Time frame: Through study completion; an average of 24 months.]
• Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) [Time frame: Dose escalation; an average of 6 months.]
• CRc [Time frame: Through study completion; an average of 24 months.]

Secondary outcome measures (3)

• RFS [Time frame: Through study completion; an average of 8 months.]
• DoR [Time frame: Through study completion; an average of 8 months.]
• OS [Time frame: Through study completion; an average of 24 months.]

Eligibility criteria

Inclusion criteria

1\. Patients meeting the World Health Organization (WHO) 2016 diagnostic criteria for newly diagnosed acute myeloid leukemia (AML) patients unfit for intensive chemotherapy:

• Age ≥65 years, or
• Age >18 years and ineligible for standard-dose chemotherapy, defined by ≥1 of the following:

ECOG performance status 2 or 3；History of chronic heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) ≤50% DLCO ≤65% or FEV1 ≤65%Creatinine clearance ≥30 mL/min but ≤45 mL/min (Cockcroft-Gault)、Any other condition deemed incompatible with standard chemotherapy (requires PI approval) 2. No prior AML therapy, except:Hydroxyurea. 3. ECOG performance status ≤3 4. Laboratory requirements: WBC≤3×10\*9/L、AST/ALT/ALP ≤3×ULN (except: due to leukemic involvement)、Total bilirubin ≤1.5×ULN、Serum creatinine clearance ≥30 mL/min (measured or calculated) 5. Life expectancy ≥3 months 6. Contraception requirements: Negative pregnancy test for women of childbearing potential；Agreement to use effective contraception during treatment and for 6 months after therapy

Exclusion criteria

• AML with BCR::ABL1 fusion、Acute promyelocytic leukemia (APL).
• Secondary AML, including:Therapy-related AML (per WHO classification)、AML with prior history of myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN).
• Use of strong/moderate CYP3A4 inducers within 3 days prior to treatment initiation.
• Hypersensitivity to any study drugs.
• Active malignancy in other organs (requiring treatment).
• Active cardiac disease, defined as ≥1 of the following:Myocardial infarction within 6 months before enrollment；History of symptomatic arrhythmia requiring medication；Uncontrolled/symptomatic congestive heart failure (NYHA Class >2)
• Active infections, including:Untreated tuberculosis or any aspergillosis.
• Known HIV, active hepatitis B (HBV), or hepatitis C (HCV).
• Central nervous system (CNS) leukemia at baseline.
• Conditions limiting oral drug absorption (e.g., malabsorption syndrome).
• Medical history of:Epilepsy requiring medication、Dementia or psychiatric disorders impairing protocol compliance.
• Investigator's discretion for ineligibility.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Institute of Institute of Hematology & Blood Diseases Hospital ( Chinese Academy of Medica — Tianjin

Identifiers

NCT: NCT07743112 · MAX-40279-010 · CTR20250827

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• NMPA/CDE CTR20250827 (chinadrugtrials.org.cn platform)

View this study on ClinicalTrials.gov ↗