Acute Myeloid Leukemia
Conditions
Keywords
Unfit AML
Brief summary
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
DRUGMAX-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.
DRUGAzacitidine
Given by IV, 75 mg/m2
DRUGVenetoclax
100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter.
Sponsors
Maxinovel Pty., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a prospective, multicenter, phase Ⅱ study consisting of dose escalation and ex-pansion stages
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. Age ≥65 years, or 2. 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
1. AML with BCR::ABL1 fusion、Acute promyelocytic leukemia (APL). 2. Secondary AML, including:Therapy-related AML (per WHO classification)、AML with prior history of myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN). 3. Use of strong/moderate CYP3A4 inducers within 3 days prior to treatment initiation. 4. Hypersensitivity to any study drugs. 5. Active malignancy in other organs (requiring treatment). 6. 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) 7. Active infections, including:Untreated tuberculosis or any aspergillosis. 8. Known HIV, active hepatitis B (HBV), or hepatitis C (HCV). 9. Central nervous system (CNS) leukemia at baseline. 10. Conditions limiting oral drug absorption (e.g., malabsorption syndrome). 11. Medical history of:Epilepsy requiring medication、Dementia or psychiatric disorders impairing protocol compliance. 12. Investigator's discretion for ineligibility.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT | Dose escalation; an average of 6 months. | The dose limiting toxicities, Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 |
| Adverse events (AEs), serious adverse events (SAEs) | Through study completion; an average of 24 months. | Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 |
| Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) | Dose escalation; an average of 6 months. | Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 |
| CRc | Through study completion; an average of 24 months. | complete remission rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RFS | Through study completion; an average of 8 months. | Recurrence-Free Survival |
| DoR | Through study completion; an average of 8 months. | duration of response |
| OS | Through study completion; an average of 24 months. | overall survival |
Countries
China
Contacts
CONTACTJing Wang
PRINCIPAL_INVESTIGATORJianxiang Wang, MD
Institute of Institute of Hematology & Blood Diseases Hospital
Outcome results
None listed