Clinical trial · Interventional
Liposomal Mitoxantrone Plus Azacitidine and Venetoclax in Newly Diagnosed Elderly or Unfit AML
A Phase Ib Study of Liposomal Mitoxantrone Combined With Azacitidine and Venetoclax in Newly Diagnosed Elderly or Unfit Patients With Acute Myeloid Leukemia
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 19, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260919-000001
Summary
Brief summary (as posted)
This prospective, open-label, multicenter phase Ib trial will evaluate the safety, tolerability, and RP2D of the VAM regimen (liposomal mitoxantrone + azacitidine \[AZA\] + venetoclax \[VEN\]) in elderly or unfit patients with newly diagnosed AML. A standard 3+3 dose escalation will enroll 12-30 patients, testing liposomal mitoxantrone at 8, 12, 16, and 20 mg/m². VEN duration (9 vs. 14 days) will be determined at the 8 mg/m² dose level, after which only liposomal mitoxantrone will be escalated while AZA and VEN will remain fixed. Induction therapy will consist of up to two 28-day cycles. Responders achieving CR/CRi/MLFS will be eligible for up to 4 consolidation cycles (total ≤6 cycles), after which they will proceed to maintenance with either AZA+VEN or observation.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Myeloid Leukemia (AML) | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Azacitidine | Drug | Azacitidine | ALIAS |
| Liposome Mitoxantrone | Drug | — | UNRESOLVED |
| Venetoclax | Drug | Venetoclax | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Venetoclax, azacitidine combined with liposome mitoxantrone as induction regimen
- description
- The trial will employ a standard 3+3 dose escalation design, testing liposomal mitoxantrone at 8, 12, 16, and 20 mg/m². VEN duration (9 vs. 14 days) will be determined at the 8 mg/m² dose level, after which only liposomal mitoxantrone will be escalated while AZA and VEN will remain fixed. Venetoclax duration will be sequentially escalated (9 vs. 14 days), choosing the longest duration without dose-limiting toxicity (DLT) in 3-6 evaluable patients. The RP2D for liposomal mitoxantrone is the highest dose with ≤1 DLT in 6 patients; if DL4 is tolerated, RP2D = 20 mg/m² on day 1.
- interventionNames
- Drug: Liposome Mitoxantrone
- Drug: Venetoclax
- Drug: Azacitidine
Primary outcomes (3)
- measure
- Dose-Limiting Toxicity (DLT)
- timeFrame
- Cycle 1(up to 42 days)
- description
- To evaluate the safety, tolerability, and RP2D of the VAM regimen in newly diagnosed elderly/unfit AML patients.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 99 Years
Show eligibility criteria text
Inclusion Criteria:
* Subjects eligible for enrollment in this study must meet all of the following criteria:
1. Diagnosis of acute myeloid leukemia (AML) according to the WHO 2022 or ICC criteria, excluding acute promyelocytic leukemia (APL).
2. No prior therapy for AML, except hydroxyurea for the management of hyperleukocytosis.
3. Meeting at least one of the following criteria:
1. Age ≥ 75 years;
2. Age 18-74 years with at least one of the following conditions precluding suitability for intensive chemotherapy:
i. ECOG performance status 2-3; ii. Cardiac dysfunction with left ventricular ejection fraction (LVEF) ≤ 50%; iii. Pulmonary dysfunction with diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%; iv. Creatinine clearance 30-45 mL/min; v. Other major organ dysfunction or comorbidities that, in the investigator's judgment, render the patient unsuitable for intensive chemotherapy.
4. ECOG performance status 0-3.
5. Life expectancy ≥ 3 months.
6. Patients of childbearing potential agree to use effective contraception during the treatment period and for at least 6 months after the last dose of study treatment.
7. Voluntary written informed consent provided.
Exclusion Criteria:
* Subjects who meet any of the following criteria will not be eligible for enrollment in this study:
1. Acute promyelocytic leukemia (APL)..
2. Active central nervous system (CNS) leukemia.
3. Prior targeted therapy or chemotherapy for AML, excluding hydroxyurea.
4. Uncontrolled active infection.
5. Uncontrolled cardiovascular disease: New York Heart Association (NYHA) class III-IV heart failure, myocardial infarction or unstable angina within 6 months before enrollment, or uncontrolled hypertension.
6. Left ventricular ejection fraction (LVEF) \< 40%.
7. Concurrent active malignancy, except for cured non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer.
8. Known hypersensitivity to the study drugs or their excipients.
9. Pregnant or breastfeeding women.
10. Any other condition that, in the investigator's judgment, would make the patient unsuitable for study participation.References
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