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Liposomal Mitoxantrone Plus Azacitidine and Venetoclax in Newly Diagnosed Elderly or Unfit AML

15 september 2026 uppdaterad av: Institute of Hematology & Blood Diseases Hospital, China

A Phase Ib Study of Liposomal Mitoxantrone Combined With Azacitidine and Venetoclax in Newly Diagnosed Elderly or Unfit Patients With Acute Myeloid Leukemia

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.

Studieöversikt

Status

Har inte rekryterat ännu

Betingelser

Intervention / Behandling

Studietyp

Interventionell

Inskrivning (Beräknad)

30

Fas

  • Fas 1

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

  • Vuxen
  • Äldre vuxen

Tar emot friska volontärer

Nej

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Venetoclax, azacitidine combined with liposome mitoxantrone as induction regimen

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.
Läkemedel: Liposome Mitoxantrone
Liposome Mitoxantrone: 8, 12, 16, and 20 mg/m², administered by intravenous drip (ivgtt) on day 1, every 4 weeks
Läkemedel: Venetoclax
Venetoclax(9 days): 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-9, administered orally (po), every 4 weeks Venetoclax(14 days): 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14, administered orally (po), every 4 weeks
Läkemedel: Azacitidine
Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7, every 4 weeks

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Dose-Limiting Toxicity (DLT)
Tidsram: Cycle 1(up to 42 days)
To evaluate the safety, tolerability, and RP2D of the VAM regimen in newly diagnosed elderly/unfit AML patients.
Cycle 1(up to 42 days)
Incidence of treatment-related adverse events
Tidsram: From day 1 of treatment to 28 days after the last dose
The safety of the drug was evaluated by NCI-CTC AE 5.0 standard which including hematologic and non-hematologic toxicity
From day 1 of treatment to 28 days after the last dose
Composite complete remission (CRc) rate
Tidsram: Up to approximately eight weeks
Proportion of patients with complete remission (CR), complete remission with incomplete hematologic recovery (CRi) or morphologic leukemia-free state (MLFS)
Up to approximately eight weeks

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Complete remission (CR) rate
Tidsram: Up to approximately eight weeks
Proportion of patients with complete remission (CR)
Up to approximately eight weeks
Complete remission with incomplete hematologic recovery (CRi) rate
Tidsram: Up to approximately eight weeks
Proportion of patients with complete remission with incomplete hematologic recovery (CRi)
Up to approximately eight weeks
Morphologic leukemia-free state (MLFS) rate
Tidsram: Up to approximately eight weeks
Proportion of patients with morphologic leukemia-free state (MLFS)
Up to approximately eight weeks
Event-free survival (EFS)
Tidsram: Up to approximately 5 years
It is defined as the time from the start of study treatment to the occurrence of induction failure or disease progression or death from any cause (whichever occurs first)
Up to approximately 5 years
Overall survival (OS)
Tidsram: Up to approximately 5 years
It is defined as the time from the start of study treatment to the death from any cause
Up to approximately 5 years
Relapse-free Survival (RFS)
Tidsram: Up to approximately 5 years
It is defined as the time from the start of achieving remission to disease progression, death from any cause or the last follow-up
Up to approximately 5 years
Duration of Response (DoR)
Tidsram: Up to approximately 5 years
It is defined as the time from the first documentation of CRc to relapse
Up to approximately 5 years
30-day postinduction mortality
Tidsram: Up to approximately 30 days
It is defined as death from any cause within 30 days after the start of induction
Up to approximately 30 days
60-day postinduction mortality
Tidsram: Up to approximately 60 days
t is defined as death from any cause within 60 days after the start of induction
Up to approximately 60 days
Measurable Residual Disease (MRD) negative rate by flow cytometry
Tidsram: Up to approximately eight weeks
Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative by flow cytometry
Up to approximately eight weeks
Measurable Residual Disease (MRD) negative rate by molecular testing
Tidsram: Up to approximately eight weeks
Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative by molecular testing
Up to approximately eight weeks

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Beräknad)

30 oktober 2026

Primärt slutförande (Beräknad)

31 december 2027

Avslutad studie (Beräknad)

31 december 2032

Studieregistreringsdatum

Först inskickad

15 september 2026

Först inskickad som uppfyllde QC-kriterierna

15 september 2026

Första postat (Faktisk)

18 september 2026

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

18 september 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

15 september 2026

Senast verifierad

1 augusti 2026

Mer information

Termer relaterade till denna studie

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • IIT2026104

Plan för individuella deltagardata (IPD)

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NEJ

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