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

15 septembre 2026 mis à jour par: 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.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Estimé)

30

Phase

  • La phase 1

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: Liposome Mitoxantrone
Liposome Mitoxantrone: 8, 12, 16, and 20 mg/m², administered by intravenous drip (ivgtt) on day 1, every 4 weeks
Médicament: 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
Médicament: Azacitidine
Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7, every 4 weeks

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Dose-Limiting Toxicity (DLT)
Délai: 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
Délai: 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
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Complete remission (CR) rate
Délai: 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
Délai: 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
Délai: Up to approximately eight weeks
Proportion of patients with morphologic leukemia-free state (MLFS)
Up to approximately eight weeks
Event-free survival (EFS)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Institute of Hematology & Blood Diseases Hospital, China

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

30 octobre 2026

Achèvement primaire (Estimé)

31 décembre 2027

Achèvement de l'étude (Estimé)

31 décembre 2032

Dates d'inscription aux études

Première soumission

15 septembre 2026

Première soumission répondant aux critères de contrôle qualité

15 septembre 2026

Première publication (Réel)

18 septembre 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

18 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

15 septembre 2026

Dernière vérification

1 août 2026

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • IIT2026104

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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