Phase 1 Open-label Study of AMX-883 Alone in Participants With AML and High-risk MDS and in Combination in Participants With AML

Официальное название

A Phase 1, Open-Label, Multi-Centre Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of AMX-883 Monotherapy in Participants With Acute Myeloid Leukaemia and High-Risk Myelodysplastic Syndrome and in Combination With Anticancer Agents in Participants With Acute Myeloid Leukaemia

Обзор

The purpose of the study is to assess the safety, pharmacokinetics, and preliminary efficacy of AMX-883 monotherapy in participants with acute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome (MDS) and in combination with anticancer agents in participants with AML.

Подробное описание

This is a modular, Phase 1, open-label, multi-centre dose-escalation study investigating AMX-883 in participants with relapsed/refractory AML and high-risk MDS. The study comprises Module 1, which will evaluate AMX-883 as monotherapy and in combination with posaconazole.

Module 1 consists of three parts:

* Part A consists of the monotherapy dose escalation cohorts and investigation of the food-effect at selected dose(s). * Part B consists of AMX-883 in combination with posaconazole dose escalation cohorts.

Other modules may be added by protocol amendment. The study aims to establish optimal dosing and preliminary efficacy data to support further clinical development of AMX-883.

Вмешательства

• Препарат AMX-883
  AMX-883 will be administered orally.
• Препарат Posaconazole
  Posaconazole tablets will be administered orally.

Первичные конечные точки

• Number of participants with adverse events (AEs), treatment-emergent adverse events (TEAEs), adverse events of special interests (AESIs) and serious adverse events (SAEs) [Срок оценки: Until 30 days after last dose (Approximately 2 years 8 months)]
• Number of participants with dose limiting toxicities (DLTs) [Срок оценки: During Cycle 1 (each cycle will be 28 days)]

Вторичные конечные точки (12)

• Maximum plasma concentration (Cmax) [Срок оценки: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)]
• Minimum plasma concentration (Cmin) [Срок оценки: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)]
• Time to Cmax (Tmax) [Срок оценки: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)]
• Terminal plasma half-life (t½λz) [Срок оценки: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)]
• Area under the plasma concentration-time curve from zero to infinity (AUCinf) [Срок оценки: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)]
• Oral plasma clearance (CL/F) [Срок оценки: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)]
• Oral volume of distribution during terminal phase (Vz/F) [Срок оценки: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)]
• Mean residence time (MRT) [Срок оценки: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)]
• Area under the plasma concentration-time curve from zero to tau (AUC0-tau) where tau=12 [Срок оценки: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)]
• Composite complete remission (CRc) (AML) [Срок оценки: Approximately 2 years 8 months]
• Morphologic leukaemia-free state (MLFS) (AML) [Срок оценки: Approximately 2 years 8 months]
• Overall Response rate (ORR) (AML) [Срок оценки: Approximately 2 years 8 months]

Критерии участия

Критерии включения

• Participants with relapsed or refractory AML who have failed all available standard therapies or relapsed or refractory high-risk MDS with BM blasts 10-19%
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate washout from prior therapies
• Adequate kidney and liver function
• Female participants of childbearing potential must use highly effective contraception, and male participants must agree to use barrier contraception and avoid sperm donation for at least 120 days after last dose
• If enrolled in M1B: Participant must have no documented contraindication to treatment with posaconazole before start of treatment

Критерии исключения

• Diagnosis of acute promyelocytic leukaemia or chronic myelogenous leukaemia in blast crisis
• Clinically active central nervous system (CNS) leukaemia
• Receiving immunosuppressive therapy post HSCT
• History of another malignancy that is active, progressing, or has required systemic treatment within the past 2 years
• Presence of >Grade 1 active graft versus host disease within 4 weeks prior to C1D1
• Significant cardiovascular disease
• Family history of sudden cardiac death before 40 years of age or a family history of long QT syndrome
• Clinically significant electrolyte imbalances (e.g., hypokalaemia, hypomagnesaemia, hypocalcaemia) that may contribute to QT interval prolongation
• Clinically significant bradycardia (<50 beats per minute) that is symptomatic or causes haemodynamic instability
• Major surgery within 4 weeks prior to C1D1 or inadequate recovery from prior surgery
• Uncontrolled intercurrent illness
• Inability to fast, swallow, ingest, or absorb oral medication due to a pre-existing condition
• History of interstitial lung disease or pneumonitis requiring systemic corticosteroid treatment
• Requirement for medications with a known risk of Torsades de Pointes that cannot be discontinued prior to study treatment
• Detectable human immunodeficiency virus (HIV) viral load
• Known serologic status reflecting active hepatitis B or C infection
• Active uncontrolled systemic fungal, bacterial, viral, or other infection or a condition predisposing to severe infection

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07723703 · AMX-883-C001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗