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

Purpose

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.

Conditions

  • Acute Myeloid Leukaemia
  • High Risk Myelodysplastic Syndrome

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Module 1 Part A (M1A): AMX-883 monotherapy dose escalation cohort 		Participants will receive escalating dose levels of AMX-883 administered as monotherapy.
  • Drug: AMX-883
    AMX-883 will be administered orally.
Experimental
Module 1 Part A (M1A): AMX-883 monotherapy food effect cohort 		Participants will receive a selected dose of AMX-883 from the M1A dose escalation cohort, administered as monotherapy, under fed and fasted conditions.
  • Drug: AMX-883
    AMX-883 will be administered orally.
Experimental
Module 1 Part B (M1B): AMX-883 + posaconazole 		Participants will receive a selected dose level for at least two escalating dose levels of AMX-883 selected from the M1A dose escalation cohort, administered in combination with posaconazole.
  • Drug: AMX-883
    AMX-883 will be administered orally.
  • Drug: Posaconazole
    Posaconazole tablets will be administered orally.

Recruiting Locations

NEXT Oncology Virginia
Fairfax, Virginia 22031

More Details

Status
Recruiting
Sponsor
Amphista Therapeutics Ltd

Study Contact

Amphista Medical Monitor
mm@amphista.com

Detailed Description

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.