AMX-883 in AML and high-risk MDS: a first-in-class dosing study

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a Phase 1, open-label, multi-center dose-escalation study of AMX-883 in adults with relapsed or refractory AML and high-risk MDS. It has a monotherapy module to determine safe dosing and a combination module with posaconazole to explore potential interactions and efficacy signals. Parts A and B evaluate escalating doses, safety, pharmacokinetics, and preliminary efficacy, aiming to establish dosing guidelines for future trials. The study will also assess food effects on AMX-883 and collect early signals of activity. Additional modules may be added as the protocol evolves.

Why it matters

Who can join: the full rules

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 for at least 120 days, or 27 weeks (applicable to the United Kingdom \[UK\] only), after last dose, 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 (applicable to rest of the world)
* Known history of human immunodeficiency virus (HIV)-1/2 antibodies with an HIV ribonucleic acid (RNA) viral load ≥50 copies/mL, cluster of differentiation (CD)4+ lymphocyte count \<350 cells/µL, a history of an acquired immunodeficiency syndrome-defining opportunistic infection within the past 12 months, on the same anti-HIV medications for \<12 weeks or further changes in the number or type of antiretroviral drugs in the regimen could be anticipated in the next 12 weeks (applicable to UK only)
* 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

Where it's running

• Memorial Sloan-Kettering Cancer Center - Hematology Service MSKCC
  New York, New York, United States Recruiting
• NEXT Oncology Virginia
  Fairfax, Virginia, United States Recruiting
• The Christie NHS Foundation Trust - Christie Hospital
  Manchester, Greater Manchester, United Kingdom Recruiting

Study contacts

• Study coordinator: Amphista Medical Monitor
• Email: mm@amphista.com

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.