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NCT Number: NCT07723703

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

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.

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Key information

Conditions

Acute Myeloid Leukaemia Hematologic Diseases Hemic and Lymphatic Diseases High Risk Myelodysplastic Syndrome Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

AMX-883

Drug

AMX-883 will be administered orally.

Posaconazole

Drug

Posaconazole tablets will be administered orally.

Primary outcomes

  1. Number of participants with adverse events (AEs), treatment-emergent adverse events (TEAEs), adverse events of special interests (AESIs) and serious adverse events (SAEs)

    Time frame: Until 30 days after last dose (Approximately 2 years 8 months)

    To determine the safety and tolerability of AMX-883 in participants with relapsed or refractory AML and high-risk MDS when administered as monotherapy and in combination with posaconazole.

  2. Number of participants with dose limiting toxicities (DLTs)

    Time frame: During Cycle 1 (each cycle will be 28 days)

    To determine the maximum tolerated dose (MTD)/optimal biological dose (OBD) and the recommended dose for expansion (RDE) of AMX-883 in participants with relapsed or refractory AML and high-risk MDS when administered as monotherapy and in combination with posaconazole.

Secondary outcomes

  1. Maximum plasma concentration (Cmax)

    Time frame: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

    To characterise the PK (Cmax) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (Cmax) of AMX-883.

  2. Minimum plasma concentration (Cmin)

    Time frame: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

    To characterise the PK (Cmin) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (Cmin) of AMX-883.

  3. Time to Cmax (Tmax)

    Time frame: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

    To characterise the PK (Tmax) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (Tmax) of AMX-883.

  4. Terminal plasma half-life (t½λz)

    Time frame: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

    To characterise the PK (t½λz) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (t½λz) of AMX-883.

  5. Area under the plasma concentration-time curve from zero to infinity (AUCinf)

    Time frame: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

    To characterise the PK (AUCinf) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (AUCinf) of AMX-883.

  6. Oral plasma clearance (CL/F)

    Time frame: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

    To characterise the PK (CL/F) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (CL/F) of AMX-883.

  7. Oral volume of distribution during terminal phase (Vz/F)

    Time frame: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

    To characterise the PK (Vz/F) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (Vz/F) of AMX-883.

  8. Mean residence time (MRT)

    Time frame: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

    To characterise the PK (MRT) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (MRT) of AMX-883.

  9. Area under the plasma concentration-time curve from zero to tau (AUC0-tau) where tau=12

    Time frame: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

    To characterise the PK (AUC0-tau) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (AUC0-tau) of AMX-883. AUC at other timepoints may also be derived.

  10. Composite complete remission (CRc) (AML)

    Time frame: Approximately 2 years 8 months

    CRc is defined as percentage of participants with Complete remission (CR) and complete remission with partial haematologic recovery (CRh) and complete remission with incomplete count recovery (CRi). This will be used to explore early evidence of antileukaemic activity (ALA) of AMX-883 when administered as monotherapy and in combination with posaconazole in participants.

  11. Morphologic leukaemia-free state (MLFS) (AML)

    Time frame: Approximately 2 years 8 months

    MLFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.

  12. Overall Response rate (ORR) (AML)

    Time frame: Approximately 2 years 8 months

    ORR is defined as CR, CRh, or CRi with or without MRD. ORR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.

  13. Duration of remission (DOR) (AML)

    Time frame: Approximately 2 years 8 months

    DOR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.

  14. Transfusion independence (TI) (AML)

    Time frame: Approximately 2 years 8 months

    TI will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.

  15. Relapse-free survival (RFS) (AML)

    Time frame: Approximately 2 years 8 months

    RFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.

  16. Progression-free survival (PFS) (AML)

    Time frame: Approximately 2 years 8 months

    PFS is defined as the time from the first dose until which participants can continue receiving treatment without experience any progressive disease. PFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.

  17. Event-free survival (EFS) (AML)

    Time frame: Approximately 2 years 8 months

    EFS is defined as the failure to achieve CR. EFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.

  18. Time to response (TTR) (AML)

    Time frame: Approximately 2 years 8 months

    TTR is defined as the time taken to achieve CR, ORR and CRc after starting the treatment. TTR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.

  19. Overall survival (OS) (AML)

    Time frame: Approximately 2 years 8 months

    OS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.

  20. Treatment failure (AML)

    Time frame: Approximately 2 years 8 months

    Treatment failure will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.

  21. 30-day and 60-day mortality rate (Extramedullary Disease- 30 [ED-30] and ED-60) (AML)

    Time frame: Approximately 2 years 8 months

    ED-30 and ED-60 will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.

  22. CR (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    CR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  23. CR equivalent (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    CR equivalent will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  24. Partial remission (PR) (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    PR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  25. Complete remission with limited count recovery (CRL) (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    CRL will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  26. CRh (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    CRh will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  27. Haematologic improvement (HI) (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    HI will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  28. ORR (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    ORR is defined by CR (or CR equivalent) + PR + CRL + CRh + HI. ORR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  29. DOR (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    DOR is defined as CR (or CR equivalent) + PR + CRL + CRh + HI. DOR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  30. TTR (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    TTR is defined as the time from first dose of study treatment to the first documented evidence of achieving a CR, ORR and CRc.

    TTR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  31. PFS (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    PFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  32. EFS (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    EFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  33. OS (high-risk MDS)

    Time frame: Approximately 2 years 8 months

    OS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.

  34. Change from baseline in BRD9 expression levels in peripheral blood mononuclear cells (PBMCs)

    Time frame: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

    To investigate biomarkers potentially related to AMX-883 activity when administered as monotherapy and in combination with posaconazole.

Sponsors and collaborators

Lead sponsor

Amphista Therapeutics Ltd

Industry

Registry information

Official study title

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

Acronym: BRAMLIE

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
Jul 23, 2026
Registry last updated
Jul 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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