Acute Myeloid LeukaemiaPhase 1BRAMLIENCT07723703
Phase 1 Open-label Study of AMX-883 Alone in Participants With AML and High-risk MDS and in Combination in Participants With AML
A Phase 1 study testing AMX-883 and Posaconazole in people with Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome, run by Amphista Therapeutics Ltd at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukaemia, High Risk Myelodysplastic Syndrome
- What is being tested?
- AMX-883 and Posaconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Sep 2026to 30 Apr 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Amphista Medical Monitor contact
United States1 site, 1 recruiting
- Recruiting
NEXT Oncology Virginia
Fairfax, Virginia, 22031
About this study
Official 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
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.
Read the 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.
- Being tested
- AMX-883, Posaconazole
- Keywords
- Pharmacokinetics, Dose escalation, Bayesian Optimal INterval (BoIN), Bromodomain-Containing Protein 9 (BRD9), Monotherapy
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMX-883Drug
AMX-883 will be administered orally.
PosaconazoleDrug
Posaconazole tablets will be administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Module 1 Part A (M1A): AMX-883 monotherapy dose escalation cohort | Experimental | Participants will receive escalating dose levels of AMX-883 administered as monotherapy. Receives: Drug: AMX-883 |
| Module 1 Part A (M1A): AMX-883 monotherapy food effect cohort | Experimental | Participants will receive a selected dose of AMX-883 from the M1A dose escalation cohort, administered as monotherapy, under fed and fasted conditions. Receives: Drug: AMX-883 |
| Module 1 Part B (M1B): AMX-883 + posaconazole | Experimental | 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. Receives: Drug: AMX-883; Drug: Posaconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events (AEs), treatment-emergent adverse events (TEAEs), adverse events of special interests (AESIs) and serious adverse events (SAEs)
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.
Measured: Until 30 days after last dose (Approximately 2 years 8 months)
Number of participants with dose limiting toxicities (DLTs)
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.
Measured: During Cycle 1 (each cycle will be 28 days)
Secondary outcomes (34)
Maximum plasma concentration (Cmax)
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.
Measured: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Minimum plasma concentration (Cmin)
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.
Measured: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Time to Cmax (Tmax)
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.
Measured: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Terminal plasma half-life (t½λz)
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.
Measured: 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)
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.
Measured: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Oral plasma clearance (CL/F)
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.
Measured: 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)
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.
Measured: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Mean residence time (MRT)
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.
Measured: 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
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.
Measured: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Composite complete remission (CRc) (AML)
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.
Measured: Approximately 2 years 8 months
Morphologic leukaemia-free state (MLFS) (AML)
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.
Measured: Approximately 2 years 8 months
Overall Response rate (ORR) (AML)
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.
Measured: Approximately 2 years 8 months
Duration of remission (DOR) (AML)
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.
Measured: Approximately 2 years 8 months
Transfusion independence (TI) (AML)
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.
Measured: Approximately 2 years 8 months
Relapse-free survival (RFS) (AML)
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.
Measured: Approximately 2 years 8 months
Progression-free survival (PFS) (AML)
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.
Measured: Approximately 2 years 8 months
Event-free survival (EFS) (AML)
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.
Measured: Approximately 2 years 8 months
Time to response (TTR) (AML)
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.
Measured: Approximately 2 years 8 months
Overall survival (OS) (AML)
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.
Measured: Approximately 2 years 8 months
Treatment failure (AML)
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.
Measured: Approximately 2 years 8 months
30-day and 60-day mortality rate (Extramedullary Disease- 30 [ED-30] and ED-60) (AML)
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.
Measured: Approximately 2 years 8 months
CR (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
CR equivalent (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
Partial remission (PR) (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
Complete remission with limited count recovery (CRL) (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
CRh (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
Haematologic improvement (HI) (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
ORR (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
DOR (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
TTR (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
PFS (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
EFS (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
OS (high-risk MDS)
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.
Measured: Approximately 2 years 8 months
Change from baseline in BRD9 expression levels in peripheral blood mononuclear cells (PBMCs)
To investigate biomarkers potentially related to AMX-883 activity when administered as monotherapy and in combination with posaconazole.
Measured: At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2026
- Study start16 Sep 2026
- Primary completion4 Dec 2028 (estimated)
- Study completion30 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukaemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amphista Therapeutics Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07723703
- Sponsor's protocol ID
- AMX-883-C001
- Acronym
- BRAMLIE
- Status last verified
- Oct 2026
- First submitted
- 20 Jul 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: IPD information will not be shared due to legal/proprietary restrictions.