Acute Myeloid LeukemiaPhase 2NCT06778187
Oral-ATO for TP53-mutated Myeloid Malignancies
A Phase 2 study testing Oral arsenic trioxide in people with Acute Myeloid Leukemia and Myelodysplastic Neoplasm, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
This is an open-label, phase 2 study of oral arsenic trioxide (Arsenol ®) in combination with ascorbic acid and investigator choice of low-intensity therapy in patients with previously untreated or relapse/refractory TP53-mutated acute myeloid leukemia (AML), myelodysplastic neoplasm (MDS), chronic myelomonocytic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Neoplasm, Chronic Myelomonocytic Leukemia
- What is being tested?
- Oral arsenic trioxide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteHong Kong
- Study dates
- 7 Feb 2025to Feb 2028
- Phase
- Phase 2
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
- Willing and able to provide informed consent
- Age ≥18 years
- Diagnosis of acute myeloid leukemia (AML), myelodysplastic neoplasm (MDS) or chronic myelonocytic leukaemia (CMML) by World Health Organization (WHO) 2022 criteria (1, 3)
- Presence of TP53 mutation
- Previously untreated patients for Cohort A (Treatment-naïve), or Patients failing 1 or more lines of prior treatment for Cohort B (Relapsed and Refractory)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
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- Women of childbearing potential and fertile men must agree to use an approved method of contraception from Screening until 30 days after the last dose of oral arsenic trioxide, ascorbic acid, venetoclax and azacitidine/decitabine/oral-decitabine-cedazuridine.
- Willing and able to provide informed consent
- Age ≥18 years
- Diagnosis of acute myeloid leukemia (AML), myelodysplastic neoplasm (MDS) or chronic myelonocytic leukaemia (CMML) by World Health Organization (WHO) 2022 criteria (1, 3)
- Presence of TP53 mutation
- Previously untreated patients for Cohort A (Treatment-naïve), or Patients failing 1 or more lines of prior treatment for Cohort B (Relapsed and Refractory)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Women of childbearing potential and fertile men must agree to use an approved method of contraception from Screening until 30 days after the last dose of oral arsenic trioxide, ascorbic acid, venetoclax and azacitidine/decitabine/oral-decitabine-cedazuridine.
Who cannot join
- Use of an investigational agent within 14 days of study treatment (or at least 7 half-lives of that agent, whichever is longer), prior to the first dose of oral arsenic trioxide
- Known hypersensitivity to arsenic trioxide, ascorbic acid, venetoclax or azacitidine/decitabine/oral-decitabine-cedazuridine or their excipients.
- Uncontrolled, active infection
- Major surgery within 4 weeks of starting the study drug, or not recovered from side effects of surgery
- Any other serious medical conditions that could compromise study participation, in the opinion of the investigator
- Known HIV infection or known, active hepatitis B or hepatitis C infection
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- Concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, i.e., non-melanoma skin cancers, are eligible)
- Known history of long QT syndrome (LQTS) or corrected QT interval by Fridericia formula (QTcF) ≥ 480 ms
- Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to hemolysis) as defined by any of the following local laboratory parameters:
- Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation or eGFR; using CKD-EPI) < 40 mL/min
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 x the local upper limit of normal
- Pregnant or lactating females, or females planning to become pregnant at any time during the study
- Unwilling or unable to comply with the study protocol
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hong Kong1 site, 1 recruiting
- Recruiting
Queen Mary Hospital, Hong Kong
Hong Kong
Harinder Gill, MD, +852 2255 5859, gillhsh@hku.hk
Harinder Gill
About this study
Official title: A Phase 2 Study of Oral Arsenic Trioxide (Arsenol ®)-Based Low-intensity Treatment for Previously Untreated or Relapsed/Refractory TP53-mutated Myeloid Malignancies
This is an open-label, phase 2 study of oral arsenic trioxide (Arsenol ®) in combination with ascorbic acid and investigator choice of low-intensity therapy in patients with previously untreated or relapse/refractory TP53-mutated acute myeloid leukemia (AML), myelodysplastic neoplasm (MDS), chronic myelomonocytic leukemia (CMML).
Read the detailed description
Approximately 30 patients will be enrolled prospectively. Approximately 15 patients will be previously untreated and 15 patients will be relapsed or refractory to 1 or more lines of therapy.
Oral arsenic trioxide (oral-ATO) (Arsenol ®) will be used in combination with ascorbic acid, and investigator choice of low-intensity therapy that comprised hypomethylating agent (HMA) with or without venetoclax. The choice of hypomethylating agents include subcutaneous (s.c.) / intravenous (i.v.) azacitidine, i.v. decitabine or oral-decitabine-cedazuridine. Patients will be treated in 28-day days cycles.
Pending study team review of the tolerability, hematologic response, and molecular response to the combination, a future randomized Phase 2 efficacy study may be planned.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Neoplasm, Chronic Myelomonocytic Leukemia, TP53 Gene Mutation, Arsenic Trioxide
- Being tested
- Oral arsenic trioxide
- Keywords
- Acute myeloid leukemia, Myelodysplastic neoplasm, Chronic myelomonocytic leukemia, TP53 mutation, Oral arsenic trioxide
- Medical subject headings
- Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral arsenic trioxideDrug
Patients will be treated in 28-day cycles.
Each cycles will comprise:
Oral arsenic trixoide (10mg/day or 0.15mg/kg/day in patients < 50kg) from Days 1-14
PLUS:
- Oral ascorbic acid (1000mg/day) from Days 1-14
- Azacitidine (75mg/m2/day s.c. or i.v.) from days 1-7; OR Decitabine (20mg/m2/day i.v.) from days 1-5; OR Oral-decitabine-cedazuridine (1 tablet/day) from days 1-5.
- Venetoclax (100mg-400mg/day) from Days 1-14 (if used)
| Study group | Role | What they receive |
|---|---|---|
| Oral arsenic trixoide | Experimental | Patients will be treated in 28-day cycles.
Each cycles will comprise:
Oral ATO (10mg/day or 0.15mg/kg/day in patients < 50kg) from Days 1-14
PLUS:
* Oral ascorbic acid (1000mg/day) from Days 1-14
* Azacitidine (75mg/m2/day s.c. or i.v.) from days 1-7; OR Decitabine (20mg/m2/day i.v.) from days 1-5; OR Oral-decitabine-cedazuridine (1 tablet/day) from days 1-5.
* Venetoclax (100mg-400mg/day) from Days 1-14 (if used) Receives: Drug: Oral arsenic trioxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Enumeration and description of adverse events (AEs), serious adverse events (SAEs), and other AEs
Measured: 24 months
Secondary outcomes (2)
Response rates
Proportion of patients who achieve a response by European LeukemiaNet (ELN) criteria (for AML) and International Working Group (IWG) criteria (for MDS and CMML)
Measured: 24 months
Rates of molecular responses
Changes in mutant allele frequencies of TP53 mutations and other co-mutations during treatment
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2025
- Study start7 Feb 2025
- Primary completionFeb 2027 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Harinder Gill, MD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06778187
- Sponsor's protocol ID
- ATO-IIS001
- Status last verified
- Jan 2025
- First submitted
- 10 Jan 2025
- Last updated
- 10 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared due to confidentiality issues.
Publications
Sallman DA, Stahl M. TP53-mutated acute myeloid leukemia: how can we improve outcomes? Blood. 2025 Jun 12;145(24):2828-2833. doi: 10.1182/blood.2024024245.
PubMed 39236289