Oral-ATO for TP53-mutated Myeloid Malignancies

June 5, 2025 updated by: The University of Hong Kong

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Harinder Gill, MD
  • Phone Number: +852 2255 5859
  • Email: gillhsh@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Queen Mary Hospital, Hong Kong
        • Principal Investigator:
          • Harinder Gill, MD
        • Contact:
          • Harinder Gill, MD
          • Phone Number: +852 2255 5859
          • Email: gillhsh@hku.hk
        • Contact:
          • Harinder Gill

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Willing and able to provide informed consent
  2. Age ≥18 years
  3. Diagnosis of acute myeloid leukemia (AML), myelodysplastic neoplasm (MDS) or chronic myelonocytic leukaemia (CMML) by World Health Organization (WHO) 2022 criteria (1, 3)
  4. Presence of TP53 mutation
  5. Previously untreated patients for Cohort A (Treatment-naïve), or Patients failing 1 or more lines of prior treatment for Cohort B (Relapsed and Refractory)
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  7. 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.

Exclusion Criteria:

Inclusion Criteria

  1. Willing and able to provide informed consent
  2. Age ≥18 years
  3. Diagnosis of acute myeloid leukemia (AML), myelodysplastic neoplasm (MDS) or chronic myelonocytic leukaemia (CMML) by World Health Organization (WHO) 2022 criteria (1, 3)
  4. Presence of TP53 mutation
  5. Previously untreated patients for Cohort A (Treatment-naïve), or Patients failing 1 or more lines of prior treatment for Cohort B (Relapsed and Refractory)
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  7. 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.

Exclusion Criteria

  1. 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
  2. Known hypersensitivity to arsenic trioxide, ascorbic acid, venetoclax or azacitidine/decitabine/oral-decitabine-cedazuridine or their excipients.
  3. Uncontrolled, active infection
  4. Major surgery within 4 weeks of starting the study drug, or not recovered from side effects of surgery
  5. Any other serious medical conditions that could compromise study participation, in the opinion of the investigator
  6. Known HIV infection or known, active hepatitis B or hepatitis C infection
  7. Concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, i.e., non-melanoma skin cancers, are eligible)
  8. Known history of long QT syndrome (LQTS) or corrected QT interval by Fridericia formula (QTcF) ≥ 480 ms

  9. 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:

    1. Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation or eGFR; using CKD-EPI) < 40 mL/min
    2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 x the local upper limit of normal
  10. Pregnant or lactating females, or females planning to become pregnant at any time during the study
  11. Unwilling or unable to comply with the study protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral arsenic trixoide

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)
Drug: Oral arsenic trioxide

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: 24 months
Enumeration and description of adverse events (AEs), serious adverse events (SAEs), and other AEs
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rates
Time Frame: 24 months
Proportion of patients who achieve a response by European LeukemiaNet (ELN) criteria (for AML) and International Working Group (IWG) criteria (for MDS and CMML)
24 months
Rates of molecular responses
Time Frame: 24 months
Changes in mutant allele frequencies of TP53 mutations and other co-mutations during treatment
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Investigators

  • Principal Investigator: Harinder Gill, MD, The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2025

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

February 1, 2028

Study Registration Dates

First Submitted

January 10, 2025

First Submitted That Met QC Criteria

January 10, 2025

First Posted (Actual)

January 16, 2025

Study Record Updates

Last Update Posted (Actual)

June 10, 2025

Last Update Submitted That Met QC Criteria

June 5, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ATO-IIS001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared due to confidentiality issues.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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