Oral-ATO for TP53-mutated Myeloid Malignancies

NCT06778187 | Recruiting Phase 2 DMC

• 1 other identifier: ATO-IIS001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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 leukemia (CMML).

Conditions

Acute Myeloid Leukemia; Myelodysplastic Neoplasm; Chronic Myelomonocytic Leukemia; TP53 Gene Mutation; Arsenic Trioxide

Keywords

Acute myeloid leukemia; Myelodysplastic neoplasm; Chronic myelomonocytic leukemia; TP53 mutation; Oral arsenic trioxide

Outcome Measures

Primary Outcomes (1)

• Adverse events

  Enumeration and description of adverse events (AEs), serious adverse events (SAEs), and other AEs

  24 months

Secondary Outcomes (2)

• Response rates

  24 months

• Rates of molecular responses

  24 months

Study Arms (1)

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)

Drug: Oral arsenic trioxide

Interventions

Oral arsenic trioxide DRUG

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)

Oral arsenic trixoide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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
• 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

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Queen Mary Hospital, Hong Kong

Hong Kong, Hong Kong

RECRUITING

Related Publications (1)

• 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.

  PMID: 39236289 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts; Leukemia, Myelomonocytic, Chronic

Interventions

Arsenic Trioxide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds

Study Officials

• Harinder Gill, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Harinder Gill, MD

CONTACT

+852 2255 5859; gillhsh@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2025
• First Posted: January 16, 2025
• Study Start: February 7, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: June 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)