Oral arsenic trioxide plus vitamin C with low-intensity therapy for TP53-mutated AML/MDS/CMML

A Phase 2 Study of Oral Arsenic Trioxide (Arsenol ®)-Based Low-intensity Treatment for Previously Untreated or Relapsed/Refractory TP53-mutated Myeloid Malignancies

This trial will test whether taking oral arsenic trioxide with vitamin C plus a low-intensity drug (a hypomethylating agent, with or without venetoclax) helps adults with TP53-mutated AML, MDS, or CMML who are newly diagnosed or have relapsed/refractory disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The University of Hong Kong (Academic / other)
• Locations: 1 site (Hong Kong)
• Trial ID: NCT06778187 on ClinicalTrials.gov

What this trial studies

This open-label Phase 2 study plans to enroll about 30 adults with TP53-mutated acute myeloid leukemia, myelodysplastic neoplasm, or chronic myelomonocytic leukemia, split roughly between treatment-naïve and relapsed/refractory cohorts. Participants will receive oral arsenic trioxide (Arsenol®) together with ascorbic acid and an investigator-selected low-intensity therapy—typically a hypomethylating agent given with or without venetoclax—on 28-day cycles. The study will monitor tolerability, hematologic responses, and molecular responses as primary signals of activity and safety. Pending tolerability and signal of benefit, investigators may plan a future randomized Phase 2 efficacy study.

Who should consider this trial

Good fit: Adults (≥18) with AML, MDS, or CMML who have a confirmed TP53 mutation and are either treatment-naïve or have failed one or more prior therapies, with ECOG performance status 0–2, are the intended candidates.

Not a fit: Patients without a TP53 mutation, those with ECOG >2, pregnant people, or those unable to travel to the single study site are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, this oral combination could improve response rates and offer a more convenient, lower-intensity treatment option for patients with TP53-mutated myeloid malignancies.

How similar studies have performed: Arsenic trioxide is highly effective in acute promyelocytic leukemia, but using oral ATO plus vitamin C with hypomethylating agents for TP53-mutated myeloid diseases is largely experimental with only limited early data.

Eligibility 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:

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

Where this trial is running

Hong Kong

• Queen Mary Hospital, Hong Kong — Hong Kong, Hong Kong (Recruiting)

Study contacts

• Principal investigator: Harinder Gill, MD — The University of Hong Kong
• Study coordinator: Harinder Gill, MD

Conditions Acute Myeloid Leukemia; Myelodysplastic Neoplasm; Chronic Myelomonocytic Leukemia; TP53 Gene Mutation; Arsenic Trioxide; Acute myeloid leukemia; Myelodysplastic neoplasm; Chronic myelomonocytic leukemia