Acute Myeloid Leukemia, Arsenic Trioxide, Chronic Myelomonocytic Leukemia, Myelodysplastic Neoplasm, TP53 Gene Mutation
Conditions
Keywords
Acute myeloid leukemia, Myelodysplastic neoplasm, Chronic myelomonocytic leukemia, TP53 mutation, Oral arsenic trioxide
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).
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.
Interventions
DRUGOral 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)
Sponsors
The University of Hong Kong
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 24 months | Enumeration and description of adverse events (AEs), serious adverse events (SAEs), and other AEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response rates | 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) |
| Rates of molecular responses | 24 months | Changes in mutant allele frequencies of TP53 mutations and other co-mutations during treatment |
Countries
Hong Kong
Contacts
Primary ContactHarinder Gill, MD
Outcome results
None listed