NPMc+ AML
Conditions
Keywords
NPM1 mutation, Acute myeloid leukemia, Oral arsenic trioxide
Brief summary
A prospective open-label phase 2 study will be designed to assess the efficacy of oral arsenic trioxide plus azacitidine in preventing relapses in patients with NPM1-mutant AML. After screening and eligibility assessment, patients will receive treatment with oral arsenic trioxide plus azacitidine for 12 months. The recruitment period will last for 24 months and it will take approximately 36 months for study completion.
Detailed description
Eligible subjects with NPM1 MRD positivity will receive oral arsenic trioxide (oral-As2O3) (Arsenol ®) (5-10mg per day, from days 1-7 per cycle), ascorbic acid (1g per day, from days 1 - 7 per cycle) plus azacitidine (75mg/m2 per day subcutaneously, from days 1 to 3 per cycle). Each cycle of oral-As2O3 plus azacitidine will be given once every 28 days. The total duration of treatment is 12 months (12 cycles). Treatment will be day-care and outpatient based. Reduction in the dosage and duration of oral-As2O3 is required if the subject is experiencing adverse events (AEs). In case of grade 3 or above toxicity, the dosage of oral-As2O3 will be reduced to 5mg per day. Changes or interruption in dosages, their dates and time points will be recorded on the dosage administration record and the electronic case report form (eCRF).
Interventions
Eligible subjects with NPM1 MRD positivity will receive oral arsenic trioxide (oral-As2O3) (Arsenol ®) (5-10mg per day, from days 1-7 per cycle), ascorbic acid (1g per day, from days 1 - 7 per cycle) plus azacitidine (75mg/m2 per day subcutaneously, from days 1 to 3 per cycle). Each cycle of oral-As2O3 plus azacitidine will be given once every 28 days. The total duration of treatment is 12 months (12 cycles). Treatment will be day-care and outpatient based. Reduction in the dosage and duration of oral-As2O3 is required if the subject is experiencing adverse events (AEs). In case of grade 3 or above toxicity, the dosage of oral-As2O3 will be reduced to 5mg per day.
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. Adults ≥ 18 years 2. Diagnosis of AML with NPM1 mutation 3. Positive MRD for NPM1 mutation after completion of consolidation in transplant-ineligible patients 4. Positive MRD for NPM1 mutation after allogeneic HSCT 5. bilirubin ≤ 1.5 x upper limit normal (ULN); alanine aminotransferase (ALT) ≤ 2 x ULN or aspartate aminotransferase (AST) ≤ 2 x ULN; and prothrombin time versus control \<3 seconds at screening 6. Glomerular filtration rate ≥ 50 mL/min (by MDRD equation or Cockcroft-Gault formula) 7. Corrected QT interval (QTc) (by Framingham formula) \<500ms. 8. Able to give a written informed consent and fully comply to the requirements of the study.
Exclusion criteria
1. Patients on other investigational therapies 2. Prior exposure to azacitidine, decitabine or arsenic trioxide 3. Uncontrolled graft-versus-host disease (GVHD) 4. Eastern Cooperative Oncology Group (ECOG) performance status \> 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of NPM1 MRD negativity. | 36 months | This is defined as undetectable NPM1 mutant transcript with RQ-PCR on both the PB and BM following treatment, at a limit of detection of 10\^-5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response | 36 months | defined as the time from achievement of undetectable NPM1 MRD to Documented molecular recurrence (defined as detectable MRD on PB or BM at a limit of detection of 10\^5. |
| Leukaemia-free survival (LFS) | 36 months | This is defined as the time, in months, from the start of oral-As2O3 plus azacitidine to morphologic relapse of AML. |
| Safety of oral-As2O3 plus azacitidine, assessed using the common toxicity criteria for adverse events (CTCAE) version 5.0. | 36 months | The incidence of treatment emergent adverse events will be determined as a measure of safety |
Countries
Hong Kong
Contacts
Primary ContactHarinder Gill, MD
Outcome results
None listed