NPMc+ AML Clinical Trial
Official title:
Measurable-residual Disease (MRD) Monitoring of Nucleophosmin 1 (NPM1)-Mutated Acute Myeloid Leukaemia (AML) and Pre-emptive Therapy With Oral Arsenic Trioxide-based Regimen
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.
| Status | Recruiting |
| Enrollment | 50 |
| Est. completion date | December 31, 2024 |
| Est. primary completion date | December 31, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Hong Kong | The University of Hong Kong | Hong Kong |
| Lead Sponsor | Collaborator |
|---|---|
| The University of Hong Kong |
Hong Kong,
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| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Rate of NPM1 MRD negativity. | 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. | 36 months | |
| Secondary | Duration of response | 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. | 36 months | |
| Secondary | Leukaemia-free survival (LFS) | This is defined as the time, in months, from the start of oral-As2O3 plus azacitidine to morphologic relapse of AML. | 36 months | |
| Secondary | Safety of oral-As2O3 plus azacitidine, assessed using the common toxicity criteria for adverse events (CTCAE) version 5.0. | The incidence of treatment emergent adverse events will be determined as a measure of safety | 36 months |