Oral Arsenic Trioxide for NPM1-mutated AML

Phase 2

Recruiting

• Conditions: NPMc+ AML
• Interventions: Drug: Oral Arsenic Trioxide Formulation

• Registration Number: NCT04689815
• Lead Sponsor: The University of Hong Kong

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).

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2020-12-24
• Study First Submitted QC: 2020-12-24
• Study First Posted: 2020-12-30
• Study Start: 2021-01-01
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-03
• Last Update Posted: 2022-10-04
• Primary Completion: 2023-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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.

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Oral arsenic trioxide-Azacitidine	Oral Arsenic Trioxide Formulation	12 monthly cycles of 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).

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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
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.

Trial Locations

Locations (1)

The University of Hong Kong; 🇭🇰 Hong Kong, Hong Kong