Oral Arsenic Trioxide for NPM1-mutated AML

October 3, 2022 updated by: The University of Hong Kong

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • The University of Hong Kong

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral arsenic trioxide-Azacitidine
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).
Drug: Oral Arsenic Trioxide Formulation
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.
Other Names:
  • Arsenol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of NPM1 MRD negativity.
Time Frame: 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.
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of response
Time Frame: 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.
36 months
Leukaemia-free survival (LFS)
Time Frame: 36 months
This is defined as the time, in months, from the start of oral-As2O3 plus azacitidine to morphologic relapse of AML.
36 months
Safety of oral-As2O3 plus azacitidine, assessed using the common toxicity criteria for adverse events (CTCAE) version 5.0.
Time Frame: 36 months
The incidence of treatment emergent adverse events will be determined as a measure of safety
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Investigators

  • Principal Investigator: Harinder Gill, The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2021

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

December 31, 2024

Study Registration Dates

First Submitted

December 24, 2020

First Submitted That Met QC Criteria

December 24, 2020

First Posted (Actual)

December 30, 2020

Study Record Updates

Last Update Posted (Actual)

October 4, 2022

Last Update Submitted That Met QC Criteria

October 3, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NPM1001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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