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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The University of Hong Kong

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 24, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 24, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 30, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 4, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 3, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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