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Oral Arsenic Trioxide for NPM1-mutated AML

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04689815
Recruitment Status : Recruiting
First Posted : December 30, 2020
Last Update Posted : December 31, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
NPMc+ AML Drug: Oral Arsenic Trioxide Formulation Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : January 1, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2024


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 Name: Arsenol




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04689815


Contacts
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Contact: Harinder Gill, MD +852 22554542 gillhsh@hku.hk

Locations
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Hong Kong
The University of Hong Kong Recruiting
Hong Kong, Hong Kong
Contact: Harinder Gill, MD    85222554542    gillhsh@hku.hk   
Sub-Investigator: Yok-Lam Kwong, MD         
Sponsors and Collaborators
The University of Hong Kong
Investigators
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Principal Investigator: Harinder Gill The University of Hong Kong
Publications:

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Responsible Party: The University of Hong Kong
ClinicalTrials.gov Identifier: NCT04689815    
Other Study ID Numbers: NPM1001
First Posted: December 30, 2020    Key Record Dates
Last Update Posted: December 31, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The University of Hong Kong:
NPM1 mutation
Acute myeloid leukemia
Oral arsenic trioxide
Additional relevant MeSH terms:
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Arsenic Trioxide
Antineoplastic Agents