Frontline Oral Arsenic Trioxide for APL

May 21, 2023 updated by: The University of Hong Kong

Frontline Oral Arsenic Trioxide-based Induction in Newly Diagnosed Acute Promyelocytic Leukaemia

The investigators have formulated an oral preparation of arsenic trioxide (oral-ATO), and shown that it is efficacious for APL in R1, inducing CR2 in more than 90% of patients [8,9]. Furthermore, in an effort to prevent relapse, the investigators have moved oral-ATO forward to the maintenance of CR1. This strategy results in favorable overall-survival (OS) and leukemia-free-survival (LFS) [10], implying that prolonged treatment with oral-ATO may prevent relapses.

Current protocols have incorporated i.v.-ATO in the treatment of newly-diagnosed APL [11-15]. For regimens comprising oral-ATO, ATRA and chemotherapy, 5-year OS in excess of 90% is achieved [11-15].

The investigators have also published long-term data showing the use of oral-ATO is highly effective and safe in the relapsed and frontline settings [16,17].

In this study, the investigators evaluate the use of oral-ATO and ATRA based induction regimens in newly diagnosed patients with APL with no of minimal chemotherapy in a prospective multicentre phase 2 study.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

After initial eligibility screening, patients will be recruited to oral arsenic trioxide, all-trans-retinoic acid, ascorbic acid (AAA) based-induction for 42 days. Daunorubicin or idarubicin will only be used during induction in patients <65 with presenting white blood cell count (WBC) ≥ 10 x 10^9/L. In patients not receiving daunorubicin, hydroxyurea if WBC ≥ 5 x 10^9/L within the first 14 days of induction. Molecular monitoring monitoring with RQ-PCR or ddPCR for PML-RARA will be performed weekly during induction. A reassessment bone marrow aspirate will be performed on day 28 of induction for assessment of morphologic remission.

Four weeks after the completion of induction phase, all patients, regardless of initial WBC, will receive two cycles of chemotherapy-free AAA consolidation (14 days every 28 days).

Four weeks after completion of consolidation, all patients will receive 12 cycles of chemotherapy-free AAA maintenance (14 days every 8 week).

Molecular monitoring monitoring with RQ-PCR or ddPCR for PML-RARA will be performed during every 4 weeks during consolidation, every 8 weeks during maintenance, and every 3 months for 24 months after completion of maintenance.

Study Type

Interventional

Enrollment (Anticipated)

100

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 Contact

  • Name: Harry Gill, MD
  • Phone Number: +852 22554542
  • Email: gillhsh@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • The University of Hong Kong
        • Contact:
        • Sub-Investigator:
          • Yok-lam Kwong, MD

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 (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Newly diagnosed APL with t(15;17)(q24;q21) or acute myeloid leukaemia (AML) with variant RARA translocation according to the World Health Organization (WHO) Classification 2022
  2. Ability and willingness to comply with the study procedures and restrictions
  3. Voluntary written informed consent

Exclusion Criteria:

  1. ECOG performance score >2
  2. Decompensated heart failure with left-ventricular ejection fraction of less than 40% and global hypokinesia on echocardiogram.
  3. Prolonged corrected QT interval (QTc) ≥ 500ms, in the absence of electrolyte disturbances and medications known to prolong QTc
  4. Significant liver function derangement (Bilirubin > 3 times upper limit normal and/or ALT > 5 times upper limit of normal)
  5. Glomerular filtration rate (GRF) by Cockcroft-Gault formula or eGFR (MDRD) of less than 30mL/min in adults (aged ≥ 18) or Creatinine clearance < 50ml/min/1.73m2 in paediatric and adolescent patients (Age ≤ 17)
  6. Female subject who is lactating or has positive pregnancy test result prior to the first dose of study drug

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, all-trans-retinoic acid, ascorbic acid (AAA)

Induction: Oral arsenic trioxide 10mg daily (0.16mg/kg/day in patients < 18 years-old, all-trans retinoic acid (ATRA) [45mg/m^2 (25mg/m^2 per day in patients < 18 years-old) in 2 divided doses) and ascorbic acid 1g daily (15mg/kg/day in patients < 18 years-old) for 42 days Consolidation: Oral arsenic trioxide daily, ATRA, and ascorbic acid daily for 14 days every 28 days for 2 cycles.

Maintenance: Oral arsenic trioxide, ATRA and ascorbic acid daily for 2 weeks every 8 weeks for a total of 2 years (i.e. for 12 cycles in total).
Drug: Oral Arsenic Trioxide Formulation

Patients will be recruited to oral arsenic trioxide, all-trans-retinoic acid, ascorbic acid (AAA) based-induction for 42 days. Daunorubicin or idarubicin will only be used during induction in patients <65 with presenting white blood cell count (WBC) ≥ 10 x 10^9/L. In patients not receiving daunorubicin, hydroxyurea if WBC ≥ 5 x 10^9/L within the first 14 days of induction. A reassessment bone marrow aspirate will be performed on day 28 of induction for assessment of morphologic remission.

Four weeks after the completion of induction phase, all patients, regardless of initial WBC, will receive two cycles of chemotherapy-free AAA consolidation (14 days every 28 days).

Four weeks after completion of consolidation, all patients will receive 12 cycles of chemotherapy-free AAA maintenance (14 days every 8 week).

Other Names:
  • ARSENOL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse-free survival (RFS)
Time Frame: 60 months
Defined as the time (in months) from first complete morphologic remission (CR1) to morphologic or molecular relapse (event), or latest follow-up (censored).
60 months
Event-free survival (EFS)
Time Frame: 60 months
Defined as the time (in months) from recruitment to treatment failure (event), morphologic or molecular relapse (event), or latest follow-up (censored).
60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 60 months
Defined as time (in months) from diagnosis to death (event) or latest follow-up (censored).
60 months
Treatment toxicities
Time Frame: 60 months
Treatment toxicities by Common Toxicity Criteria for Adverse Everts (CTCAE) version 5.0.
60 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: Harry Gill, MD, 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, 2025

Study Completion (Anticipated)

June 30, 2026

Study Registration Dates

First Submitted

December 23, 2020

First Submitted That Met QC Criteria

December 23, 2020

First Posted (Actual)

December 29, 2020

Study Record Updates

Last Update Posted (Actual)

May 23, 2023

Last Update Submitted That Met QC Criteria

May 21, 2023

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APL003

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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