Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia

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

Acute promyelocytic leukemia (APL) is characterized by t(15;17)(q24;21) and the fusion gene PML-RARA. We have formulated an oral preparation of As2O3 (oral-As2O3), and shown that it is efficacious for APL in R1, inducing CR2 in more than 90% of patients. Furthermore, in an effort to prevent relapse, we have moved oral-As2O3 forward to the maintenance of CR1. This strategy results in favorable overall-survival (OS) and leukemia-free-survival (LFS), implying that prolonged treatment with oral-As2O3 may prevent relapses. Current protocols have incorporated i.v.-As2O3 in the treatment of newly-diagnosed APL. In regimens comprising i.v.-As2O3, ATRA and chemotherapy, 5-year overall survivals in excess of 90% is achieved. In this study, we evaluate the use of oral-As2O3 and ATRA based induction regimens in newly diagnosed patients with APL. In this study, we evaluate the efficacy and tolerability of frontline oral arsenic trioxide-based regimen in newly diagnosed patients with acute promyelocytic leukaemia

Study Overview

• Status: Recruiting
• Conditions: Acute Promyelocytic Leukemia
• Intervention / Treatment: Drug: Oral arsenic Trioxide, ATRA and ascorbic acid

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Harinder Singh Harry Gill, MBBS; Phone Number: +852 22554542; Email: gillhsh@hku.hk

Study Locations

• Hong Kong
  • N/A = Not Applicable
    • Hong Kong, N/A = Not Applicable, Hong Kong
      • Recruiting
      • Department of Medicine, the University of Hong Kong, Queen Mary Hospital
      • Contact: Harinder Singh Harry Gill; Phone Number: +852 22554542; Email: gillhsh@hku.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly diagnosed patients with acute promyelocytic leukaemia (APL) with t(15;17) (q24;q21)according to the World Health Organization (WHO) Classification 2016
• Patients aged ≥18 years
• Able and willing to comply with the study procedures and restrictions
• Having given voluntary written informed consent

Exclusion Criteria:

• ECOG performance status above 2
• Decompensated heart failure with left-ventricular ejection fraction of less than 40% and global hypokinesia on echocardiogram.
• Prolonged corrected QT interval (QTc) > 500ms, in the absence of electrolyte disturbances and medications known to prolong QTc
• Significant liver function derangement (Bilirubin > 3 times upper limit normal and/or ALT > 5 times upper limit of normal)
• Acute myeloid leukaemia with variant RARA translocation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Frontline oral arsenic trioxide, ATRA and ascorbic acid (AAA); Induction: Oral arsenic trioxide 10mg daily, all-trans retinoic acid (ATRA) (45mg/m2 per day in divided doses) and Ascorbic acid 1g daily for 42 days; Daunorubicin at 50mg/m2 daily for 3 days (omitted if WBC at diagnosis < 10 x 10^9/L; or age ≥ 65 years; or cardiac function impairment); Hydroxyurea 2-4g per day if WBC > 5 x 10^9/L during the first 7 days of induction. Consolidation (for all patients): - Oral arsenic trioxide 10mg daily, all-trans retinoic acid (ATRA) (45mg/m2 per day in divided doses) and ascorbic acid 1g daily for 14 days every 28 days for 2 cycles Maintenance (for all patients): - Oral Arsenic trioxide 10mg daily, ATRA (45mg/m2 per day in divided doses) and ascorbic acid 1g daily for 2 weeks every 2 months for 24 months.

Drug: Oral arsenic Trioxide, ATRA and ascorbic acid; Oral arsenic trioxide-based frontline induction, consolidation and maintenance will be provided to patients with newly diagnosed acute promyelocytic leukemia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival: Time (in months) from diagnosis to death or latest follow-up	Time (in months) from diagnosis to death (event) or latest follow-up (censor)	60 months
Leukemia-free survival: Time (in months) from first remission to relapse, death or latest follow-up	Time (in months) from first remission to relapse (event), death (event) or latest follow-up (censor)	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Toxicity Grade	Treatment toxicities by Eastern Cooperative Oncology (ECOG)-Common Toxicity Criteria (CTC)	60 months

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Harinder Singh Harry Gill, MBBS, Department of Medicine, the University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2018
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: August 5, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (Actual): August 10, 2018

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: Acute promyelocytic leukaemia; Oral arsenic trioxide
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia; Leukemia, Promyelocytic, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Micronutrients; Vitamins; Antioxidants; Arsenic Trioxide; Ascorbic Acid
• Other Study ID Numbers: APL001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan for IPD to be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No