Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia

Phase 2

Recruiting

• Conditions: Acute Promyelocytic Leukemia
• Interventions: Drug: Oral arsenic Trioxide, ATRA and ascorbic acid

• Registration Number: NCT03624270
• Lead Sponsor: The University of Hong Kong

Brief Summary

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

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-08-05
• Study First Submitted QC: 2018-08-07
• Study First Posted: 2018-08-10
• Study Start: 2018-08-15
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-03
• Last Update Posted: 2022-10-04
• Primary Completion: 2023-09-01
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Frontline oral arsenic trioxide, ATRA and ascorbic acid (AAA)	Oral arsenic Trioxide, ATRA and ascorbic acid	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Treatment Toxicity Grade	60 months	Treatment toxicities by Eastern Cooperative Oncology (ECOG)-Common Toxicity Criteria (CTC)

Trial Locations

Locations (1)

Department of Medicine, the University of Hong Kong, Queen Mary Hospital; 🇭🇰 Hong Kong, N/A = Not Applicable, Hong Kong