Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia

Study Overview
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Brief Summary
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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

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

Conditions
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Acute Promyelocytic Leukemia

Intervention / Treatment
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* Drug: Oral arsenic Trioxide, ATRA and ascorbic acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Frontline oral arsenic trioxide, ATRA and ascorbic acid (AAA)<br>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<br>* Oral arsenic trioxide-based frontline induction, consolidation and maintenance will be provided to patients with newly diagnosed acute promyelocytic leukemia.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute promyelocytic leukaemia, Oral arsenic trioxide