Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia

The University of Hong Kong (HKU)

Status and phase: Enrolling; Phase 2

Conditions: Acute Promyelocytic Leukemia

Treatments: Drug: Oral arsenic Trioxide, ATRA and ascorbic acid

Study type: Interventional

Funder types: Other

Identifiers

NCT03624270

APL001

Details and patient eligibility

About

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

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Frontline oral arsenic trioxide, ATRA and ascorbic acid (AAA)

Experimental group

Description:

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.

Treatment:

Drug: Oral arsenic Trioxide, ATRA and ascorbic acid