Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia

NCT03624270 — Phase 2, Unknown, 60 participants, The University of Hong Kong

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

Registry	NCT03624270
Status	Unknown
Phase	Phase 2
Study type	Interventional; na, single group, masking: none, treatment
Enrollment	60 (Estimated)
Sponsor	The University of Hong Kong (Other)
Conditions	Acute Promyelocytic Leukemia
Interventions	Oral arsenic Trioxide, ATRA and ascorbic acid (Drug)
Dates	start 2018-08-15, primary completion 2023-09-01 (estimated), completion 2023-12-31 (estimated), first posted 2018-08-10, last updated 2022-10-04
Locations	1 site in Hong Kong

-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

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+Arms and interventions

Arm	Type	Interventions	Description
Frontline oral arsenic trioxide, ATRA and ascorbic acid (AAA)	Experimental	Drug: 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.

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

+Outcome measures

Primary outcomes

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)
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)

Secondary outcomes

Treatment Toxicity Grade [60 months]: Treatment toxicities by Eastern Cooperative Oncology (ECOG)-Common Toxicity Criteria (CTC)

+Eligibility

Sex: All, ages: 18 Years to any

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

+Locations (1)

Facility	City	Country	Status
Department of Medicine, the University of Hong Kong, Queen Mary Hospital	Hong Kong, N/A = Not Applicable	Hong Kong	Recruiting

+Investigators

Harinder Singh Harry Gill, MBBS, Principal investigator, Department of Medicine, the University of Hong Kong