Brief Title
Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia
Official Title
Risk-stratified Frontline Oral Arsenic Trioxide-based Induction in Newly Diagnosed Acute Promyelocytic Leukaemia
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
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Overall survival: Time (in months) from diagnosis to death or latest follow-up
Secondary Outcome
Treatment Toxicity Grade
Condition
Acute Promyelocytic Leukemia
Intervention
Oral arsenic Trioxide, ATRA and ascorbic acid
Study Arms / Comparison Groups
Frontline oral arsenic trioxide, ATRA and ascorbic acid (AAA)
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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
60
Start Date
August 15, 2018
Completion Date
December 31, 2023
Primary Completion Date
September 1, 2023
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Harinder Singh Harry Gill, MBBS, +852 22554542, [email protected]
Location Countries
Hong Kong
Location Countries
Hong Kong
Administrative Informations
NCT ID
NCT03624270
Organization ID
APL001
Responsible Party
Sponsor
Study Sponsor
The University of Hong Kong
Study Sponsor
Harinder Singh Harry Gill, MBBS, Principal Investigator, Department of Medicine, the University of Hong Kong
Verification Date
October 2022