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

Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia

Sponsors

Lead sponsor: The University of Hong Kong

Source 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

Overall Status Recruiting
Start Date August 15, 2018
Completion Date December 31, 2023
Primary Completion Date September 1, 2023
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Overall survival: Time (in months) from diagnosis to death or latest follow-up 60 months
Leukemia-free survival: Time (in months) from first remission to relapse, death or latest follow-up 60 months
Secondary Outcome
Measure Time Frame
Treatment Toxicity Grade 60 months
Enrollment 60
Condition
Intervention

Intervention type: Drug

Intervention name: Oral Arsenic Trioxide

Description: Oral arsenic trioxide-based frontline induction, consolidation and maintenance will be provided to patients with newly diagnosed acute promyelocytic leukemia.

Arm group label: Oral arsenic trioxide

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

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Harinder Singh Harry Gill, MBBS Principal Investigator Department of Medicine, the University of Hong Kong
Overall Contact

Last name: Harinder Singh Harry Gill, MBBS

Phone: +852 22554542

Email: [email protected]

Location
facility status contact Department of Medicine, the University of Hong Kong, Queen Mary Hospital Harinder Singh Harry Gill +852 22554542 [email protected]
Location Countries

Hong Kong

Verification Date

October 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Oral arsenic trioxide

Arm group type: Experimental

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) Consolidation: - Daunorubicin 50mg/m2 per day for 2 days + cytarabine 100mg/m2 per day for 5 days every 4 to 6 weeks for 2 cycles Consolidation (if WBC at diagnosis < 10 x 10^9/L; or aged ≥ 65 years; or cardiac function impairment): - 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.

Patient Data No
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov