Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia

NCT03624270 | Unknown Phase 2 DMC

• 1 other identifier: APL001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Conditions

Acute Promyelocytic Leukemia

Keywords

Acute promyelocytic leukaemia; Oral arsenic trioxide

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Treatment Toxicity Grade

  60 months

Study Arms (1)

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

EXPERIMENTAL

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

Interventions

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.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Department of Medicine, the University of Hong Kong, Queen Mary Hospital

Hong Kong, N/A = Not Applicable, Hong Kong

RECRUITING

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

Arsenic Trioxide; Tretinoin; Ascorbic Acid

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Harinder Singh Harry Gill, MBBS

  Department of Medicine, the University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Harinder Singh Harry Gill, MBBS

CONTACT

+852 22554542; gillhsh@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2018
• First Posted: August 10, 2018
• Study Start: August 15, 2018
• Primary Completion: September 1, 2023
• Study Completion: December 31, 2023
• Last Updated: October 4, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)