search
Back to results

Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia

Primary Purpose

Acute Promyelocytic Leukemia

Status
Recruiting
Phase
Phase 2
Locations
Hong Kong
Study Type
Interventional
Intervention
Oral arsenic Trioxide, ATRA and ascorbic acid
Sponsored by
The University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Promyelocytic Leukemia focused on measuring Acute promyelocytic leukaemia, Oral arsenic trioxide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Department of Medicine, the University of Hong Kong, Queen Mary HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm 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.

Outcomes

Primary Outcome Measures

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)
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)

Secondary Outcome Measures

Treatment Toxicity Grade
Treatment toxicities by Eastern Cooperative Oncology (ECOG)-Common Toxicity Criteria (CTC)

Full Information

First Posted
August 5, 2018
Last Updated
October 3, 2022
Sponsor
The University of Hong Kong
search

1. Study Identification

Unique Protocol Identification Number
NCT03624270
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 15, 2018 (Actual)
Primary Completion Date
September 1, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Hong Kong

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Promyelocytic Leukemia
Keywords
Acute promyelocytic leukaemia, Oral arsenic trioxide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Frontline oral arsenic trioxide, ATRA and ascorbic acid (AAA)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Oral arsenic Trioxide, ATRA and ascorbic acid
Intervention Description
Oral arsenic trioxide-based frontline induction, consolidation and maintenance will be provided to patients with newly diagnosed acute promyelocytic leukemia.
Primary Outcome Measure Information:
Title
Overall survival: Time (in months) from diagnosis to death or latest follow-up
Description
Time (in months) from diagnosis to death (event) or latest follow-up (censor)
Time Frame
60 months
Title
Leukemia-free survival: Time (in months) from first remission to relapse, death or latest follow-up
Description
Time (in months) from first remission to relapse (event), death (event) or latest follow-up (censor)
Time Frame
60 months
Secondary Outcome Measure Information:
Title
Treatment Toxicity Grade
Description
Treatment toxicities by Eastern Cooperative Oncology (ECOG)-Common Toxicity Criteria (CTC)
Time Frame
60 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Harinder Singh Harry Gill, MBBS
Phone
+852 22554542
Email
gillhsh@hku.hk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harinder Singh Harry Gill, MBBS
Organizational Affiliation
Department of Medicine, the University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Medicine, the University of Hong Kong, Queen Mary Hospital
City
Hong Kong
State/Province
N/A = Not Applicable
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Harinder Singh Harry Gill
Phone
+852 22554542
Email
gillhsh@hku.hk

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan for IPD to be shared.

Learn more about this trial

Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia

We'll reach out to this number within 24 hrs