The Acute Promyelocytic Leukaemia Asian Consortium (APL-AC) Project

NCT ID: NCT04251754

Last Updated: 2022-10-04

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-02-02
• Study Completion Date: 2025-06-30

Brief Summary

There is currently lack of collaborative data on the epidemiology, clinicopathologic features and treatment outcome of newly diagnosed and relapsed APL in Asia. In addition, there is lack of data comparing oral- As2O3-based regimens with other treatment approaches, including intravenous As2O3,in the frontline or relapsed setting. With the long-term data of oral-As2O3 based regimen for APL available from Hong Kong, retrospective and prospective comparison with other treatment approaches in other Asian countries will generate important information to pave the way for widespread application of oral-As2O3 outside Hong Kong.

Detailed Description

Acute promyelocytic leukemia (APL) is characterized by t(15;17)(q24;21) and the fusion gene PML-RARA.1 In newly-diagnosed patients, optimal supportive care together with the use of all-trans retinoic acid (ATRA) and chemotherapy results in first complete remission (CR1) in excess of 90% with durable remissions in about 80% of patients.Arsenic trioxide (As2O3) given intravenously (i.v.-As2O3) is highly efficacious for APL in first relapse (R1), inducing second complete remission (CR2) in more than 90% of patients. We have formulated an oral preparation of As2O3 (oral-As2O3), and shown that it is efficacious for APL in R1, giving CR2 rates of more than 90% in both adults and children. For patients in CR2, a 2-year maintenance with oral-As2O3 results in durable remission and long-term survivals in more than 60% and 70% of patients respectively strongly suggesting that hematopoietic stem cell transplantation (HSCT) could be obviated in such patients. With these results, we implemented oral-As2O3 maintenance in CR1 in Hong Kong and demonstrated very favourable overall-survival (OS) and leukemia-free-survival (LFS). This implied that that prolonged oral-As2O3 treatment may prevent relapses.

Meanwhile, i.v.-As2O3 has also been tested in the frontline treatment of newly-diagnosed APL.These studies employed different strategies, recruiting a mixture of low-, intermediate- to high-risk patients and placing i.v.-As2O3 in induction and/or consolidation. During induction, i.v.-As2O3 was combined with ATRA, with additional gemtuzumab ozogamicin (an anti-CD33 immunoconjugate) or chemotherapy. During consolidation, i.v.-As2O3 was combined with conventional chemotherapy. Their results all indicated that frontline use of i.v.-As2O3 in induction and/or consolidation improved the outcome of newly-diagnosed APL patients. However, with quite diverse protocols and the enrollment in some studies of only patients with low to intermediate risks, and in other studies of patients with all risk categories; the optimal strategy of employing i.v.-As2O3 in newly-diagnosed APL remains to be defined. We have tested oral- As2O3 in combination with ATRA, ascorbic acid (AAA) with daunorubicin in both low-risk and high-risk APL with 3 year LFS and OS of both 100%.

With the impressive results of oral-As2O3-based regimen in newly diagnosed and relapsed APL, an important future perspective is the application of this relatively economical and convenient approach to the treatment of patients with APL in Asia and other developing countries around the world where the cost and availability of intravenous formulation of As2O3 is a concern. There is currently lack of collaborative data on the epidemiology, clinicopathologic features and treatment outcome of newly diagnosed and relapsed APL in Asia. In addition, there is lack of data comparing oral- As2O3-based regimens with other treatment approaches, including intravenous As2O3,in the frontline or relapsed setting. With the long-term data of oral-As2O3 based regimen for APL available from Hong Kong, retrospective and prospective comparison with other treatment approaches in other Asian countries will generate important information to pave the way for widespread application of oral-As2O3 outside Hong Kong.

Conditions

Acute Promyelocytic Leukemia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients aged 18 or above
• Acute promyelocytic leukaemia with PML/RARA
• Acute myeloid leukaemia with variant RARA translocation

Exclusion Criteria

-Acute myeloid leukaemia without PML/RARA or variant RARA translocation

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Harinder Gill, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

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

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Harinder Singh Harry Gill, MD

Role: CONTACT

gillhsh@hku.hk

+852 22554542

Facility Contacts

Harinder Singh Harry Gill, MD

Role: primary

gillhsh@hku.hk

+852 22554254

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Other Identifiers

APLAC001

Identifier Type: -

Identifier Source: org_study_id