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

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ClinicalTrials.gov Identifier: NCT04251754
Recruitment Status : Recruiting
First Posted : February 5, 2020
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
The University of Hong Kong

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.

Condition or disease
Acute Promyelocytic Leukemia

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.

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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: The Acute Promyelocytic Leukaemia Asian Consortium (APL-AC) Project
Actual Study Start Date : February 2, 2020
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : June 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia




Primary Outcome Measures :
  1. Survivals [ Time Frame: 60 months ]
    The primary outcome measures in this study include the overall survival (OS) and the relapse-free survival (RFS). OS is defined as the time (in months) from diagnosis to death from any cause (event) or latest follow-up. RFS is defined as the time from first complete remission (CR)/complete remission with incomplete haematological recovery (CRi) to first hamatologic relapse or molecular relapse (R1) (event), death from any cause (event) or latest follow-up (censor). CR, CRi, treatment failure, haematologic relapse are defined according to the 2017 European LeukemiaNet (ELN) recommendations. A molecular relapse is defined as recurrence of measurable residual disease (MRD) by reverse-transcriptase polymerase chain reaction (RT-PCR) or real-time quantitative PCR (qRT PCR). A single MRD positivity must be confirmed by performing the molecular assay within 2 weeks.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
This is a retrospective-prospective cohort study for all patients diagnosed with acute promyelocytic leukaemia since 2010 in Hong Kong and participating countries in Asia.
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04251754


Contacts
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Contact: Harinder Singh Harry Gill, MD +852 22554542 gillhsh@hku.hk

Locations
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Hong Kong
Department of Medicine, the University of Hong Kong, Queen Mary Hospital Recruiting
Hong Kong, Hong Kong
Contact: Harinder Singh Harry Gill, MD    +852 22554254    gillhsh@hku.hk   
Sponsors and Collaborators
The University of Hong Kong
Investigators
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Principal Investigator: Harinder Gill, MD The University of Hong Kong
Publications of Results:
Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. doi: 10.1056/NEJMoa1300874.
Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F. Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial. J Clin Oncol. 2017 Feb 20;35(6):605-612. doi: 10.1200/JCO.2016.67.1982. Epub 2016 Oct 31.

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Responsible Party: The University of Hong Kong
ClinicalTrials.gov Identifier: NCT04251754    
Other Study ID Numbers: APLAC001
First Posted: February 5, 2020    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid