Research Projects
Frontline Oral Arsenic Trioxide-Based Induction in Newly Diagnosed Acute Promyelocytic Leukaemia in Adults – A Multicentre Phase 2 Study


Programme(s) to which this project applies:
☒ MPhil/PhD ☑ MRes[Med] ☒ URIS

Objective and Significance:

Acute promyelocytic leukemia (APL) is characterized by t(15;17)(q24;21) and the fusion gene PML-RARA. Optimal supportive care with the use of all-trans retinoic acid (ATRA) and chemotherapy has resulted in first complete remission (CR1) rates of more than 90%, and long-term survivals of around 80%. Nevertheless, relapse occurs in up 20% 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, 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. For regimens comprising As2O3, ATRA and chemotherapy, 5-year OS in excess of 90% is achieved. We have also published long-term data showing the use of oral-As2O3 is highly effective and safe in the relapsed and frontline settings.

In this study, we evaluate the use of oral-As2O3 and ATRA based induction regimens in newly diagnosed patients with APL with no of minimal chemotherapy.

Objectives

To evaluate the efficacy and safety of frontline oral arsenic trioxide-based regimen in newly diagnosed APL with no or minimal chemotherapy.

Significance

This study will establish a completely chemotherapy-free approach for acute promyeloyctic leukaemia.

Research Plan and Methodology:

This is a prospective phase 2 study. After initial eligibility screening, patients will be recruited to oral arsenic trioxide, all-trans-retinoic acid, ascorbic acid (AAA) based-induction for 42 days. Daunorubicin (50mg/m2/day for 3 days) will only be used during induction in patients <65 with presenting white blood cell count (WBC) ≥ 10 x 109/L. In patients not receiving daunorubicin, hydroxyurea (2-4g/day) if WBC ≥ 5 x 109/L within the first 14 days of induction. Molecular monitoring monitoring with RQ-PCR or ddPCR for PML-RARA will be performed weekly during induction. A reassessment bone marrow aspirate will be performed on day 28 of induction for assessment of morphologic remission.

Four weeks after the completion of induction phase, all patients, regardless of initial WBC, will receive two cycles of chemotherapy-free AAA consolidation (14 days every 28 days).

Four weeks after completion of consolidation, all patients will receive 12 cycles of chemotherapy-free AAA maintenance (14 days every 8 week). Molecular monitoring monitoring with RQ-PCR or ddPCR for PML-RARA will be performed during every 4 weeks during consolidation, every 8 weeks during maintenance, and every 3 months for 24 months after completion of maintenance.

Primary outcomes

  1. Relapse-free survival (RFS), defined as the time (in months) from first complete morphologic remission (CR1) to morphologic or molecular relapse (event), or latest follow-up (censored).
  2. Event-free survival (EFS), defined as the time (in months) from recruitment to treatment failure (event), morphologic or molecular relapse (event), or latest follow-up (censored).

Secondary outcomes

  1. OS, defined as time (in months) from diagnosis to death (event) or latest follow-up (censored).
  2. Treatment toxicities by Common Toxicity Criteria for Adverse Everts (CTCAE) version 5.0.

Dr GHH Singh, Department of Medicine

Biography
gillhsh@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

  1. your CV,
  2. a brief description of your research interest and experience, and
  3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information. 

Research @ Department of Medicine