Clinical trial
Frontline Oral Arsenic Trioxide-based Induction in Newly Diagnosed Acute Promyelocytic Leukaemia
Name
APL003
Description
The investigators have formulated an oral preparation of arsenic trioxide (oral-ATO), and shown that it is efficacious for APL in R1, inducing CR2 in more than 90% of patients \[8,9\]. Furthermore, in an effort to prevent relapse, the investigators have moved oral-ATO forward to the maintenance of CR1. This strategy results in favorable overall-survival (OS) and leukemia-free-survival (LFS) \[10\], implying that prolonged treatment with oral-ATO may prevent relapses.
Current protocols have incorporated i.v.-ATO in the treatment of newly-diagnosed APL \[11-15\]. For regimens comprising oral-ATO, ATRA and chemotherapy, 5-year OS in excess of 90% is achieved \[11-15\].
The investigators have also published long-term data showing the use of oral-ATO is highly effective and safe in the relapsed and frontline settings \[16,17\].
In this study, the investigators evaluate the use of oral-ATO and ATRA based induction regimens in newly diagnosed patients with APL with no of minimal chemotherapy in a prospective multicentre phase 2 study.
Trial arms
Trial start
2021-01-01
Estimated PCD
2025-12-31
Trial end
2026-06-30
Status
Recruiting
Phase
Early phase I
Treatment
Oral Arsenic Trioxide Formulation
Patients will be recruited to oral arsenic trioxide, all-trans-retinoic acid, ascorbic acid (AAA) based-induction for 42 days. Daunorubicin or idarubicin will only be used during induction in patients \<65 with presenting white blood cell count (WBC) ≥ 10 x 10\^9/L. In patients not receiving daunorubicin, hydroxyurea if WBC ≥ 5 x 10\^9/L within the first 14 days of 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).
Arms:
Oral arsenic trioxide, all-trans-retinoic acid, ascorbic acid (AAA)
Other names:
ARSENOL
Size
100
Primary endpoint
Relapse-free survival (RFS)
60 months
Event-free survival (EFS)
60 months
Eligibility criteria
Inclusion Criteria:
1. Newly diagnosed APL with t(15;17)(q24;q21) or acute myeloid leukaemia (AML) with variant RARA translocation according to the World Health Organization (WHO) Classification 2022
2. Ability and willingness to comply with the study procedures and restrictions
3. Voluntary written informed consent
Exclusion Criteria:
1. ECOG performance score \>2
2. Decompensated heart failure with left-ventricular ejection fraction of less than 40% and global hypokinesia on echocardiogram.
3. Prolonged corrected QT interval (QTc) ≥ 500ms, in the absence of electrolyte disturbances and medications known to prolong QTc
4. Significant liver function derangement (Bilirubin \> 3 times upper limit normal and/or ALT \> 5 times upper limit of normal)
5. Glomerular filtration rate (GRF) by Cockcroft-Gault formula or eGFR (MDRD) of less than 30mL/min in adults (aged ≥ 18) or Creatinine clearance \< 50ml/min/1.73m2 in paediatric and adolescent patients (Age ≤ 17)
6. Female subject who is lactating or has positive pregnancy test result prior to the first dose of study drug
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 100, 'type': 'ESTIMATED'}}
Updated at
2023-05-23
1 organization
1 product
1 indication
Organization
The University of Hong KongProduct
Arsenic TrioxideIndication
Acute Promyelocytic Leukemia