Frontline Oral Arsenic Trioxide for APL
ConditionAcute Promyelocytic Leukemia
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorThe University of Hong Kong
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Ability and willingness to comply with the study procedures and restrictions
Voluntary written informed consent
Disqualifiers
ECOG performance score >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)
Trial design
Design model
Single group
Treatments tested in this trial
Oral Arsenic Trioxide Formulation
DrugPatients 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).
Treatment groups
100 Participants
are divided into 1 treatment groupGroup A: Oral arsenic trioxide, all-trans-retinoic acid, ascorbic acid (AAA)Experimental treatment 1 intervention
Trial outcomes
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).
Time frame
60 months2
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).
Time frame
60 monthsSecondary outcomes
1
Overall survival
Defined as time (in months) from diagnosis to death (event) or latest follow-up (censored).
Time frame
60 months2
Treatment toxicities
Treatment toxicities by Common Toxicity Criteria for Adverse Everts (CTCAE) version 5.0.
Time frame
60 monthsSponsors and contacts
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Source ClinicalTrials.gov