oral arsenic with atra for newly diagnosed patients with acute promyelocytic leukemia

Conditions: Acute Promyelocytic Leukemia (APL)

Summary: it is a non-randomized, multicenter, prospective study, aiming to treat patients with newly diagnosed acute promyelocytic leukemia with a combination of oral arsenic and atra, with low dose chemotherapy for those with high-risk disease (white blood cell count above 10x10a9/l). the primary objective is to assess the 2-year overall survival (os) in these patients, comparing with the historical control group of patients treated with atra/chemotherapy according to the ic-apl 2006 protocol.

this is a non-randomized, multicenter, prospective study aimed at treating patients with newly diagnosed acute promyelocytic leukemia (apl) using a combination of oral arsenic and atra. for patients classified as high-risk (white blood cell count \>10×10⁹/l), low-dose chemotherapy will be added. the primary objective is to evaluate the 2-year overall survival (os) in these patients, comparing it to a historical control group treated with atra and chemotherapy according to the ic-apl 2006 protocol. secondary objectives include: comparing complete response rates, disease-free survival, cumulative incidence of relapse, and early mortality with those reported in the ic-apl 2006 study (historical controls), as well as with outcomes reported in developed countries; comparing the cumulative incidence of myelodysplasia or secondary leukemia; comparing the toxicity profile with historical data; assessing the molecular remission rate after consolidation; evaluating the reduction in pml/rara transcript levels during treatment; comparing the duration of patient hospitalization with historical results.

Eligibility criteria:
inclusion criteria: * informed consent * new diagnosis of apl by cytomorphology, confirmed for molecular analysis * age ≥18 and ≤75 years * serum total bilirubin ≤ 3.0 mg/dl (≤ 51 μmol/l) * serum creatinine ≤ 3.0 mg/dl (≤ 260 μmol/l) * women must meet at least one of the following criteria to be eligible for inclusion in the study: postmenopausal (12 months of amenorrhea or 6 months of amenorrhea with serum fsh \> 40 u/ml); after undergoing hysterectomy or bilateral oophorectomy; continuous and correct use of a contraceptive method with a pearl index \<1% (e.g., implants, oral contraceptives, intrauterine devices); sexual abstinence; vasectomy of sexual partner. exclusion criteria: * high-risk patients who are not eligible for chemotherapy according to the judgment of the treating physician; * age \ 75 years * other active malignancy at the time of study entry * lack of diagnostic confirmation at the genetic level * significant arrhythmias, ecg abnormalities, or neuropathy: congenital long qt syndrome; history or presence of significant ventricular or atrial tachyarrhythmia; clinically significant resting bradycardia (\ 500 ms on ecg screening for both sexes; right bundle branch block with left anterior hemiblock or bifascicular block * high-risk patients with other cardiac contraindications for intensive chemotherapy (lvef \< 50%) * uncontrolled and potentially fatal infections * severe uncontrolled pulmonary or cardiac disease * severe hepatic or renal dysfunction * known hiv and/or hepatitis c infection * pregnant or breastfeeding women * allergy to the study drug or excipients in the study medication * substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or the assessment of study outcomes * use of other investigational drugs at the time of enrollment or within 30 days before study entry.

Keywords: acute promyelocytic leukemia oral arsenic survival all trans-retinoic acid