Overview
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.
Description
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
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 <18 or >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 (<50 beats per minute); QTc > 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.