Acute Promyelocytic Leukemia (APL)
Conditions
Keywords
Acute promyelocytic leukemia, Oral arsenic, Survival, All trans-retinoic acid
Brief 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.
Detailed 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.
Interventions
Oral Arsenic (Realgar-Indigo Naturalis Formulation) plus ATRA for low-intermediate risk APL pts, combined with daunorubicin for high-risk during induction
Sponsors
American Society of Hematology
Instituto do Cancer do Estado de São Paulo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 2 years | This endpoint includes death from any cause, including early death, death due to disease progression, or any death occurring after achieving complete remission. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early death rate during induction | 30 days | Death before blood cell counts recovery during induction. |
| Disease-free survival rate | 2 years | The proportion of patients who remain alive and in complete remission, without evidence of relapse, for at least two years following achievement of initial complete remission. |
| Cumulative incidence of myelodysplasia and secondary leukemia | 5 years | The proportion of patients who develop myelodysplastic syndromes or secondary leukemia after treatment. |
| Complete hematologic response rate after induction. | 30 days | Absence of leukemic promyelocytes in the peripheral blood and bone marrow (\<5% blasts), recovery of normal blood counts (ANC ≥ 1.0 × 10⁹/L and platelets ≥ 100 × 10⁹/L), no extramedullary disease, and resolution of coagulopathy. |
| Molecular remission rate after consolidation | 150 days | The proportion of patients who achieve a negative molecular test by PCR for PML-RARA after completing the consolidation phase of treatment. |
| PML/RARA transcript level during treatment | Each 3 months | The quantitative measurement of the PML/RARA fusion gene transcript, assessed by PCR, at various stages of therapy. |
| Days of hospitalization during treatment | 180 days | The total length of time a patient spends in the hospital for the administration of treatment, management of complications, or observation during the course of therapy. |
| Cumulative incidence of relapse | 2 years | The proportion of patients who experience a relapse of acute leukemia within two years of achieving complete remission, accounting for competing risk of death without relapse. |
Countries
Brazil
Contacts
Primary ContactElaine Uehara
Outcome results
None listed