Combination of Oral Arsenic With ATRA and Minimal-Dose Chemotherapy for Newly Diagnosed Patients With Acute Promyelocytic Leukemia: a Study by the International Consortium on APL

Phase 2

Recruiting

• Conditions: Acute Promyelocytic Leukemia (APL)
• Interventions: Drug: Realgar-Indigo Naturalis Formulation

• Registration Number: NCT06982274
• Lead Sponsor: Instituto do Cancer do Estado de São Paulo

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

Not available

Study Timeline

• Study Start: 2023-10-20
• Status Verified: 2025-05
• Study First Submitted: 2025-05-13
• Study First Submitted QC: 2025-05-13
• Last Update Submitted: 2025-05-13
• Study First Posted: 2025-05-21
• Last Update Posted: 2025-05-21
• Primary Completion: 2028-11
• Study Completion: 2029-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 115

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Proposed protocol	Realgar-Indigo Naturalis Formulation	Oral Arsenic + ATRA with low-dose daunorubicin for high-risk patients

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.

Trial Locations

Locations (1)

Instituto do Cancer do Estado de Sao Paulo; 🇧🇷 Sao Paulo, SP, Brazil