Oral Arsenic With ATRA for Newly Diagnosed Patients With Acute Promyelocytic Leukemia

NCT ID: NCT06982274

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-20
• Study Completion Date: 2029-11-30

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.

Conditions

Acute Promyelocytic Leukemia (APL)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Proposed protocol

Oral Arsenic + ATRA with low-dose daunorubicin for high-risk patients

Group Type: EXPERIMENTAL

Realgar-Indigo Naturalis Formulation

Intervention Type: DRUG

Oral Arsenic (Realgar-Indigo Naturalis Formulation) plus ATRA for low-intermediate risk APL pts, combined with daunorubicin for high-risk during induction

Interventions

Realgar-Indigo Naturalis Formulation

Oral Arsenic (Realgar-Indigo Naturalis Formulation) plus ATRA for low-intermediate risk APL pts, combined with daunorubicin for high-risk during induction

Intervention Type: DRUG

Other Intervention Names

Oral Arsenic

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 <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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Society of Hematology

OTHER

Sponsor Role: collaborator

Instituto do Cancer do Estado de São Paulo

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eduardo M Rego, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto do Cancer do Estado de Sao Paulo

Locations

Instituto do Cancer do Estado de Sao Paulo

São Paulo, São Paulo, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Elaine Uehara

Role: CONTACT

elaine.uuehara@hc.fm.usp.br

55 38933535

Facility Contacts

Wellington Silva, MD PhD

Role: primary

wellington.fernandes@hc.fm.usp.br

55 11 38934144

Rodrigo Bonardi, MD

Role: backup

rodrigo.bonardi@hc.fm.usp.br

55 11 38934144

References

Silva WF, Kim HT, Undurraga MS, Navarro-Cabrera JR, Salinas V, Muxi P, Melo RAM, Gloria ABF, Pagnano KBB, Nunes EC, Bittencourt RI, Rojas N, Truyenque SMQ, Ayala-Lugo AI, Oliver AC, Figueiredo-Pontes LL, Traina F, Moreira F, Fagundes EM, Duarte BKL, Mora-Alferez AP, Ortiz P, Untama JL, Tallman MS, Ribeiro RC, Ganser A, Dillon RJ, Valk PJM, Sanz MA, Lowenberg B, Berliner N, Rego EM. Early death and intracranial hemorrhage prediction in acute promyelocytic leukemia: validation of a risk score in a cohort from an international consortium treated with chemotherapy plus all-trans retinoic acid. Haematologica. 2025 Mar 1;110(3):795-798. doi: 10.3324/haematol.2024.286338. No abstract available.

Reference Type: BACKGROUND

PMID: 39479861 (View on PubMed)

Koury LCA, Kim HT, Undurraga MS, Navarro-Cabrera JR, Salinas V, Muxi P, Melo RAM, Gloria AB, Pagnano K, Nunes EC, Bittencourt RI, Rojas N, Quintana S, Ayala-Lugo A, Oliver AC, Figueiredo-Pontes L, Traina F, Moreira F, Fagundes EM, Duarte BKL, Mora-Alferez AP, Ortiz P, Untama J, Tallman M, Ribeiro R, Ganser A, Dillon R, Valk PJM, Sanz M, Lowenberg B, Berliner N, Rego EM. Clinical networking results in continuous improvement of the outcome of patients with acute promyelocytic leukemia. Blood. 2024 Sep 19;144(12):1257-1270. doi: 10.1182/blood.2024023890.

Reference Type: BACKGROUND

PMID: 38805638 (View on PubMed)

Correa de Araujo Koury L, Ganser A, Berliner N, Rego EM. Treating acute promyelocytic leukaemia in Latin America: lessons from the International Consortium on Acute Leukaemia experience. Br J Haematol. 2017 Jun;177(6):979-983. doi: 10.1111/bjh.14589. Epub 2017 May 3.

Reference Type: BACKGROUND

PMID: 28466545 (View on PubMed)

Rego EM, Kim HT, Ruiz-Arguelles GJ, Undurraga MS, Uriarte Mdel R, Jacomo RH, Gutierrez-Aguirre H, Melo RA, Bittencourt R, Pasquini R, Pagnano K, Fagundes EM, Chauffaille Mde L, Chiattone CS, Martinez L, Meillon LA, Gomez-Almaguer D, Kwaan HC, Garces-Eisele J, Gallagher R, Niemeyer CM, Schrier SL, Tallman M, Grimwade D, Ganser A, Berliner N, Ribeiro RC, Lo-Coco F, Lowenberg B, Sanz MA. Improving acute promyelocytic leukemia (APL) outcome in developing countries through networking, results of the International Consortium on APL. Blood. 2013 Mar 14;121(11):1935-43. doi: 10.1182/blood-2012-08-449918. Epub 2013 Jan 14.

Reference Type: BACKGROUND

PMID: 23319575 (View on PubMed)

Other Identifiers

1483/2019

Identifier Type: -

Identifier Source: org_study_id