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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• Overall Survival [Срок оценки: 2 years]

Вторичные конечные точки (8)

• Complete hematologic response rate after induction. [Срок оценки: 30 days]
• Early death rate during induction [Срок оценки: 30 days]
• Disease-free survival rate [Срок оценки: 2 years]
• Cumulative incidence of myelodysplasia and secondary leukemia [Срок оценки: 5 years]
• Cumulative incidence of relapse [Срок оценки: 2 years]
• Molecular remission rate after consolidation [Срок оценки: 150 days]
• PML/RARA transcript level during treatment [Срок оценки: Each 3 months]
• Days of hospitalization during treatment [Срок оценки: 180 days]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Бразилия · 1 центр

• Instituto do Cancer do Estado de Sao Paulo — São Paulo

Публикации

• 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 PMID 39479861
• 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 PMID 38805638
• 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. PMID 28466545
• 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 ac PMID 23319575

Идентификаторы

NCT: NCT06982274 · 1483/2019

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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