Acute Promyelocytic Leukemia (APL)Phase 2IC-APL2020NCT06982274
Oral Arsenic With ATRA for Newly Diagnosed Patients With Acute Promyelocytic Leukemia
A Phase 2 study testing Realgar-Indigo Naturalis Formulation in people with Acute Promyelocytic Leukemia (APL), run by Instituto do Cancer do Estado de São Paulo at 1 site in Brazil.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Promyelocytic Leukemia (APL)
- What is being tested?
- Realgar-Indigo Naturalis Formulation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 115 participants
- Where
- 1 siteBrazil
- Study dates
- 20 Oct 2023to Nov 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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%)
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Instituto do Cancer do Estado de Sao Paulo
São Paulo, São Paulo, 01246000
Wellington Silva, MD PhD, 55 11 38934144, wellington.fernandes@hc.fm.usp.br
Rodrigo Bonardi, MD, 55 11 38934144, rodrigo.bonardi@hc.fm.usp.br
About this study
Official title: 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
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.
Read the 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)
- Being tested
- Realgar-Indigo Naturalis Formulation
- Keywords
- Acute promyelocytic leukemia, Oral arsenic, Survival, All trans-retinoic acid
- Medical subject headings
- Leukemia, Promyelocytic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Realgar-Indigo Naturalis FormulationDrug
Also called Oral Arsenic
Oral Arsenic (Realgar-Indigo Naturalis Formulation) plus ATRA for low-intermediate risk APL pts, combined with daunorubicin for high-risk during induction
| Study group | Role | What they receive |
|---|---|---|
| Proposed protocol | Experimental | Oral Arsenic + ATRA with low-dose daunorubicin for high-risk patients Receives: Drug: Realgar-Indigo Naturalis Formulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
This endpoint includes death from any cause, including early death, death due to disease progression, or any death occurring after achieving complete remission.
Measured: 2 years
Secondary outcomes (8)
Complete hematologic response rate after induction.
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.
Measured: 30 days
Early death rate during induction
Death before blood cell counts recovery during induction.
Measured: 30 days
Disease-free survival rate
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.
Measured: 2 years
Cumulative incidence of myelodysplasia and secondary leukemia
The proportion of patients who develop myelodysplastic syndromes or secondary leukemia after treatment.
Measured: 5 years
Cumulative incidence of relapse
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.
Measured: 2 years
Molecular remission rate after consolidation
The proportion of patients who achieve a negative molecular test by PCR for PML-RARA after completing the consolidation phase of treatment.
Measured: 150 days
PML/RARA transcript level during treatment
The quantitative measurement of the PML/RARA fusion gene transcript, assessed by PCR, at various stages of therapy.
Measured: Each 3 months
Days of hospitalization during treatment
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.
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2025
- Study start20 Oct 2023
- Primary completionNov 2028 (estimated)
- Study completionNov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Acute Promyelocytic Leukemia (APL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 115 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto do Cancer do Estado de São Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- American Society of Hematology
- Responsible party
- Sponsor
- Investigators
- Eduardo M Rego, MD PhD, Principal investigator, Instituto do Cancer do Estado de Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06982274
- Sponsor's protocol ID
- 1483/2019
- Acronym
- IC-APL2020
- Status last verified
- May 2025
- First submitted
- 13 May 2025
- Last updated
- 30 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39479861Koury 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.
PubMed 38805638Correa 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.
PubMed 28466545Rego 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.
PubMed 23319575