Efficacy and Safety of Oral Decitabine and Ivosidenib in Adults with Newly Diagnosed IDH1-Mutated Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy
- Trial ID
- 2025-523238-17-00
- Protocol
- DECISIVO
- Sponsor
- Fundacion PETHEMA
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the efficacy and safety of oral decitabine combined with ivosidenib in treatment-naïve patients with acute myeloid leukemia harboring an IDH1 mutation. This population includes adults aged 60 years or older, as well as patients of any age with comorbidities precluding intensive induction chemotherapy. Efficacy is specifically measured by the rate of complete remission or complete remission with incomplete hematologic recovery. Secondary objectives include:
- Comparison of overall survival and event-free survival against a matched historical control cohort.
- Assessment of the composite complete remission rate following 2, 3, and 6 treatment cycles.
- Evaluation of the cumulative incidence of relapse.
- Analysis of minimal residual disease in the bone marrow via multiparametric flow cytometry and next-generation sequencing to determine the quality of remission, including exploratory clonal suppression via single-cell analyses.
- Monitoring of hematologic and non-hematologic toxicity, as well as early mortality within the first 60 days.
- Measurement of quality of life and global health status using patient-reported outcomes, specifically the EORTC QLQ-C30 and EQ-5D-5L instruments.
- Evaluation of medical resource utilization, such as hospitalization duration and transfusion requirements.
Participants
The sponsor did not provide the total number of participants. The study population consists of patients with acute myeloid leukemia (AML) harboring an IDH1 mutation. Eligible individuals include those aged 60 years or older, or those aged 18 to 59 years with comorbidities that preclude an intensive therapeutic approach. Participants must meet WHO criteria for a morphological diagnosis of AML. Requirements include an ECOG performance status between 0 and 2 for individuals aged 60 and older, or between 0 and 3 for those aged 18 to 60. Specific clinical parameters include a white blood cell count of less than 30 × 10⁹/L and adequate renal function, defined by a creatinine clearance of at least 25 mL/min. Additionally, liver function must be within specified limits regarding aspartate aminotransferase, alanine aminotransferase, and bilirubin levels. For patients under 70 years of age with favorable risk AML, inclusion is restricted to those who are not candidates for standard intensive chemotherapy. Female participants must be postmenopausal, surgically sterile, or utilize specific contraception methods. The study includes both male and female subjects.
Plans and Procedures
This phase II, multicentre, open-label clinical trial is designed to evaluate the efficacy and safety of oral decitabine combined with ivosidenib. The study focuses on adult patients with newly diagnosed acute myeloid leukemia harboring IDH1 mutations. The primary efficacy endpoint is the rate of complete response (CR) or immunophenotypic complete response (CRi), while secondary endpoints include overall survival and event-free survival. The research methodology involves an initial screening period to confirm morphological diagnosis, mutation status, and eligibility based on ECOG performance status and organ function. Following screening, participants receive the study medication, with subsequent monitoring to assess safety and therapeutic response. The overall trial is estimated to continue through March 2030.
Treatment
The experimental treatment consists of ivosidenib, administered as 500 mg film-coated tablets via an oral route. This medication is intended for patients with acute myeloid leukemia harboring an IDH1 mutation.
The study also utilizes a combination therapy involving decitabine and cedazuridine, provided as Inaqovi 35 mg/100 mg film-coated tablets. The total daily dose of this combination is 135 mg, administered orally.
Efficacy
The efficacy of the combination of ivosidenib and oral decitabine will be assessed in patients with acute myeloid leukemia. The primary efficacy endpoints are the rates of complete response (CR) and immunophenotypic complete response (CRi).
Secondary efficacy endpoints include overall survival (OS) and event-free survival (EFS).
Inclusion and Exclusion Criteria
Inclusion Criteria
- Morphological diagnosis of AML (WHO criteria 2022)
- Newly diagnosed AML
- IDH1 R132 mutations (centrally assessed by PCR and NGS). A patient will be allowed to be included with local result after approval of the medical monitor
- Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2 if ≥ 60 years of age, or 0 to 3 if ≥ 18 to 60 years
- Age ≥ 18 years with comorbidities contraindicating intensive chemotherapy; or age ≥ 60 years
- Patients <70 years, with favorable risk AML according to ELN will be included only if they are not candidates to standard treatment with intensive chemotherapy
- Adequate renal function as demonstrated by a creatinine clearance ≥ 25 mL/min (calculated by the Cockcroft Gault formula)
- Adequate liver function as demonstrated by: aspartate aminotransferase (AST) ≤ 5.0 × ULN, alanine aminotransferase (ALT) ≤ 5.0 × ULN, bilirubin ≤ 2.5 × ULN (unless considered to be due to leukemic disease)
- Subject has a white blood cell count < 30 × 109/L (Hydroxyurea is permitted to meet this criterion)
- Female subjects must be either postmenopausal OR permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy) OR Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control. Female subjects of childbearing potential must have negative results for pregnancy test performed
- Male subjects who are sexually active, must agree, from Study Day 1 through at least 90 days after the last dose of study drug, to practice the protocol specified contraception
- Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures
Exclusion Criteria
- Subject has history of myeloproliferative neoplasm [MPN] with BCR-ABL1 translocation and AML with BCR-ABL1 translocation
- Prior therapy for AML (except hydroxiurea)
- Genetic diagnosis of acute promyelocytic leukemia
- Subject is known to be positive for HIV (HIV testing is not required)
- Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. (Hepatitis B or C testing is not required)
- Subject has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition or known hypersensitivity to any of the study medications including excipients that in the opinion of the investigator would adversely affect his/her participating in this study
- Any severe uncontrolled systemic infection
- Subject has a history of other malignancies within 1 year prior to study entry which is not controlled and/or requiring active therapy which may compromise the administration of IVO and oral decitabine
- Creatinine clearance <25 mL/min (calculated by the Cockcroft-Gault formula)
- Inadequate liver function as demonstrated by AST or ALT > 5.0 × ULN, or bilirubin > 2.5 × ULN (unless considered to be due to leukemic disease)
- Subject has a white blood cell count > 30 × 109/L that is not controlled using hydrea or 1 gr/sqm/day per 1 day of cytarabine
- Contraindications for IVO or oral decitabine according to the SmPC
- Patient has a heart rate-corrected QT interval using Fridericia’s method QT for corrected heart rate (QTcF) ≥450 msec or any other factor that increases the risk of QT prolongation or arrhythmic events (e.g., hypokalemia, family history of long QT interval syndrome). Patients with prolonged QTcF interval in the setting of bundle branch block may participate in the trial
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 25 Mar 2026 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Inaqovi 35 mg/100 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 135 | 36 | PRD10840060 |
Tibsovo 250 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 500 | 36 | PRD10392230 |