A study to evaluate the safety and efficacy of oral decitabine plus ivosidenib in newly diagnosed adult patients with acute myeloid leukemia older than 60 years and/or inelegible for standard induction chemotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion PETHEMA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-02-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Otsuka Pharmaceutical S.A. · Servier Affires Médicales

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate safety and efficacy (CR/CRi rate) of IVO in combination with oral decitabine, in treatment naïve subjects equal or older than 60 years with acute myeloid leukemia (AML) and IDH1 mutation (or older than 18 with comorbidities precluding an intensive approach with IDH1 mutation).

Secondary objectives 11

1. To analyze overall survival (OS) and compare with a matched historical control cohort
2. To evaluate event-free survival (EFS) and compare with a matched historical control cohort
3. To evaluate composite complete remission (CR or CRi) after 2, 3 and 6 cycles, and compare with a matched historical control cohort
4. To evaluate global health status/quality of life (GHS/QoL) based on patient reported outcome (PRO) assessments.
5. To evaluate the impact on remaining subscales/items from the EORTC QLQ-C30 and EQ-5D-5L.
6. To assess the cumulative incidence of relapse and compare with a matched historical control cohort
7. To assess the overall hematologic and non-hematologic toxicity of experimental regimen
8. To evaluate the impact on the use of medical resources (ie, transfusions, duration of hospitalization)
9. To evaluate the quality of CR (by study of minimal residual disease percentages in the bone marrow using multiparametric flow cytometry and NGS)
10. To evaluate early mortality (first 60 days)
11. Exploratory: to assess MRD and clonal suppression by single cell analyses

Conditions and MedDRA coding

Acute myeloid leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Morphological diagnosis of AML (WHO criteria 2022)
2. Newly diagnosed AML
3. 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
4. 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
5. Age ≥ 18 years with comorbidities contraindicating intensive chemotherapy; or age ≥ 60 years
6. 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
7. Adequate renal function as demonstrated by a creatinine clearance ≥ 25 mL/min (calculated by the Cockcroft Gault formula)
8. 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)
9. Subject has a white blood cell count < 30 × 109/L (Hydroxyurea is permitted to meet this criterion)
10. 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
11. 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
12. 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 13

1. Subject has history of myeloproliferative neoplasm [MPN] with BCR-ABL1 translocation and AML with BCR-ABL1 translocation
2. Prior therapy for AML (except hydroxiurea)
3. Genetic diagnosis of acute promyelocytic leukemia
4. Subject is known to be positive for HIV (HIV testing is not required)
5. 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)
6. 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
7. Any severe uncontrolled systemic infection
8. 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
9. Creatinine clearance <25 mL/min (calculated by the Cockcroft-Gault formula)
10. 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)
11. 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
12. Contraindications for IVO or oral decitabine according to the SmPC
13. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete response (CR)/Immunophenotipic complete response (CRi), Safety

Secondary endpoints 1

1. Overall survival (OS), Event-free survival (EFS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion PETHEMA

Sponsor organisation

Fundacion PETHEMA

Address

Oficinas 3 4 5, Calle De Santa Balbina 2 Calle De Santa Balbina 2

City

Madrid

Postcode

28023

Country

Spain

Scientific contact point

Organisation

Fundacion PETHEMA

Contact name

Alfonso Santiago

Public contact point

Organisation

Fundacion PETHEMA

Contact name

Alfonso Santiago

Third parties 1

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications