Oral Decitabine Plus Ivosidenib as First Line for Older/Unfit Adult AML Patients

NCT07507760 | Not Yet Recruiting Phase 2

• 1 other identifier: DECISIVO
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 15

Brief Summary

The goal of this clinical trial is to learn if the combination of oral decitabine plus ivosidenib works to treat naïve adult patients with acute myeloid leukemia (AML) with IDH1 R132 mutation older than 60 years old or those who are older than 18 years old with defined comorbidities that make them not suitable for standard induction therapy. The main objectives of this clinical trial are:

• Asses the Complete Remission (CR) and Complete Remission with incomplete marrow recovery (CRi) rates of this treatment.
• Determine the incidence and severity of all adverse events (AEs). All participants will receive oral ivosidenib and oral decitabine in treatment cycles of 28 days until disease progression, lack of clinical benefit or the end of the study. Patients who achieve CR/CRi will be elegible to receive allogeneic stem cell transplantation.

Conditions

Acute Myeloid Leukemia With Gene Mutations

Keywords

AML; older adult; unfit; IDH1 R132 mutation; Decitabine; Ivosidenib; allogeneic stem cell transplant

Outcome Measures

Primary Outcomes (1)

• Rate of CR/CRi

  To assess the rates of Complete Remission (CR) and Complete Remission with incomplete marrow recovery (CRi) of participants treated with Ivosidenib plus Decitabine

  3 years

Secondary Outcomes (6)

• Rate CR/CRi compared to historical cohort

  3 years

• OS compared to historical cohort

  3 years

• EFS compared to historical cohort

  3 years

• Hematologic and non-hematologic toxicity and AE

  3 years

• Quality of CR

  3 years

Study Arms (1)

Decitabine+Ivosidenib

EXPERIMENTAL

Participants will receive treatment cycles of 28 days with Ivosidenib 500 mg/orally on Days 1-28 plus oral decitabine-cedazuridine (one tablet once daily containing 35 mg decitabine and 100 mg cedazuridine as a fixed-dose combination) on days 1-5. Hydroxiurea or maximum 1 gram/sqm of cytarabine is allowed to control hyperleukocytosis during the screening period as well as during the first two cycles of induction. Participants who achieve CR/CRi can be submitted to allogeneic stem cell transplant and will be allowed to resume ivosidenib after day +60 of transplant. The post-transplant schedule can be administered for up to 2 years.

Drug: Decitabine/Cedazuridine 35 Mg-100 Mg ORAL TABLET; Drug: Ivosidenib Oral Tablet; Drug: Hydroxyurea; Drug: Cytarabine; Procedure: Allogeneic stem cell transplantation

Interventions

Decitabine/Cedazuridine 35 Mg-100 Mg ORAL TABLET DRUG

Oral Decitabine (Decitabine/Cedazuridine 35 Mg-100 Mg) will be administerd on Days 1-5 of each treatment cycle

Decitabine+Ivosidenib

Ivosidenib Oral Tablet DRUG

Ivosidenib 500 mg/orally on Days 1-28 of each treatment cycle

Decitabine+Ivosidenib

Hydroxyurea DRUG

0.5-6 gram/day orally during the screening period and the two first treatment cycles if hyperleukocytosis at diagnosis

Decitabine+Ivosidenib

Cytarabine DRUG

Maximum 1 gram/sqm/day during the screening period and the two first treatment cycles if hyperleukocytosis at diagnosis

Decitabine+Ivosidenib

Allogeneic stem cell transplantation PROCEDURE

Only for those participants achieving CR/CRi

Decitabine+Ivosidenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ≥ 60 years of age;
• or ≥ 18 to 60 with at least one of the following co-morbidities:
• ECOG Performance Status of 2 or 3;
• Cardiac history of CHF requiring treatment or Ejection Fraction ≤ 55% or chronic stable angina;
• DLCO ≤ 65% or FEV1 ≤ 65% or significant history of chronic pulmonary obstructive;
• Creatinine clearance ≥ 25 mL/min to \< 50 ml/min
• Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 × ULN
• Non active/controlled prior neoplastic disease
• Any other patient´s comorbidity or disease condition that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the PETHEMA medical monitor before study enrolment (e.g, prior MDS or MPS, high-risk cytogenetics)
• 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.

You may not qualify if:

• 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, in which case it should be approved by the PETHEMA medical monitor)
• 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.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (15)

Complejo Hospitalario de Albacete

Albacete, 02006, Spain

Location

Hospital General Universitario Dr. Balmis

Alicante, Spain

Location

Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Hospital San Pedro Alcántara

Cáceres, Spain

Location

Complejo Hospitalario Regional Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario de Gran Canaria Doctor Negrín

Las Palmas, Spain

Location

Hospital Universitario de Canarias

Las Palmas de Gran Canaria, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

H. 12 de Octubre

Madrid, Spain

Location

Hospital Univeristario Ramón y Cajal

Madrid, Spain

Location

Hospital Virgen de la Victoria

Málaga, Spain

Location

Hospital Universitario Virgen Del Rocío

Seville, Spain

Location

H. Dr. Peset

Valencia, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, Spain

Location

MeSH Terms

Interventions

Decitabine; cedazuridine; ivosidenib; Hydroxyurea; Cytarabine

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Urea; Amides; Arabinonucleosides

Study Officials

• Pau Montesinos

  Hospital Universitari i Politèncic La Fe

  STUDY CHAIR

Central Study Contacts

Pau Montesinos

CONTACT

+34 96 1244925; montesinos_pau@gva.es

Juan José Lahuerta

CONTACT

jjlahuerta@telefonica.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2026
• First Posted: April 2, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (15)