Ignite Creation Date:
2026-03-26 @ 3:16 PM
Ignite Modification Date:
2026-03-30 @ 2:25 AM
Study NCT ID:
NCT07463768
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-11
First Post:
2026-02-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study Evaluating the Efficacy and Safety of the Addition of Ivosidenib to Oral Azacitidine (Onureg®) in Patients Over 55 With Acute Myeloid Leukemia (AML) and IDH1 Mutation, in Complete Remission After Intensive Chemotherapy.
Sponsor:
French Innovative Leukemia Organisation
Organization:
Study Overview
Official Title:
A Single Arm Phase II Study Investigating the Efficacy and Safety of the Addition of Ivosidenib to Oral Azacitidine (Onureg®) in Patients Over 55 With Acute Myeloid Leukemia (AML) and IDH1 Mutation, in Complete Remission After Intensive Chemotherapy. A Study of the French AML Intergroup.
Status:
NOT_YET_RECRUITING
Status Verified Date:
2026-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MIVONU
Brief Summary:
After remission post-induction and consolidation, maintenance therapy by an ivosidenib and oral azacitidine combination is susceptible to improve the prevention of AML relapse, which remains a major issue in the study population. We assume that the combination of ivosidenib with oral azacitidine will not be less well tolerated than in combination with the subcutaneous form, therapeutic regimen authorized until progression or toxicity. Ivosidenib and Onureg®, being already authorized treatments, it has been decided to use the classic administration schedules and dosages in combination.
The primary objective of the study is to evaluate relapse free survival (RFS) at 24 months in patients receiving oral azacitidine with ivosidenib.
The primary objective of the study is to evaluate relapse free survival (RFS) at 24 months in patients receiving oral azacitidine with ivosidenib.
Detailed Description:
According to data from the Institut de Veille Sanitaire, the frequency of Acute Myeloid Leukemia (AML) is about 3 cases per 100,000 inhabitants, a frequency which increases with age to reach 20 / 100,000 at 70 years. AML is characterized by recurrent molecular and cytogenetic abnormalities. Among mutations arising with age, those of IDH1 (isocitrate dehydrogenase 1) and IDH2 ((isocitrate dehydrogenase 2) are considered as early molecular events driving AML transformation, characterized by a DNA hypermethylation signature. Somatic mutations in the gene encoding IDH1 occur in 6 to 16% of patients with AML.
In intensively treated (ICT) patients, IDH1 mutations are associated with a poorer outcome in patients treated with ICy34, even in case of favorable-ELN risk. Hematopoietic stem cell transplantation (HSCT) for IDH1mut patients in CR1 after ICT drastically improves OS (HR, 0.48; P = .048). However, in real life settings, and more specifically in elderly patients, only 40% of patients with HSCT indication are effectively transplanted.
For patients who are not candidates for HSCT, effective AML maintenance therapies are needed that can reduce the risk of relapse and prolong overall survival without causing undue adverse effects or compromising health-related quality of life. Indeed, relapse rates after IC without HSCT remain high with limited therapeutic options in this setting. There is a clear unmet medical need to improve the outcome of patients treated with IC who are not candidate for HSCT.
Oral azacitidine is approved as maintenance therapy in adult AML patients who achieve CR or CR without blood count recovery (CRi), following induction therapy and are not eligible for allo-HCT. Nevertheless, according to results of the pivotal QUAZAR-AML-001 placebo-controlled trial, estimated 5-year overall survival reached only 26% in the oral azacitidine arm versus 20% in the placebo arm.
Ivosidenib, a first-in-class, oral, potent, targeted small-molecule inhibitor of mutant IDH1, has shown clinical activity as a single agent in studies involving patients with hematologic and solid-tumors. In a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated relapsed or refractory AML, the rate of CR or CRi was 30,4%.
For newly diagnosed patients with IDH1 mutation, results from a randomized study (AGILE trial) indicate that the IDH1 inhibitor ivosidenib plus azacitidine improves event-free survival (EFS) (hazard ratio, 0.33; 95% CI, 0.16-0.69), clinical response (CR/CRh, 52.8 vs 17.6%), and median OS (29.3 vs 7.9 months) compared with azacitidine plus placebo.
After remission post-induction and consolidation, maintenance therapy by an ivosidenib and oral azacitidine combination is susceptible to improve the prevention of AML relapse, which remains a major issue in the study population. We assume that the combination of ivosidenib with oral azacitidine will not be less well tolerated than in combination with the subcutaneous form, therapeutic regimen authorized until progression or toxicity. Ivosidenib and Onureg®, being already authorized treatments, it has been decided to use the classic administration schedules and dosages in combination
In intensively treated (ICT) patients, IDH1 mutations are associated with a poorer outcome in patients treated with ICy34, even in case of favorable-ELN risk. Hematopoietic stem cell transplantation (HSCT) for IDH1mut patients in CR1 after ICT drastically improves OS (HR, 0.48; P = .048). However, in real life settings, and more specifically in elderly patients, only 40% of patients with HSCT indication are effectively transplanted.
For patients who are not candidates for HSCT, effective AML maintenance therapies are needed that can reduce the risk of relapse and prolong overall survival without causing undue adverse effects or compromising health-related quality of life. Indeed, relapse rates after IC without HSCT remain high with limited therapeutic options in this setting. There is a clear unmet medical need to improve the outcome of patients treated with IC who are not candidate for HSCT.
Oral azacitidine is approved as maintenance therapy in adult AML patients who achieve CR or CR without blood count recovery (CRi), following induction therapy and are not eligible for allo-HCT. Nevertheless, according to results of the pivotal QUAZAR-AML-001 placebo-controlled trial, estimated 5-year overall survival reached only 26% in the oral azacitidine arm versus 20% in the placebo arm.
Ivosidenib, a first-in-class, oral, potent, targeted small-molecule inhibitor of mutant IDH1, has shown clinical activity as a single agent in studies involving patients with hematologic and solid-tumors. In a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated relapsed or refractory AML, the rate of CR or CRi was 30,4%.
For newly diagnosed patients with IDH1 mutation, results from a randomized study (AGILE trial) indicate that the IDH1 inhibitor ivosidenib plus azacitidine improves event-free survival (EFS) (hazard ratio, 0.33; 95% CI, 0.16-0.69), clinical response (CR/CRh, 52.8 vs 17.6%), and median OS (29.3 vs 7.9 months) compared with azacitidine plus placebo.
After remission post-induction and consolidation, maintenance therapy by an ivosidenib and oral azacitidine combination is susceptible to improve the prevention of AML relapse, which remains a major issue in the study population. We assume that the combination of ivosidenib with oral azacitidine will not be less well tolerated than in combination with the subcutaneous form, therapeutic regimen authorized until progression or toxicity. Ivosidenib and Onureg®, being already authorized treatments, it has been decided to use the classic administration schedules and dosages in combination
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: