FILO-AML-01-MIVONU 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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

French Innovative Leukemia Organization

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2025-11-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy, Therapy

Evaluate relapse free survival (RFS) at 24 months in patients receiving oral azacitidine with ivosidenib.

Secondary objectives 4

1. Evaluate RFS at 12 months in patients receiving oral azacitidine with ivosidenib
2. Evaluate overall survival (OS) at 12 and 24 months in patients receiving oral azacitidine with ivosidenib
3. Evaluate MRD-negative Event-Free Survival (EFSMRD) at 3, 6, 12 and 24 months
4. Describe the Treatment Emergent Adverse Events (TEAEs)

Conditions and MedDRA coding

Patients over 55 with Acute Myeloid Leukemia (AML) and IDH1 mutation, in complete remission after intensive chemotherapy.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Male or female ≥ 55 years of age at the time of signing informed consent
2. Patients with confirmation of newly diagnosed AML by 2022 WHO criteria
3. Presence of IDH1 R132 mutation at AML diagnosis
4. Achievement CR or CRi following induction therapy by intensive chemotherapy (according to ELN 2022), within 17 weeks prior to enrollment.
5. Received at least 2 consolidations : a. with intermediate dose of cytarabine (IDAC); b. or with standard dose cytarabine and idarubicin (5+1)
6. Adequate BM function: ANC ≥1 × 109/L and platelet count ≥50 × 109/L at the time of inclusion
7. Patients who are not candidate for Allo-HSCT
8. Adequate baseline organ function defined by the following criteria: - Estimated Glomerular Filtration Rate (eGFR) ≥ 30 ml/min (using CKD-EPI); - aspartate aminotransferase (AST) ≤ 2.5 × ULN ; - alanine aminotransferase (ALT) ≤ 2.5× ULN ; - bilirubin ≤ 1.5 × ULN
9. ECOG < 3
10. Absence of any psychological, familial, sociological, or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule
11. Patient suitable for oral administration of study drug.
12. A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in post-menopausal (defined as at least 1 year without any menses) prior to Screening, or documented as surgically sterile (at least 1 month prior to Screening); b. WOCBP agrees to follow the contraceptive treatment starting at screening and continued throughout the study period, and for at least 180 days after the final study drug administration; c. WOCBP agrees to perform planned pregnancy tests in the study
13. Female subject must agree not to breastfeed starting at screening and throughout the study period, and for one month after the final study drug administration.
14. Female subject must not donate ova starting at screening and throughout the study period, and for 180 days after the final study drug administration.
15. A male subject with a partner(s) of childbearing potential must agree to use contraception starting at screening and continue throughout the study period, for at least 90 days after the final study drug administration.
16. A male subject must not donate sperm starting at screening nor throughout the study period and for 90 days after the final study drug administration
17. Patient must be affiliated to the French social security (health insurance)
18. Signed written informed consent for the study

Exclusion criteria 19

1. Acute promyelocytic leukemia (FAB M3) with t(15;17) or its molecular equivalents (PML::RARA)
2. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
3. Severe medical or mental condition precluding the administration of protocol treatments
4. Persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure (guardianship, curatorship, legal protection), persons under psychiatric care
5. Other comorbidity that the physician judges to be incompatible with the study design
6. Any condition causing an inability to swallow tablets or known hypersensitivity to the study medication
7. Any condition that would impair absorption of the study medication (i.e. short gut, malabsorption syndrome)
8. Subject requiring treatment with concomitant drugs that are strong inducers/inhibitors of cytochrome P450 (CYP)3A /PGP or dabigatran (PGP substrate) (see appendix 6) or QT-prolongating agent other than 5-HT3 antagonists (see appendix 8) or other forbidden medications listed in section 10.7.
9. Subject with positive HIV test treated or planned to be treated with drugs with potential drug-drug interactions. HIV testing will be performed at screening, if required per local guidelines or institutional standards.
10. Subject known to be positive for hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status with undetectable PCR viral load on antivirals (non-exclusionary medications) are not excluded.
11. AML associated with t(9;22) or molecular evidence of such a translocation
12. Prior BM or hematopoietic stem cell transplantation
13. CR/CRi following treatment with hypomethylating agents
14. Proven central nervous system leukemia
15. Candidate for Allo-HSCT at screening
16. Diagnosis of malignant disease within the previous 12 months (excluding MDS or CMML, basal cell carcinoma of the skin without complications, “in- situ” carcinoma of the cervix or breast, or other local malignancy excised or irradiated with a high probability of cure)
17. Abnormal cardiac status with any of the following: - Unstable angina ; - Myocardial infarction within the last 6 months ; - Significant cardiac arrhythmia ; - New York Heart Association (NYHA) class 3 or 4 congestive heart failure ; - Congenital long QT syndrome, familial history of sudden death or polymorphic ventricular arrhythmias and QT/QTc interval > 500 msec regardless of the correction method. For subject with 450 ≤ QTc ≤ 500 ms, practitioners should thoroughly reassess the benefit/risk of initiating ivosidenib. In case QTc interval prolongation is between 480 msec and 500 msec, initiation of treatment with ivosidenib should remain exceptional and be accompanied by close monitoring. This issue will be discuss with coordinating investigator.
18. Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)
19. Subject with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Relapse-free-survival (RFS) at 24 months in patients receiving oral azacitidine with ivosidenib.

Secondary endpoints 4

1. RFS at 12 months, with the same definition for RFS as for the primary endpoint.
2. Overall survival defined as the time between inclusion assignment and death from any cause, at 12 and 24 months. Patients alive will be censored at the date of last news, or data cutoff.
3. EFS MRD-, defined in patients who were MRD negative at baseline as the time from inclusion to MRD relapse (by FCM or RT-qPC for NPM1) or death from any cause, whichever occurred first. Patients alive without MRD relapse will be censored at the date of last MRD assessment.
4. Number of participants with Treatment Emergent Adverse Events (TEAEs), according the CTCAE v5.0 classification.

Investigational products

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

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

French Innovative Leukemia Organization

Sponsor organisation

French Innovative Leukemia Organization

Address

2 Boulevard Tonnelle

City

Tours

Postcode

37000

Country

France

Scientific contact point

Organisation

French Innovative Leukemia Organization

Contact name

Pr Arnaud PIGNEUX

Public contact point

Organisation

French Innovative Leukemia Organization

Contact name

FILO desk officer

Third parties 7

Locations

1 EU/EEA country · 20 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 11 files

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

Application history

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