Study Investigating the Efficacy and Safety of the Addition of Oral-azacitidine to Salvage Treatment by Gilteritinib in Subjects ≥18 Years of Age With Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia
OGILAR
Open-label, Phase 2 Study Investigating the Efficacy and Safety of the Addition of Oral-azacitidine to Salvage Treatment by Gilteritinib in Subjects ≥18 Years of Age With Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia
2 other identifiers
interventional
33
1 country
20
Brief Summary
Approximately 30% of adult AML subjects are refractory to induction therapy. Furthermore, of those who achieve CR, approximately 75% will relapse. FLT3-mutated AML comprise an especially poor prognosis group. Until now, there was no established standard for relapsed subjects with FLT3 mutations and less than 20% will achieve CR with subsequent treatment. In phase 3 Study ADMIRAL Trial, gilteritinib has resulted in CRc in over 25% of subjects receiving 120 mg/day before on study HSCT. With this treatment, the median overall survival is at 9.3 months, furthermore, gilteritinib was well tolerated at the proposed doses. This study has been designed for R/R patients for which gilteritinib as single agent has been showed to be superior to high- and low-intensity chemotherapy (Perl, NEJM 2019, Supp Table S4) and patients included in this study will receive this treatment. Beyond high- or low-intensity chemotherapy, other options available are best supportive car or other clinical trials. The aim of this study is to assess the efficacy and safety of the addition of oral-azacitidine to salvage treatment by gilteritinib in subjects ≥18 years of age with relapsed/refractory FLT3-mutated acute myeloid leukemia
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jan 2024
Typical duration for phase_2
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 28, 2023
CompletedFirst Posted
Study publicly available on registry
September 1, 2023
CompletedStudy Start
First participant enrolled
January 13, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2027
March 24, 2025
March 1, 2025
2.7 years
August 28, 2023
March 20, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
characterize the rate of composite complete remission (CRc) as the best response to treatment during the first 3-months treatment
the rate of composite complete remission (CRc) \[defined by addition of complete remission (CR), complete remission with incomplete hematologic recovery (CRi), and complete remission with incomplete platelet recovery (CRp)\]
from inclusion to 3 months treatment
Secondary Outcomes (2)
characterize the Incidence and relatedness of adverse events (AE) and the percent of early death, with the combination of oral-azacitidine and gilteritinib
from inclusion and during treatment administration (median estimated is 6 months treatment)
characterize the rate of CR, rate of CRi, rate of CRp, rate of CRh
from inclusion to the first 6 months treatment
Study Arms (1)
Gilteritinib + Azacitidine oral (CC-486)
EXPERIMENTALGilteritinib 120 mg/day, PO by 28 days-cycle Azacitidine orale (CC-486) 300 mg/day, PO Day 1 to day 14, by 28 days-cycle
Interventions
AML study treatment
R/R FLT3-mutated AML standard treatment
Eligibility Criteria
You may qualify if:
- Confirmed diagnosis of acute myeloid leukemia (AML) according to world health organization (WHO) 2016 classification
- Subjects must be primary refractory or relapsed (R/R) to 1st line intensive chemotherapy (ICT) for AML. Hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis.
- a. Primary refractory is defined as no CR or CRi after at least one course of ICT (including "7+3", gemtuzumab ozogamycin (GO)-based and CPX-351, including or not midostaurine) or two courses (maximum 4) of AZA and venetoclax 3b. Relapse after 1st line ICT for AML is defined as the first hematologic relapse with bone marrow blasts \>5% after one line of treatment for AML that includes at least one course of ICT (one line of treatment for AML can include induction, re-induction, consolidation, allogeneic HSCT and maintenance) 3c. Relapse after 1st line non intensive chemotherapy for AML is defined as the first hematologic relapse with bone marrow blasts \>5% after or during treatment by AZA venetoclax regardless of number of cycles 4. 1st line intensive treatment may or may not include previous treatment by tyrosine kinase inhibitor (TKI) except gilteritinib.
- \. Patients who never received oral azacitidine 6. Age ≥ 18 years 7. Adequate baseline organ function defined by the criteria below:
- adequate renal function as demonstrated by a creatinine clearance ≥ 50 ml/min; calculated by the Cockcroft gault formula or measured by 24-hours urine collection
- aspartate aminotransferase (AST) ≤ 2.5 × ULN
- alanine aminotransferase (ALT) ≤ 2.5× ULN
- bilirubin ≤ 1.5 × ULN
- adequate cardiac function with LVEF ≥45% 8. ECOG \< 3 (appendix 1) 9. Absence of any psychological, familial, sociological, or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule 10. Patient is suitable for oral administration of study drug. 11. A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies: 9a. 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) 9b. WOCBP agrees to follow the contraceptive treatment starting at screening and continue throughout the study period, and for at least 180 days after the final study drug administration 12. Patient must be affiliated to the french social security (health insurance) 13. Signed written informed consent for the study 14. Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 60 days after the final study drug administration.
- \. Female subject must not donate ova starting at screening and throughout the study period, and for 180 days after the final study drug administration.
- \. A male subject with female partner(s) of childbearing potential must agree to use contraception starting at screening and continue throughout the study period, for at least 120 days after the final study drug administration.
- \. Male subject must not donate sperm starting at screening and throughout the study period and for 120 days after the final study drug administration.
You may not qualify if:
- \. Subjects with any of the following current or previous diagnoses:
- a. AML secondary to prior myeloproliferative syndrome (MPN)
- b. Acute promyelocytic leukemia (APL) and core binding factor (CBF) AML
- c. DNA fragility or bone marrow (BM) failure syndromes
- d. Blastic plasmacytoid dendritic cell neoplasm
- e. Acute lymphoblastic leukemia including ambiguous lineage 2. Patients ≥ 3rd line of treatment, HSCT being not considered as a line of treatment 3. Patients previously treated by AZA as single agent for AML are not allowed 4. Subjects that have previously been treated by gilteritinib 5. Subjects that have previously been treated by oral azacitidine 6. Clinically active central nervous system (CNS) leukemia 7. Subjects who have received more than 1 prior allogeneic HSCT 8. Subjects who have relapsed within 100 days after allogeneic HSCT 9. Presence of Grade 2 or above graft-versus-host disease (GVHD), including acute, chronic, or overlap; or escalation of therapy for GVHD within 14 days prior to randomization 10. Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A (Annexe 7) 11. Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P-gp with the exception of drugs that are considered absolutely essential for the care of the subject (Annexe 7) 12. Severe liver disease (e.g. cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis or hyperbilirubinemia) 13. Participant has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation (DIC).
- \. Subject exhibiting evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
Amiens CHU
Amiens, France
Angers CHU
Angers, France
Hôpital d'Instruction des Armées PERCY
Clamart, France
CHU Estaing
Clermont-Ferrand, France
Créteil CHU HENRI MONDOR
Créteil, France
Grenoble CHU
Grenoble, France
CHU Lille
Lille, France
Limoges CHU
Limoges, France
Lyon sud CHU
Lyon, France
Marseille IPC
Marseille, France
Nantes CHU
Nantes, France
Centre Antoine Lacassagne
Nice, France
Paris Saint Louis
Paris, France
Bordeaux CHU
Pessac, France
Rennes CHU
Rennes, France
Centre de Lutte Contre le Cancer H. Becquerel
Rouen, France
ICANS - Institut de cancérologie de strasbourg europe
Strasbourg, France
Toulouse - IUCT Oncopole - Service d'Hématologie
Toulouse, France
Nancy CHU
Vandœuvre-lès-Nancy, France
Versailles CH
Versailles, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
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
August 28, 2023
First Posted
September 1, 2023
Study Start
January 13, 2024
Primary Completion (Estimated)
October 1, 2026
Study Completion (Estimated)
October 1, 2027
Last Updated
March 24, 2025
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will not share