Trouver des essais cliniques
Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Participants With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation (AGILE)
Code de protocole Servier:
AG120-C-009
Sponsor:
Institut de Recherches Internationales Servier
Identifiant Clinicaltrials.gov:
NCT03173248
Trouver un site de recrutement
Comment participer à cette étude
Si vous pensez être éligible pour cette étude (voir
ci-dessous), vous pouvez identifier le site le plus proche de chez vous et le contacter directement. Si vous ne trouvez pas de site près de chez vous, veuillez contacter l'Institut de Recherches Internationales Servier (I.R.I.S.).
critères d'éligibilité
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Ceux-ci comprennent les critères d'inclusion et les critères d'exclusion. Parmi ces critères, on peut citer l'état de santé général d'une personne ou les traitements antérieurs qu'elle a suivis.
Nom:
Institut de Recherches Internationales Servier, Département des études cliniques
Numéro de téléphone:
+33 1 55 72 60 00
L'étude a 90 centres
Description de l'étude
Study AG120-C-009 is a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of AG-120 (ivosidenib) + azacitidine vs placebo + azacitidine in adult participants with previously untreated IDH1m AML who are considered appropriate candidates for non-intensive therapy. The primary endpoint is event-free survival (EFS). The key secondary efficacy endpoints are overall survival (OS), rate of complete remission (CR), rate of CR and complete remission with partial hematologic recovery (CRh), and overall response rate (ORR). Participants eligible for study treatment based on Screening assessments will be randomized 1:1 to receive oral AG-120 or matched placebo, both administered in combination with subcutaneous (SC) or intravenous (IV) azacitidine. An estimated 200 participants will take part in the study.
Titre officiel: A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of AG-120 in Combination With Azacitidine in Subjects ≥ 18 Years of Age With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation
Indications
Newly Diagnosed Acute Myeloid Leukemia (AML)
Untreated AML
AML Arising From Myelodysplastic Syndrome (MDS)
Leukemia, Myeloid, Acute
Interventions / Traitements
Le ou les traitements administrés aux participants à l'étude.
- AG-120
- Placebo
- Azacitidine
Autres numéros d'identification
Autres numéros d'identification sous lesquels l'étude peut être connue.
- AG120-C-009
Critères d'éligibilité
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Ceux-ci comprennent les critères d'inclusion et les critères d'exclusion. Parmi ces critères, on peut citer l'état de santé général d'une personne ou les traitements antérieurs qu'elle a suivis.
Age éligible pour l’étude
18 ans et plus
(Adulte, Adulte plus âgé)
Sexe
Homme/FemmeAccepte les volontaires en bonne santé
Non- 1. Be ≥ 18 years of age and meet at least 1 of the following criteria defining ineligibility for intensive induction chemotherapy (IC): ≥ 75 years old, Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 2, severe cardiac disorder (e.g., congestive heart failure requiring treatment, left ventricular ejection fraction (LVEF), ≤50%, or chronic stable angina), severe pulmonary disorder (e.g., diffusing capacity of the lungs for carbon monoxide ≤65% or forced expiratory volume in 1 second ≤65%), creatinine clearance <45 mL/minute, bilirubin >1.5 times the upper limit of normal (ULN) and/or have any other comorbidity that the Investigator judges to be incompatible with intensive IC and must be reviewed and approved by the Medical Monitor before study enrollment.
- 2. Have previously untreated AML, defined according to World Health Organization (WHO) criteria, with ≥ 20% leukemic blasts in the bone marrow. Participants with extramedullary disease alone (i.e., no detectable bone marrow and no detectable peripheral blood AML) are not eligible for the study.
- 3. Have an isocitrate dehydrogenase 1 (IDH1) mutation.
- 4. Have an ECOG PS score of 0 to 2.
- 5. Have adequate hepatic function.
- 6. Have adequate renal function.
- 7. Have agreed to undergo serial blood and bone marrow sampling.
- 8. Be able to understand and willing to sign an informed consent form (ICF).
- 9. Be willing to complete Quality of Life assessments during the study
- 10. If female with reproductive potential, must have a negative serum pregnancy test prior to the start of study therapy. Females of reproductive potential, as well as fertile men and their female partners of reproductive potential, must agree to use 2 effective forms of contraception.
- 1. Are candidates for and willing to receive intensive induction chemotherapy (IC) for their AML.
- 2. Have received any prior treatment for AML with the exception of hydroxyurea.
- 3. Have received a hypomethylating agent for myelodysplastic syndrome (MDS).
- 4. Participants who had previously received an experimental agent for MDS may not be randomized until a washout period has elapsed since the last dose of that agent.
- 5. Have received prior treatment with an IDH1 inhibitor.
- 6. Have a known hypersensitivity to any of the components of AG-120, matched placebo, or azacitidine.
- 7. Are female and pregnant or breastfeeding.
- 8. Have an active, uncontrolled, systemic fungal, bacterial, or viral infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.
- 9. Have a prior history of cancer other than MDS or myeloproliferative disorder, unless the participant has been free of the disease for ≥ 1 year prior to the start of study treatment.
- 10. Have had significant active cardiac disease within 6 months prior to the start of the study treatment.
- 11. Have any condition that increases the risk of abnormal ECG or cardiac arrhythmia.
- 12. Have a condition that limits the ingestion or absorption of drugs administered by mouth.
- 13. Have uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or diastolic BP > 100 mmHg).
- 14. Have clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia.
- 15. Have immediate, life-threatening, severe complications of leukemia, such as uncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminated intravascular coagulation.
- 16. Have any other medical or psychological condition deemed by the Investigator to be likely to interfere with the participant's ability to give informed consent or participate in the study.
- 17. Are taking medications that are known to prolong the QT interval unless they can be transferred to other medications within ≥5 half-lives prior to dosing, or unless the medications can be properly monitored during the study. (If equivalent medication is not available, heart rate corrected QT interval [QTc] will be closely monitored.)
- 18. Have a known medical history of progressive multifocal leukoencephalopathy.
Comment l'étude est-elle conçue ?
Allocation
Comment les participants sont répartis dans différents groupes. La répartition peut être aléatoire (randomisée) ou prédéterminée (non randomisée). Randomisée signifie que les participants sont répartis de manière aléatoire dans leur groupe/branche.
Modèle d'étude interventionnelle
Comment les traitements sont administrés et testés dans le cadre d'une étude.
Parallèle
Une étude parallèle compare deux groupes ou plus en même temps, chaque groupe recevant un traitement différent. Les chercheurs comparent ensuite les résultats afin de déterminer quel traitement est le plus efficace.
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Expérimental:
AG-120 + Azacitidine
Participants received AG-120 500 mg orally, once daily (QD) in combination with azacitidine 75 milligrams per square meter per day (mg/m\^2/day) subcutaneously (SC) or intravenously (IV), on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation.
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Traitement:
AG-120
Tablets administered orally
Traitement:
Azacitidine
Administered SC or IV
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Comparaison avec le placebo:
Placebo + Azacitidine
Participants received AG-120 matching placebo orally, QD in combination with azacitidine 75 mg/m\^2/day SC or IV, on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation .
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Traitement:
Placebo
Tablets administered orally
Traitement:
Azacitidine
Administered SC or IV
Mots clés
Fournis par Servier
Acute Myeloid Leukemia
Leukemia
Azacitidine
AG-120
ivosidenib
Autres termes
Leukemia, Myeloid, Acute
Leukemia