An Open-label Phase 3b Study of Ivosidenib in Combination With Azacitidine in Adult Patients Newly Diagnosed With IDH1m Acute Myeloid Leukemia (AML) Ineligible for Intensive Induction Chemotherapy.
- Conditions
- Acute Myeloid Leukemia (AML)
- Interventions
- Registration Number
- NCT05907057
- Lead Sponsor
- Servier Affaires Médicales
- Brief Summary
The purpose of this study is to learn more about the safety and efficacy of ivosidenib taken with azacitidine to treat adult patients with acute myeloid leukemia (AML) who are presenting a gene mutation called IDH1 (isocitrate dehydrogenase1 mutation-positive \[IDH1m\]) and cannot receive treatment with intensive chemotherapy (IC).
- Detailed Description
Participants who are eligible and enroll in the study will attend a study visit on the first day of each 28-day cycle. Study visits will consist of a physical exam, blood work, electrocardiogram (ECG) and other assessments. After treatment discontinuation participants will be contacted every 12 weeks through the end of the study (currently planned for 2026) to assess survival. The study drug, Ivosidenib, will be taken once daily throughout the duration of participation in the study, and Azacitidine will only be administered for 7 days at the beginning of each 28 day cycle. If at any point ivosidenib is made available as a medical prescription at the patient's site, the patient will switch to commercial product and will continue to be followed according to the protocol.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 245
- Has untreated Acute Myeloid Leukemia (AML)
- Have a documented IDH1 R132 gene-mutated disease
- Have at least one of the following making yourself ineligible for intensive chemotherapy (IC): 75 years or older, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2, or any comorbidity that the investigator judges to be incompatible with IC including but not limited to severe cardiac or pulmonary disorder, creatinine clearance less than 45 mL/minute, or bilirubin greater than 1.5 times the upper limit of normal
- Has adequate hepatic (liver) and renal (kidney) function
- Female participants of reproductive potential must have a negative blood pregnancy test and must use effective contraception during treatment and for at least 6 months following treatment
- Fertile male participants with female partners of reproductive potential must use effective contraception during treatment and for at least 3 months following treatment
- Has received any prior treatment for AML, with the exception of hydroxyurea or leukapheresis for white blood cell count control
- Has received prior treatment with an IDH1 inhibitor
- Is a woman who is pregnant or breastfeeding
- Has an active, uncontrolled, systemic fungal, bacterial, or viral infection (including human immunodeficiency virus [HIV], active hepatitis B (HBV), or hepatitis C virus [HCV]) without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment
- Has had significant active cardiac disease within 6 months prior to the start of study treatment, including Class III or IV congestive heart failure, myocardial infarction (heart attack), unstable angina (chest pain), and/or stroke
- Has dysphagia (difficulty swallowing), short-gut syndrome, gastroparesis (stomach paralysis), or any other condition that limits the ingestion or gastrointestinal absorption of orally administered drugs
- Has uncontrolled hypertension (high blood pressure)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Open-Label Ivosidenib in combination with Azacitidine Ivosidenib 500mg Oral Tablet All participants will receive both Ivosidenib and Azacitidine for a maximum of 28 cycles. Each cycle will be 4 weeks or 28 days long. Ivosidenib will be taken continuously throughout each cycle and Azacitidine will be taken only for 7 days at the beginning of each cycle. Open-Label Ivosidenib in combination with Azacitidine Azacitidine All participants will receive both Ivosidenib and Azacitidine for a maximum of 28 cycles. Each cycle will be 4 weeks or 28 days long. Ivosidenib will be taken continuously throughout each cycle and Azacitidine will be taken only for 7 days at the beginning of each cycle.
- Primary Outcome Measures
Name Time Method Number of Adverse Events (AEs) up to week 116 Adverse events (AEs) will be graded according to the CTCAE v5.0
Differentiation Syndrome of Grade 2 or higher up to week 116 Rate of infections up to week 116 Infection rates will be summarized by classification and will include a count and proportion.
QT Prolongation event assessed as Grade 3 or higher up to week 116 Number of Adverse Events (AEs) leading to ivosidenib + azacitidine discontinuation up to week 112 Number of Adverse Events (AEs) leading to ivosidenib + azacitidine dose reduction up to week 112 Number of Adverse Events (AEs) leading to death up to week 116 Number of clinical laboratory anomalies assessed as Adverse Events (AEs) up to week 116 Number of patients requiring transfusion (platelet and RBC) and the average number of units transfused up to week 116 Number of Serious Adverse Events (SAEs) up to week 116 Adverse events (AEs) will be graded according to the CTCAE v5.0
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine interruption up to week 112
- Secondary Outcome Measures
Name Time Method Proportion of patients who achieve complete remission plus complete remission with partial hematologic recovery rate (CR + CRh) up to week 116 Duration of response (DOR) up to week 116 Health economic measures, as assessed by the 5-level EuroQol 5-Dimensions (EQ-5D-5L) up to week 116 For patients with a baseline assessment and at least 1 post-baseline assessment that generate a score
Overall survival (OS) until study closure Average proportion of days at home up to week 116 Defined by subtracting the number of care days (days hospitalized or seen in an ED / oncology clinic / infusion center) from the total days of follow-up, divided by total days of follow-up
Proportion of patients who achieve a complete remission (CR) up to week 116 Event-free survival (EFS) up to week 116 Quality of life (QoL), as measured by Hematologic Malignancy-Patient-Reported Outcome (HM-PRO) up to week 116 For patients with a baseline assessment and at least 1 post-baseline assessment that generates a score
Quality of life (QoL), as measured by Family Reported Outcome Measure (FROM-16), for caregivers and/or family up to week 116 For patients with a baseline assessment and at least 1 post-baseline assessment that generates a score
Proportion of patients who achieve complete remission plus complete remission with incomplete hematologic recovery rate (CR + CRi) up to week 116 Time to response (TTR) up to week 116
Trial Locations
- Locations (15)
AKH - Medizinische Universität Wien
🇦🇹Vienna, Austria
Klinikum Wels-Grieskirchen GmbH
🇦🇹Wels, Austria
Institut Paoli Calmettes
🇫🇷Marseille, Bouches-du-Rhône, France
CHU CAEN - Hôpital de la Côte de Nacre
🇫🇷Caen, Calvados, France
CHU de Toulouse pt
🇫🇷Toulouse, Haute Garonne, France
CHU Rennes - Hopital Pontchaillou
🇫🇷Rennes, Ille et Vilaine, France
CHU Angers - Hôpital Hôtel Dieu
🇫🇷Angers, Liore, France
IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST
🇮🇹Meldola, Forli-Cesena, Italy
IRCCS Ospedale Policlinico San Martino
🇮🇹Genova, Italy
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
🇮🇹Brescia, Italy
Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
🇮🇹Perugia, Italy
Meander Medisch Centrum
🇳🇱Amersfoort, Netherlands
Amsterdam UMC
🇳🇱Amsterdam, Netherlands
Rijnstate
🇳🇱Arnhem, Netherlands
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands