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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05907057
Other study ID # DIM-95031-006
Secondary ID 2022-501709-11
Status Recruiting
Phase Phase 3
First received
Last updated
Start date June 14, 2023
Est. completion date December 15, 2026

Study information

Verified date November 2023
Source Servier
Contact Servier Affaires Médicales
Phone +33 1 55 72 60 00
Email scientificinformation@servier.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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 information / eligibility

Status Recruiting
Enrollment 245
Est. completion date December 15, 2026
Est. primary completion date January 1, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - 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 Exclusion Criteria: - 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


Intervention

Drug:
Ivosidenib 500mg Oral Tablet
Provided as tablets, taken orally as two 250mg tablets once daily.
Azacitidine
Administered subcutaneously (SC) or intravenously (IV) at a dose of 75mg/m2/day for 7 days, either consecutively on Days 1-7 or discontinuously for Days 1-5 and 8-9 of each cycle. The 7 days of administration will occur at the beginning of every 4 week-long cycle.

Locations

Country Name City State
Austria AKH - Medizinische Universität Wien Vienna
Austria Klinikum Wels-Grieskirchen GmbH Wels
France CHU Angers - Hôpital Hôtel Dieu Angers Liore
France CHU CAEN - Hôpital de la Côte de Nacre Caen Calvados
France Institut Paoli Calmettes Marseille Bouches-du-Rhône
France CHU Rennes - Hopital Pontchaillou Rennes Ille Et Vilaine
France CHU de Toulouse pt Toulouse Haute Garonne
Italy Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili) Brescia
Italy IRCCS Ospedale Policlinico San Martino Genova
Italy IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST Meldola Forli-Cesena
Italy Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia Perugia
Netherlands Meander Medisch Centrum Amersfoort
Netherlands Amsterdam UMC Amsterdam
Netherlands Rijnstate Arnhem
Netherlands Universitair Medisch Centrum Groningen Groningen

Sponsors (1)

Lead Sponsor Collaborator
Servier Affaires Médicales

Countries where clinical trial is conducted

Austria,  France,  Italy,  Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Adverse Events (AEs) Adverse events (AEs) will be graded according to the CTCAE v5.0 up to week 116
Primary Number of Serious Adverse Events (SAEs) Adverse events (AEs) will be graded according to the CTCAE v5.0 up to week 116
Primary Differentiation Syndrome of Grade 2 or higher up to week 116
Primary Number of Adverse Events (AEs) leading to ivosidenib + azacitidine discontinuation up to week 112
Primary Number of Adverse Events (AEs) leading to ivosidenib + azacitidine interruption up to week 112
Primary Number of Adverse Events (AEs) leading to ivosidenib + azacitidine dose reduction up to week 112
Primary Number of Adverse Events (AEs) leading to death up to week 116
Primary Number of clinical laboratory anomalies assessed as Adverse Events (AEs) up to week 116
Primary Number of patients requiring transfusion (platelet and RBC) and the average number of units transfused up to week 116
Primary Rate of infections Infection rates will be summarized by classification and will include a count and proportion. up to week 116
Primary QT Prolongation event assessed as Grade 3 or higher up to week 116
Secondary Event-free survival (EFS) up to week 116
Secondary Proportion of patients who achieve a complete remission (CR) up to week 116
Secondary Proportion of patients who achieve complete remission plus complete remission with partial hematologic recovery rate (CR + CRh) up to week 116
Secondary Proportion of patients who achieve complete remission plus complete remission with incomplete hematologic recovery rate (CR + CRi) up to week 116
Secondary Duration of response (DOR) up to week 116
Secondary Time to response (TTR) up to week 116
Secondary Overall survival (OS) until study closure
Secondary Quality of life (QoL), as measured by Hematologic Malignancy-Patient-Reported Outcome (HM-PRO) For patients with a baseline assessment and at least 1 post-baseline assessment that generates a score up to week 116
Secondary Quality of life (QoL), as measured by Family Reported Outcome Measure (FROM-16), for caregivers and/or family For patients with a baseline assessment and at least 1 post-baseline assessment that generates a score up to week 116
Secondary Health economic measures, as assessed by the 5-level EuroQol 5-Dimensions (EQ-5D-5L) For patients with a baseline assessment and at least 1 post-baseline assessment that generate a score up to week 116
Secondary Average proportion of days at home 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 up to week 116
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