Clinical trial NCT05907057: 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.
Official title: A Single Arm, Open-label Phase 3b Study to Describe the Safety and Tolerability of Ivosidenib in Combination With Azacitidine in Adult Patients Newly Diagnosed With IDH1m Acute Myeloid Leukemia (AML) Ineligible for Intensive Induction Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Myeloid Leukemia (AML)
Keywords: IDH1 Mutation AML
Lead sponsor: Servier
Sponsor class: INDUSTRY
First posted: 2023-06-18
Enrollment: 245
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Adverse Events (AEs)
timeFrame: up to week 116
measure: Number of Serious Adverse Events (SAEs)
timeFrame: up to week 116
measure: Differentiation Syndrome of Grade 2 or higher
timeFrame: up to week 116
measure: Number of Adverse Events (AEs) leading to ivosidenib + azacitidine discontinuation
timeFrame: up to week 112
measure: Number of Adverse Events (AEs) leading to ivosidenib + azacitidine interruption
timeFrame: up to week 112
measure: Number of Adverse Events (AEs) leading to ivosidenib + azacitidine dose reduction
timeFrame: up to week 112
measure: Number of Adverse Events (AEs) leading to death
timeFrame: up to week 116
measure: Number of clinical laboratory anomalies assessed as Adverse Events (AEs)
timeFrame: up to week 116
measure: Number of patients requiring transfusion (platelet and RBC) and the average number of units transfused
timeFrame: up to week 116
measure: Rate of infections
timeFrame: up to week 116
measure: QT Prolongation event assessed as Grade 3 or higher
timeFrame: up to week 116
Secondary outcomes:
measure: Event-free survival (EFS)
timeFrame: up to week 116
measure: Proportion of patients who achieve a complete remission (CR)
timeFrame: up to week 116
measure: Proportion of patients who achieve complete remission plus complete remission with partial hematologic recovery rate (CR + CRh)
timeFrame: up to week 116
measure: Proportion of patients who achieve complete remission plus complete remission with incomplete hematologic recovery rate (CR + CRi)
timeFrame: up to week 116
measure: Duration of response (DOR)
timeFrame: up to week 116
measure: Time to response (TTR)
timeFrame: up to week 116
measure: Overall survival (OS)
timeFrame: until study closure
measure: Quality of life (QoL), as measured by Hematologic Malignancy-Patient-Reported Outcome (HM-PRO)
timeFrame: up to week 116
measure: Quality of life (QoL), as measured by Family Reported Outcome Measure (FROM-16), for caregivers and/or family
timeFrame: up to week 116
measure: Health economic measures, as assessed by the 5-level EuroQol 5-Dimensions (EQ-5D-5L)
timeFrame: up to week 116
measure: Average proportion of days at home
timeFrame: up to week 116
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: AKH - Medizinische Universität Wien
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Marseille
country: France
facility: Institut Paoli Calmettes
state: Bouches-du-Rhône
city: Caen
country: France
facility: CHU CAEN - Hôpital de la Côte de Nacre
state: Calvados
city: Toulouse
country: France
facility: CHU de Toulouse pt
state: Haute Garonne
city: Rennes
country: France
facility: CHU Rennes - Hopital Pontchaillou
state: Ille et Vilaine
city: Angers
country: France
facility: CHU Angers - Hôpital Hôtel Dieu
state: Liore
city: Meldola
country: Italy
facility: IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST
state: Forli-Cesena
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
Study officials:
References: