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.

Acute Myeloid Leukemia (AML) Clinical Trial

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

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
• 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
• 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)

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

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