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.
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Participants who are eligible and enroll in the study will be on treatment for a maximum of 112 weeks (28 cycles), during which they 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. This study will build on previous studies to gather additional safety data and also focus on the drugs impact on the participant and their families quality of life. 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Open-Label Ivosidenib in combination with 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. |
Drug: Ivosidenib Oral Tablet
Provided as tablets, taken orally once daily.
Drug: Azacitidine
Administered subcutaneously (SC) or intravenously (IV) 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.
|
Outcome Measures
Primary Outcome Measures
- Number of Adverse Events (AEs) [up to week 116]
Adverse events (AEs) will be graded according to the CTCAE v5.0
- Number of Serious Adverse Events (SAEs) [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]
- Number of Adverse Events (AEs) leading to ivosidenib + azacitidine discontinuation [up to week 112]
- Number of Adverse Events (AEs) leading to ivosidenib + azacitidine interruption [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]
- 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]
Secondary Outcome Measures
- Event-free survival (EFS) [up to week 116]
- Proportion of patients who achieve a complete remission (CR) [up to week 116]
- Proportion of patients who achieve complete remission plus complete remission with partial hematologic recovery rate (CR + CRh) [up to week 116]
- Proportion of patients who achieve complete remission plus complete remission with incomplete hematologic recovery rate (CR + CRi) [up to week 116]
- Duration of response (DOR) [up to week 116]
- Time to response (TTR) [up to week 116]
- Overall survival (OS) [until study closure]
- 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
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has untreated Acute Myeloid Leukemia (AML)
-
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
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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
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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
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Is a woman who is pregnant or breastfeeding
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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
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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
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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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | AKH - Medizinische Universität Wien | Vienna | Austria | ||
| 2 | Klinikum Wels-Grieskirchen GmbH | Wels | Austria | ||
| 3 | Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili) | Brescia | Italy | 25123 | |
| 4 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 |
Sponsors and Collaborators
- Servier
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DIM-95031-006
- 2022-501709-11