Back to resultsAn 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.
Primary Purpose
Acute Myeloid Leukemia (AML)
Status
Recruiting
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Ivosidenib 500mg Oral Tablet
Azacitidine
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring IDH1 Mutation AML
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)
Sites / Locations
- Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum DüsseldorfRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Open-Label Ivosidenib in combination with Azacitidine
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of Adverse Events (AEs)
Adverse events (AEs) will be graded according to the CTCAE v5.0
Number of Serious Adverse Events (SAEs)
Adverse events (AEs) will be graded according to the CTCAE v5.0
Differentiation Syndrome of Grade 2 or higher
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine discontinuation
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine interruption
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine dose reduction
Number of Adverse Events (AEs) leading to death
Number of clinical laboratory anomalies assessed as Adverse Events (AEs)
Number of patients requiring transfusion (platelet and RBC) and the average number of units transfused
Rate of infections
Infection rates will be summarized by classification and will include a count and proportion.
QT Prolongation event assessed as Grade 3 or higher
Secondary Outcome Measures
Event-free survival (EFS)
Proportion of patients who achieve a complete remission (CR)
Proportion of patients who achieve complete remission plus complete remission with partial hematologic recovery rate (CR + CRh)
Proportion of patients who achieve complete remission plus complete remission with incomplete hematologic recovery rate (CR + CRi)
Duration of response (DOR)
Time to response (TTR)
Overall survival (OS)
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
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
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
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
Full Information
NCT ID
NCT05907057
First Posted
June 8, 2023
Last Updated
August 29, 2023
Sponsor
Servier Affaires Médicales
1. Study Identification
Unique Protocol Identification Number
NCT05907057
Brief Title
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
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 14, 2023 (Actual)
Primary Completion Date
January 1, 2026 (Anticipated)
Study Completion Date
December 15, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Servier Affaires Médicales
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML)
Keywords
IDH1 Mutation AML
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
245 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Open-Label Ivosidenib in combination with Azacitidine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ivosidenib 500mg Oral Tablet
Intervention Description
Provided as tablets, taken orally as two 250mg tablets once daily.
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Adverse Events (AEs)
Description
Adverse events (AEs) will be graded according to the CTCAE v5.0
Time Frame
up to week 116
Title
Number of Serious Adverse Events (SAEs)
Description
Adverse events (AEs) will be graded according to the CTCAE v5.0
Time Frame
up to week 116
Title
Differentiation Syndrome of Grade 2 or higher
Time Frame
up to week 116
Title
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine discontinuation
Time Frame
up to week 112
Title
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine interruption
Time Frame
up to week 112
Title
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine dose reduction
Time Frame
up to week 112
Title
Number of Adverse Events (AEs) leading to death
Time Frame
up to week 116
Title
Number of clinical laboratory anomalies assessed as Adverse Events (AEs)
Time Frame
up to week 116
Title
Number of patients requiring transfusion (platelet and RBC) and the average number of units transfused
Time Frame
up to week 116
Title
Rate of infections
Description
Infection rates will be summarized by classification and will include a count and proportion.
Time Frame
up to week 116
Title
QT Prolongation event assessed as Grade 3 or higher
Time Frame
up to week 116
Secondary Outcome Measure Information:
Title
Event-free survival (EFS)
Time Frame
up to week 116
Title
Proportion of patients who achieve a complete remission (CR)
Time Frame
up to week 116
Title
Proportion of patients who achieve complete remission plus complete remission with partial hematologic recovery rate (CR + CRh)
Time Frame
up to week 116
Title
Proportion of patients who achieve complete remission plus complete remission with incomplete hematologic recovery rate (CR + CRi)
Time Frame
up to week 116
Title
Duration of response (DOR)
Time Frame
up to week 116
Title
Time to response (TTR)
Time Frame
up to week 116
Title
Overall survival (OS)
Time Frame
until study closure
Title
Quality of life (QoL), as measured by Hematologic Malignancy-Patient-Reported Outcome (HM-PRO)
Description
For patients with a baseline assessment and at least 1 post-baseline assessment that generates a score
Time Frame
up to week 116
Title
Quality of life (QoL), as measured by Family Reported Outcome Measure (FROM-16), for caregivers and/or family
Description
For patients with a baseline assessment and at least 1 post-baseline assessment that generates a score
Time Frame
up to week 116
Title
Health economic measures, as assessed by the 5-level EuroQol 5-Dimensions (EQ-5D-5L)
Description
For patients with a baseline assessment and at least 1 post-baseline assessment that generate a score
Time Frame
up to week 116
Title
Average proportion of days at home
Description
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
Time Frame
up to week 116
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Servier Affaires Médicales
Phone
+33 1 55 72 60 00
Email
scientificinformation@servier.com
Facility Information:
Facility Name
Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.
Access can be requested for all interventional clinical studies:
used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.
In addition, access can be requested for all interventional clinical studies in patients:
sponsored by Servier
with a first patient enrolled as of 1 January 2004 onwards
for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
IPD Sharing Time Frame
After Marketing Authorization in EEA or US if the study is used for the approval.
IPD Sharing Access Criteria
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
IPD Sharing URL
http://clinicaltrials.servier.com/
Learn more about this trial
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.
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