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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03173248




Registration number
NCT03173248
Ethics application status
Date submitted
30/05/2017
Date registered
1/06/2017

Titles & IDs
Public title
Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Participants With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation
Scientific title
A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of AG-120 in Combination With Azacitidine in Subjects = 18 Years of Age With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation
Secondary ID [1] 0 0
AG120-C-009
Universal Trial Number (UTN)
Trial acronym
AGILE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Newly Diagnosed Acute Myeloid Leukemia (AML) 0 0
Untreated AML 0 0
AML Arising From Myelodysplastic Syndrome (MDS) 0 0
Leukemia, Myeloid, Acute 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AG-120
Treatment: Drugs - Placebo
Treatment: Drugs - Azacitidine

Experimental: AG-120 + Azacitidine - Participants received AG-120 500 mg orally, once daily (QD) in combination with azacitidine 75 milligrams per square meter per day (mg/m\^2/day) subcutaneously (SC) or intravenously (IV), on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation.

Placebo comparator: Placebo + Azacitidine - Participants received AG-120 matching placebo orally, QD in combination with azacitidine 75 mg/m\^2/day SC or IV, on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation .


Treatment: Drugs: AG-120
Tablets administered orally

Treatment: Drugs: Placebo
Tablets administered orally

Treatment: Drugs: Azacitidine
Administered SC or IV

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-Free Survival (EFS)
Timepoint [1] 0 0
Up to Week 24
Secondary outcome [1] 0 0
Complete Remission Rate (CR Rate)
Timepoint [1] 0 0
Up to approximately 52 months
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 52 months
Secondary outcome [3] 0 0
CR + Complete Remission With Partial Hematologic (CRh) Rate
Timepoint [3] 0 0
Up to approximately 52 months
Secondary outcome [4] 0 0
Objective Response Rate (ORR)
Timepoint [4] 0 0
Up to approximately 52 months
Secondary outcome [5] 0 0
CR + CRi (Including CRp) Rate
Timepoint [5] 0 0
Up to approximately 52 months
Secondary outcome [6] 0 0
Duration of CR (DOCR)
Timepoint [6] 0 0
Up to approximately 52 months
Secondary outcome [7] 0 0
Duration of CRh (DOCRh)
Timepoint [7] 0 0
Up to approximately 52 months
Secondary outcome [8] 0 0
Duration of Response (DOR)
Timepoint [8] 0 0
Up to approximately 52 months
Secondary outcome [9] 0 0
Duration of CRi (DOCRi)
Timepoint [9] 0 0
Up to approximately 52 months
Secondary outcome [10] 0 0
Time to CR (TTCR)
Timepoint [10] 0 0
Up to approximately 52 months
Secondary outcome [11] 0 0
Time to CRh (TTCRh)
Timepoint [11] 0 0
Up to approximately 52 months
Secondary outcome [12] 0 0
Time to Response (TTR)
Timepoint [12] 0 0
Up to approximately 52 months
Secondary outcome [13] 0 0
Time to CRi (TTCRi)
Timepoint [13] 0 0
Up to approximately 52 months
Secondary outcome [14] 0 0
Percentage of Participants With Abnormalities in Vital Sign Measurements
Timepoint [14] 0 0
Up to approximately 52 months
Secondary outcome [15] 0 0
Percentage of Participants With Abnormalities in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Timepoint [15] 0 0
Up to approximately 52 months
Secondary outcome [16] 0 0
Percentage of Participants With Abnormalities in 12-lead Electrocardiograms (ECGs)
Timepoint [16] 0 0
Up to approximately 52 months
Secondary outcome [17] 0 0
Percentage of Participants With Abnormalities in Echocardiogram (ECHO) or Multi-Gated Acquisition (MUGA) for Left Ventricular Ejection Fraction (LVEF)
Timepoint [17] 0 0
Up to approximately 52 months
Secondary outcome [18] 0 0
Percentage of Participants With Abnormalities in Clinical Laboratory Tests
Timepoint [18] 0 0
Up to approximately 52 months
Secondary outcome [19] 0 0
Percentage of Participants With Adverse Events (AEs)
Timepoint [19] 0 0
Up to approximately 52 months
Secondary outcome [20] 0 0
Percentage of Participants With AEs of Special Interest (AESIs)
Timepoint [20] 0 0
Up to approximately 52 months
Secondary outcome [21] 0 0
Percentage of Participants With Serious Adverse Events (SAEs)
Timepoint [21] 0 0
Up to approximately 52 months
Secondary outcome [22] 0 0
Percentage of Participants With Adverse Events Leading to Discontinuation or Death
Timepoint [22] 0 0
Up to approximately 52 months
Secondary outcome [23] 0 0
Percentage of Participants Using Concomitant Medications
Timepoint [23] 0 0
Up to approximately 52 months
Secondary outcome [24] 0 0
Units of Platelets and Red Blood Cells (RBC) Infused
Timepoint [24] 0 0
Up to approximately 52 months
Secondary outcome [25] 0 0
Rate of Infection
Timepoint [25] 0 0
Up to approximately 52 months
Secondary outcome [26] 0 0
Number of Days Spent Hospitalized
Timepoint [26] 0 0
Up to approximately 52 months
Secondary outcome [27] 0 0
Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) QLC-C30 Questionnaire
Timepoint [27] 0 0
Up to approximately 52 months
Secondary outcome [28] 0 0
Change From Baseline in the EORTC EQ-5D-5L Questionnaire
Timepoint [28] 0 0
Up to approximately 52 months
Secondary outcome [29] 0 0
Percentage of Participants With CR With IDH1 Mutation Clearance (MC)
Timepoint [29] 0 0
Up to approximately 52 months
Secondary outcome [30] 0 0
Percentage of Participants With Drug Exposure, Dose Modifications and Dose Intensities
Timepoint [30] 0 0
Up to approximately 52 months
Secondary outcome [31] 0 0
Circulating Plasma Concentration of AG-120
Timepoint [31] 0 0
Up to approximately 52 months
Secondary outcome [32] 0 0
Circulating Plasma Concentration of 2-HG
Timepoint [32] 0 0
Up to approximately 52 months

Eligibility
Key inclusion criteria
1. Be = 18 years of age and meet at least 1 of the following criteria defining ineligibility for intensive induction chemotherapy (IC): = 75 years old, Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 2, severe cardiac disorder (e.g., congestive heart failure requiring treatment, left ventricular ejection fraction (LVEF), =50%, or chronic stable angina), severe pulmonary disorder (e.g., diffusing capacity of the lungs for carbon monoxide =65% or forced expiratory volume in 1 second =65%), creatinine clearance <45 mL/minute, bilirubin >1.5 times the upper limit of normal (ULN) and/or have any other comorbidity that the Investigator judges to be incompatible with intensive IC and must be reviewed and approved by the Medical Monitor before study enrollment.
2. Have previously untreated AML, defined according to World Health Organization (WHO) criteria, with = 20% leukemic blasts in the bone marrow. Participants with extramedullary disease alone (i.e., no detectable bone marrow and no detectable peripheral blood AML) are not eligible for the study.
3. Have an isocitrate dehydrogenase 1 (IDH1) mutation.
4. Have an ECOG PS score of 0 to 2.
5. Have adequate hepatic function.
6. Have adequate renal function.
7. Have agreed to undergo serial blood and bone marrow sampling.
8. Be able to understand and willing to sign an informed consent form (ICF).
9. Be willing to complete Quality of Life assessments during the study
10. If female with reproductive potential, must have a negative serum pregnancy test prior to the start of study therapy. Females of reproductive potential, as well as fertile men and their female partners of reproductive potential, must agree to use 2 effective forms of contraception.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Are candidates for and willing to receive intensive induction chemotherapy (IC) for their AML.
2. Have received any prior treatment for AML with the exception of hydroxyurea.
3. Have received a hypomethylating agent for myelodysplastic syndrome (MDS).
4. Participants who had previously received an experimental agent for MDS may not be randomized until a washout period has elapsed since the last dose of that agent.
5. Have received prior treatment with an IDH1 inhibitor.
6. Have a known hypersensitivity to any of the components of AG-120, matched placebo, or azacitidine.
7. Are female and pregnant or breastfeeding.
8. Have an active, uncontrolled, systemic fungal, bacterial, or viral infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.
9. Have a prior history of cancer other than MDS or myeloproliferative disorder, unless the participant has been free of the disease for = 1 year prior to the start of study treatment.
10. Have had significant active cardiac disease within 6 months prior to the start of the study treatment.
11. Have any condition that increases the risk of abnormal ECG or cardiac arrhythmia.
12. Have a condition that limits the ingestion or absorption of drugs administered by mouth.
13. Have uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or diastolic BP > 100 mmHg).
14. Have clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia.
15. Have immediate, life-threatening, severe complications of leukemia, such as uncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminated intravascular coagulation.
16. Have any other medical or psychological condition deemed by the Investigator to be likely to interfere with the participant's ability to give informed consent or participate in the study.
17. Are taking medications that are known to prolong the QT interval unless they can be transferred to other medications within =5 half-lives prior to dosing, or unless the medications can be properly monitored during the study. (If equivalent medication is not available, heart rate corrected QT interval [QTc] will be closely monitored.)
18. Have a known medical history of progressive multifocal leukoencephalopathy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford park
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
5042 - Bedford park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Kentucky
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
Austria
State/province [3] 0 0
Salzburg
Country [4] 0 0
Austria
State/province [4] 0 0
Wien
Country [5] 0 0
Brazil
State/province [5] 0 0
Sao Paulo
Country [6] 0 0
Brazil
State/province [6] 0 0
Rio De Janeiro
Country [7] 0 0
Canada
State/province [7] 0 0
Manitoba
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
China
State/province [9] 0 0
Henan
Country [10] 0 0
China
State/province [10] 0 0
Sichuan
Country [11] 0 0
China
State/province [11] 0 0
Beijing
Country [12] 0 0
China
State/province [12] 0 0
Guangzhou
Country [13] 0 0
China
State/province [13] 0 0
Hangzhou
Country [14] 0 0
China
State/province [14] 0 0
Tianjin
Country [15] 0 0
Czechia
State/province [15] 0 0
Ostrava
Country [16] 0 0
France
State/province [16] 0 0
Gironde
Country [17] 0 0
France
State/province [17] 0 0
Indre-et-Loire
Country [18] 0 0
France
State/province [18] 0 0
Loire-Atlantique
Country [19] 0 0
France
State/province [19] 0 0
Rhone
Country [20] 0 0
France
State/province [20] 0 0
Sarthe
Country [21] 0 0
France
State/province [21] 0 0
Brest
Country [22] 0 0
France
State/province [22] 0 0
Caen
Country [23] 0 0
France
State/province [23] 0 0
Grenoble
Country [24] 0 0
France
State/province [24] 0 0
Le Chesnay
Country [25] 0 0
France
State/province [25] 0 0
Paris
Country [26] 0 0
France
State/province [26] 0 0
Poitiers
Country [27] 0 0
France
State/province [27] 0 0
Strasbourg
Country [28] 0 0
France
State/province [28] 0 0
Toulouse
Country [29] 0 0
France
State/province [29] 0 0
Villejuif
Country [30] 0 0
Germany
State/province [30] 0 0
Nordrhein-Westfalen
Country [31] 0 0
Germany
State/province [31] 0 0
Sachsen
Country [32] 0 0
Germany
State/province [32] 0 0
Berlin
Country [33] 0 0
Germany
State/province [33] 0 0
Hannover
Country [34] 0 0
Germany
State/province [34] 0 0
Leipzig
Country [35] 0 0
Germany
State/province [35] 0 0
Munchen
Country [36] 0 0
Germany
State/province [36] 0 0
Ulm
Country [37] 0 0
Israel
State/province [37] 0 0
Petah Tikva
Country [38] 0 0
Israel
State/province [38] 0 0
Rehovot
Country [39] 0 0
Italy
State/province [39] 0 0
Lombardia
Country [40] 0 0
Italy
State/province [40] 0 0
Meldola
Country [41] 0 0
Italy
State/province [41] 0 0
Milano
Country [42] 0 0
Italy
State/province [42] 0 0
Pavia
Country [43] 0 0
Italy
State/province [43] 0 0
Rimini
Country [44] 0 0
Italy
State/province [44] 0 0
Torino
Country [45] 0 0
Japan
State/province [45] 0 0
Ehime
Country [46] 0 0
Japan
State/province [46] 0 0
Fukui
Country [47] 0 0
Japan
State/province [47] 0 0
Himeji
Country [48] 0 0
Japan
State/province [48] 0 0
Kobe
Country [49] 0 0
Korea, Republic of
State/province [49] 0 0
Gyeonggido
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Busan
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Seoul
Country [52] 0 0
Mexico
State/province [52] 0 0
Culiacan
Country [53] 0 0
Mexico
State/province [53] 0 0
Mexico
Country [54] 0 0
Netherlands
State/province [54] 0 0
Noord-Holland
Country [55] 0 0
Netherlands
State/province [55] 0 0
Nijmegen
Country [56] 0 0
Poland
State/province [56] 0 0
Dolnoslaskie
Country [57] 0 0
Poland
State/province [57] 0 0
Mazowieckie
Country [58] 0 0
Poland
State/province [58] 0 0
Gdansk
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Kaluga
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Moscow
Country [61] 0 0
Spain
State/province [61] 0 0
A Coruna
Country [62] 0 0
Spain
State/province [62] 0 0
Baleares
Country [63] 0 0
Spain
State/province [63] 0 0
Barcelona
Country [64] 0 0
Spain
State/province [64] 0 0
Las Palmas
Country [65] 0 0
Spain
State/province [65] 0 0
Madrid
Country [66] 0 0
Spain
State/province [66] 0 0
Sevilla
Country [67] 0 0
Spain
State/province [67] 0 0
Valencia
Country [68] 0 0
Spain
State/province [68] 0 0
Zaragoza
Country [69] 0 0
Taiwan
State/province [69] 0 0
Changhua City
Country [70] 0 0
Taiwan
State/province [70] 0 0
Kaohsiung
Country [71] 0 0
Taiwan
State/province [71] 0 0
Taichung City
Country [72] 0 0
Taiwan
State/province [72] 0 0
Tainan City
Country [73] 0 0
Taiwan
State/province [73] 0 0
Taipei
Country [74] 0 0
United Kingdom
State/province [74] 0 0
West Midlands

Funding & Sponsors
Primary sponsor type
Other
Name
Institut de Recherches Internationales Servier
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
After Marketing Authorisation in EEA or US if the study is used for the approval.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://clinicaltrials.servier.com/


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.