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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03173248
Ethics application status
Date submitted
30/05/2017
Date registered
30/05/2017
Date last updated
6/02/2019

Titles & IDs
Public title
Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Patients 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 (ivosidenib) with Azacitidine
Treatment: Drugs - Placebo with Azacitidine

Experimental: AG-120 (ivosidenib) with Azacitidine -

Placebo Comparator: Placebo with Azacitidine -


Treatment: Drugs: AG-120 (ivosidenib) with Azacitidine
Continuous 28-day cycles of AG-120 (ivosidenib) 500 mg orally (PO) once daily (QD) in combination with azacitidine 75 mg/m2/day SC or IV for the first week of each cycle

Treatment: Drugs: Placebo with Azacitidine
Continuous 28-day cycles of Placebo orally (PO) once daily (QD) in combination with azacitidine 75 mg/m2/day SC or IV for the first week of each cycle

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

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
12 Months, on average
Secondary outcome [1] 0 0
Event Free Survival (EFS)
Timepoint [1] 0 0
8 Months, on average
Secondary outcome [2] 0 0
Complete Remission Rate (CR Rate)
Timepoint [2] 0 0
8 Months, on average
Secondary outcome [3] 0 0
CR + CRh Rate
Timepoint [3] 0 0
8 Months, on average
Secondary outcome [4] 0 0
Objective Response Rate (ORR)
Timepoint [4] 0 0
8 Months, on average

Eligibility
Key inclusion criteria
1. Be = 18 years of age.

2. Have previously untreated AML, defined according to WHO criteria, with = 20% leukemic
blasts in the bone marrow. Subjects with extramedullary disease alone (ie, 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 Performance Status 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
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Are candidates for and willing to receive intensive 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. Subjects 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 subject 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
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 subject's ability to give informed consent or participate
in the study.

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
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,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment hospital [2] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
- Perth
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
- Bedford Park
Recruitment outside Australia
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United States of America
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California
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Georgia
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Illinois
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Indiana
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Kentucky
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Louisiana
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Massachusetts
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South Carolina
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Texas
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Austria
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Salzburg
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Wien
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Goiás
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Paraná
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Rio Grande Do Sul
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Quebec
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Czechia
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Ostrava
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Czechia
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Gironde
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Cáceres
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Madrid, Communidad Delaware
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Madrid
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Coruña
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Spain
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Las Palmas De Gran Canaria
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Spain
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Murcia
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Spain
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Sevilla
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Spain
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Valencia
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Spain
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Zaragoza
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Taiwan
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Changhua City
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Taiwan
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Kaohsiung
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Taiwan
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Taichung City
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Taiwan
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Tainan City
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United Kingdom
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Kent
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United Kingdom
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Oxfordshire
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Birmingham
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Boston
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Dundee
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Agios Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Study AG120-C-009 is a global, Phase 3, multicenter, double-blind, randomized,
placebo-controlled clinical trial to evaluate the efficacy and safety of AG-120 (ivosidenib)
+ azacitidine vs placebo + azacitidine in adult subjects with previously untreated IDH1m AML
who are considered appropriate candidates for non-intensive therapy. The primary endpoint is
Overall Survival (OS). The key secondary efficacy endpoints are Event free Survival (EFS),
rate of complete remission (CR), Rate of CR and complete remission with partial hematologic
recovery (CRh), and overall response rate (ORR). Subjects eligible for study treatment based
on Screening assessments will be randomized 1:1 to receive oral AG-120 or matched placebo,
both administered in combination with subcutaneous (SC) or intravenous (IV) azacitidine. An
estimated 392 subjects will participate in the study.
Trial website
https://clinicaltrials.gov/show/NCT03173248
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
Medical Affairs Agios Pharmaceuticals, Inc.
Address 0 0
Country 0 0
Phone 0 0
1.833.228.8474
Fax 0 0
Email 0 0
medinfo@agios.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable