TriangleNCT03173248 · CITED IN SOURCE DOCUMENTS
Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Participants With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-06-29
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 participants with previously untreated IDH1m AML who are considered appropriate candidates for non-intensive therapy. The primary endpoint is event-free survival (EFS). The key secondary efficacy endpoints are overall survival (OS), rate of complete remission (CR), rate of CR and complete remission with partial hematologic recovery (CRh), and overall response rate (ORR). Participants 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 200 participants will take part in the study.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Event-Free Survival (EFS)
Complete Remission Rate (CR Rate)
Overall Survival (OS)
CR + Complete Remission With Partial Hematologic (CRh) Rate
Objective Response Rate (ORR)
CR + CRi (Including CRp) Rate
Duration of CR (DOCR)
Duration of CRh (DOCRh)
Duration of Response (DOR)
Duration of CRi (DOCRi)
Time to CR (TTCR)
Time to CRh (TTCRh)
Time to Response (TTR)
Time to CRi (TTCRi)
Percentage of Participants With Abnormalities in Vital Sign Measurements
Percentage of Participants With Abnormalities in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Percentage of Participants With Abnormalities in 12-lead Electrocardiograms (ECGs)
Percentage of Participants With Abnormalities in Echocardiogram (ECHO) or Multi-Gated Acquisition (MUGA) for Left Ventricular Ejection Fraction (LVEF)
Percentage of Participants With Abnormalities in Clinical Laboratory Tests
Percentage of Participants With Adverse Events (AEs)
Percentage of Participants With AEs of Special Interest (AESIs)
Percentage of Participants With Serious Adverse Events (SAEs)
Percentage of Participants With Adverse Events Leading to Discontinuation or Death
Percentage of Participants Using Concomitant Medications
Units of Platelets and Red Blood Cells (RBC) Infused
Rate of Infection
Number of Days Spent Hospitalized
Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) QLC-C30 Questionnaire
Change From Baseline in the EORTC EQ-5D-5L Questionnaire
Percentage of Participants With CR With IDH1 Mutation Clearance (MC)
Percentage of Participants With Drug Exposure, Dose Modifications and Dose Intensities
Circulating Plasma Concentration of AG-120
Circulating Plasma Concentration of 2-HG
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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. 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 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.
- intervention Names
- Drug: AG-120
- Drug: Azacitidine
- label
- AG-120 + Azacitidine
- type
- EXPERIMENTAL
- description
- 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 .
- intervention Names
- Drug: Placebo
- Drug: Azacitidine
- label
- Placebo + Azacitidine
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- AG-120 + Azacitidine
- description
- Tablets administered orally
- name
- AG-120
- other Names
- Ivosidenib
- type
- DRUG
- arm Group Labels
- Placebo + Azacitidine
- description
- Tablets administered orally
- name
- Placebo
- type
- DRUG
- arm Group Labels
- AG-120 + Azacitidine
- Placebo + Azacitidine
- description
- Administered SC or IV
- name
- Azacitidine
- other Names
- Vidaza®
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- TRIPLE
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 146
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- EFS was defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure was defined as failure to achieve complete remission (CR) by Week 24. CR: Bone marrow blasts \<5% and no Auer rods; absence of extramedullary disease; Absolute neutrophil count (ANC) ≥1.0 × 10\^9 per litre (10\^9/L) (1000 per microlitre \[1000/μL\]); platelet count ≥100 × 10\^9/L (100,000/μL); independence of red blood cell transfusions. Participants who had an EFS event (relapse or death) after, 2 or more missing disease assessments were censored at the last adequate disease assessment documenting no relapse before the missing assessments. The reported data represents the Kaplan-Meier median value.
- measure
- Event-Free Survival (EFS)
- time Frame
- Up to Week 24
- secondary Outcomes
- description
- CR rate is defined as the proportion of participants who achieve a CR. A Cochran-Mantel-Haenszel (CMH) test will be used to compare CR rate between the 2 treatment arms.
- measure
- Complete Remission Rate (CR Rate)
- time Frame
- Up to approximately 52 months
- description
- OS is defined as the time from date of randomization to the date of death due to any cause. Kaplan-Meier (KM) curves and KM estimates of OS will be presented for each treatment arm.
- measure
- Overall Survival (OS)
- time Frame
- Up to approximately 52 months
- description
- CR + CRh rate is defined as the proportion of participants who achieve a CR or CRh. CRh is defined as a CR with partial recovery of peripheral blood counts (less than 5% bone marrow blasts, absolute neutrophil count (ANC) greater than 0.5 × 10\^9/liter (L) 500/microliter (μL)\], and platelets greater than 50 × 10\^9/L \[50,000/μL\]). A CMH test will be used to compare the CR + CRh rate between the 2 treatment arms.
- measure
- CR + Complete Remission With Partial Hematologic (CRh) Rate
- time Frame
- Up to approximately 52 months
- description
- ORR is defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery \[CRp\]), partial remission (PR), and morphologic leukemia-free state (MLFS). The best response is calculated using the following hierarchy: CR, followed by CRi (including CRp), followed by PR and MLFS. A summary of best response by treatment arm will be produced. A CMH test will be used to compare ORR between the 2 treatment arms.
- measure
- Objective Response Rate (ORR)
- time Frame
- Up to approximately 52 months
- description
- The CR + CRi (including CRp) rate is defined as the proportion of participants who achieve a CR or CRi (including CRp). A CMH test will be used to compare the CR + CRi (including CRp) rate between the 2 treatment arms.
- measure
- CR + CRi (Including CRp) Rate
- time Frame
- Up to approximately 52 months
- description
- DOCR will be calculated as the date of the first occurrence of CR to the date of first documented disease relapse, or death. DOCR is only defined for participants who achieve a CR.
- measure
- Duration of CR (DOCR)
- time Frame
- Up to approximately 52 months
- description
- DOCRh will be calculated as the date of the first occurrence of CR or CRh to the date of first documented disease relapse or death. DOCRh is only defined for participants who achieve a CR or CRh.
- measure
- Duration of CRh (DOCRh)
- time Frame
- Up to approximately 52 months
- description
- DOR will be calculated as the date of the first response to the date of first documented disease relapse, disease progression, or death. DOR is only defined for participants who achieve a CR, CRi (including CRp), PR, and/or MLFS.
- measure
- Duration of Response (DOR)
- time Frame
- Up to approximately 52 months
- description
- DOCRi will be calculated as the date of the first occurrence of CR or CRi (including CRp) to the date of the first documented relapse or death. DOCRi is only defined for participants who achieve a CR or CRi (including CRp).
- measure
- Duration of CRi (DOCRi)
- time Frame
- Up to approximately 52 months
- description
- TTCR will be assessed from the date of randomization to the date of first occurrence of CR. TTCR is only defined for participants who achieve a CR.
- measure
- Time to CR (TTCR)
- time Frame
- Up to approximately 52 months
- description
- TTCRh will be assessed from the date of randomization to the date of first occurrence of CR or CRh. TTCRh is only defined for participants who achieve a CR or CRh.
- measure
- Time to CRh (TTCRh)
- time Frame
- Up to approximately 52 months
- description
- TTR will be assessed from the date of randomization to the date of the first response. TTR is only defined for participants who achieve a CR, CRi (including CRp), PR, and/or MLFS.
- measure
- Time to Response (TTR)
- time Frame
- Up to approximately 52 months
Full study description
- 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 participants with previously untreated IDH1m AML who are considered appropriate candidates for non-intensive therapy. The primary endpoint is event-free survival (EFS). The key secondary efficacy endpoints are overall survival (OS), rate of complete remission (CR), rate of CR and complete remission with partial hematologic recovery (CRh), and overall response rate (ORR). Participants 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 200 participants will take part in the study.
Source references
- avail Ipds
- type
- Individual Participant Data Set
- type
- Study Protocol
- type
- Statistical Analysis Plan
- type
- Informed Consent Form
- type
- Clinical Study Report
- type
- Study-level clinical trial data
- references
- citation
- Montesinos P, Recher C, Vives S, Zarzycka E, Wang J, Bertani G, Heuser M, Calado RT, Schuh AC, Yeh SP, Daigle SR, Hui J, Pandya SS, Gianolio DA, de Botton S, Dohner H. Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia. N Engl J Med. 2022 Apr 21;386(16):1519-1531. doi: 10.1056/NEJMoa2117344.
- pmid
- 35443108
- type
- BACKGROUND
- citation
- Montesinos P, Marchione DM, Recher C, Heuser M, Vives S, Zarzycka E, Wang J, Riva M, Calado RT, Schuh AC, Yeh SP, Tron AE, Hui J, Gianolio DA, Choe S, Patel P, De Botton S, DiNardo CD, Dohner H. Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed IDH1-mutated AML. Blood Adv. 2025 Oct 28;9(20):5177-5189. doi: 10.1182/bloodadvances.2025016399.
- pmid
- 40706052
- type
- DERIVED
- citation
- Woods A, Norsworthy KJ, Wang X, Vallejo J, Chiu Yuen Chow E, Li RJ, Sun J, Charlab R, Jiang X, Pazdur R, Theoret MR, de Claro RA. FDA Approval Summary: Ivosidenib in Combination with Azacitidine for Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia with an IDH1 Mutation. Clin Cancer Res. 2024 Apr 1;30(7):1226-1231. doi: 10.1158/1078-0432.CCR-23-2234.
- pmid
- 38010220
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-aa924f7e0f2bd8a43503
- requested nct id
- NCT03173248
- primary nct id
- NCT03173248
- source kind
- fda_spl_label
- source record id
- 190606ed-cb7f-411b-8548-cc2f98e57819
- source file sha256
- 0dba7a040bbbf460aa9f482c5b67c9f28f75fc9df775ee1e7b345b758f780e07
- payload sha256
- e2f2b60f17b8ed3b9db7825c9ea6d0dc16b413e1722808146fba42af4cab8c73
- payload
- application numbers
- NDA211192
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-aa924f7e0f2bd8a43503
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT03173248
- occurrences
- context exact
- with Azacitidine The efficacy of TIBSOVO was evaluated in a randomized (1:1), multicenter, double-blind, placebo-controlled clinical trial (Study AG120-C-009, NCT03173248) of 146 adult patients with newly-diagnosed AML with an IDH1 mutation who were 75 years or older, or had comorbidities that precluded the use of intensive indu
- end
- 250
- exact text
- NCT03173248
- start
- 239
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00000.json
- source file sha256
- 0dba7a040bbbf460aa9f482c5b67c9f28f75fc9df775ee1e7b345b758f780e07
- source json pointer
- /results/84/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 190606ed-cb7f-411b-8548-cc2f98e57819
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 84ba6c27686a2a9c8e820cf0af0e664bd96467139019277d93f7fcd35db383df
- spl effective time
- 20251222
- spl set id
- 65d254c0-67ad-42c4-b972-ad463b755b2d
Preserved source evidence · Not medical advice