Description:
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.
Title
- Brief Title: Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Patients With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation
- Official 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
Clinical Trial IDs
- ORG STUDY ID:
AG120-C-009
- NCT ID:
NCT03173248
Conditions
- Newly Diagnosed Acute Myeloid Leukemia (AML)
- Untreated AML
- AML Arising From Myelodysplastic Syndrome (MDS)
- Leukemia, Myeloid, Acute
Interventions
Drug | Synonyms | Arms |
---|
AG-120 (ivosidenib) with Azacitidine | | AG-120 (ivosidenib) with Azacitidine |
Placebo with Azacitidine | | Placebo with Azacitidine |
Purpose
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 Arms
Name | Type | Description | Interventions |
---|
AG-120 (ivosidenib) with Azacitidine | Experimental | | - AG-120 (ivosidenib) with Azacitidine
|
Placebo with Azacitidine | Placebo Comparator | | |
Eligibility Criteria
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.
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall Survival |
Time Frame: | 12 Months, on average |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Event Free Survival (EFS) |
Time Frame: | 8 Months, on average |
Safety Issue: | |
Description: | |
Measure: | Complete Remission Rate (CR Rate) |
Time Frame: | 8 Months, on average |
Safety Issue: | |
Description: | |
Measure: | CR + CRh Rate |
Time Frame: | 8 Months, on average |
Safety Issue: | |
Description: | |
Measure: | Objective Response Rate (ORR) |
Time Frame: | 8 Months, on average |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Agios Pharmaceuticals, Inc. |
Trial Keywords
- Acute Myeloid Leukemia
- Leukemia
- Azacitidine
- AG-120
- ivosidenib
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