Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Patients With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation (AGILE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03173248
Recruitment Status : Recruiting
First Posted : June 1, 2017
Last Update Posted : October 24, 2019
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE May 30, 2017
First Posted Date  ICMJE June 1, 2017
Last Update Posted Date October 24, 2019
Actual Study Start Date  ICMJE June 26, 2017
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2017)
Overall Survival [ Time Frame: 12 Months, on average ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03173248 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2017)
  • Event Free Survival (EFS) [ Time Frame: 8 Months, on average ]
  • Complete Remission Rate (CR Rate) [ Time Frame: 8 Months, on average ]
  • CR + CRh Rate [ Time Frame: 8 Months, on average ]
  • Objective Response Rate (ORR) [ Time Frame: 8 Months, on average ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Newly Diagnosed Acute Myeloid Leukemia (AML)
  • Untreated AML
  • AML Arising From Myelodysplastic Syndrome (MDS)
  • Leukemia, Myeloid, Acute
Intervention  ICMJE
  • Drug: 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
  • Drug: 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
Study Arms  ICMJE
  • Experimental: AG-120 (ivosidenib) with Azacitidine
    Intervention: Drug: AG-120 (ivosidenib) with Azacitidine
  • Placebo Comparator: Placebo with Azacitidine
    Intervention: Drug: Placebo with Azacitidine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 30, 2017)
392
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Affairs Agios Pharmaceuticals, Inc. 1.833.228.8474 medinfo@agios.com
Listed Location Countries  ICMJE Australia,   Austria,   Brazil,   Canada,   China,   Czechia,   France,   Germany,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Russian Federation,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03173248
Other Study ID Numbers  ICMJE AG120-C-009
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Agios Pharmaceuticals, Inc.
Study Sponsor  ICMJE Agios Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Agios Pharmaceuticals, Inc.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP