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


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Verified May 2017 by Agios Pharmaceuticals, Inc.

Sponsor:

Information provided by (Responsible Party):

Agios Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT03173248

First received: May 30, 2017

Last updated: May 30, 2017

Last verified: May 2017

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.

Newly Diagnosed Acute Myeloid Leukemia (AML)
Untreated AML
AML Arising From Myelodysplastic Syndrome (MDS)
Leukemia, Myeloid, Acute
Drug: AG-120 (ivosidenib) with Azacitidine
Drug: Placebo with Azacitidine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator
Primary Purpose: Treatment
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

Primary Outcome Measures:

  • Overall Survival [ Time Frame: 12 Months, on average ]

Secondary Outcome Measures:

  • 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 ]

Estimated Enrollment: 392
Anticipated Study Start Date: June 2017
Estimated Study Completion Date: June 2022
Estimated Primary Completion Date: April 2022 (Final data collection date for primary outcome measure)
Experimental: AG-120 (ivosidenib) with Azacitidine 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

Placebo Comparator: Placebo with Azacitidine 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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03173248

Contact: Medical Affairs Agios Pharmaceuticals, Inc. (844) 633-2332 medinfo@agios.com

Agios Pharmaceuticals, Inc.

Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03173248     History of Changes
Other Study ID Numbers: AG120-C-009
Study First Received: May 30, 2017
Last Updated: May 30, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Agios Pharmaceuticals, Inc.:

Acute Myeloid Leukemia
Leukemia
Azacitidine
AG-120
ivosidenib

Additional relevant MeSH terms:

Leukemia, Myeloid
Leukemia
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on June 01, 2017