Clinical Trials /

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

NCT03173248

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 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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

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

DrugSynonymsArms
AG-120 (ivosidenib) with AzacitidineAG-120 (ivosidenib) with Azacitidine
Placebo with AzacitidinePlacebo 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

NameTypeDescriptionInterventions
AG-120 (ivosidenib) with AzacitidineExperimental
  • AG-120 (ivosidenib) with Azacitidine
Placebo with AzacitidinePlacebo Comparator
  • Placebo with Azacitidine

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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