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A Study to Assess the Safety and Efficacy of Two Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) Harboring IDH Mutations Who Are Not Candidates to Receive Intensive Induction Chemotherapy

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ClinicalTrials.gov Identifier: NCT02677922
Recruitment Status : Active, not recruiting
First Posted : February 9, 2016
Last Update Posted : August 19, 2022
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:

The purpose of this study are

  1. to determine the recommended combination dose of AG-120 and AG-221 separately when administered with azacitidine and,
  2. to investigate the safety, tolerability, and efficacy of the combinations of AG-120 with azacitidine and AG-221 with azacitidine versus with azacitidine alone in participants with acute myeloid leukemia (AML) with the isocitrate dehydrogenase (IDH) enzyme isoforms 1 or 2 mutations, respectively.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Drug: AG-120 Drug: Azacitidine Drug: AG-221 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 131 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Open-Label, Randomized Study of 2 Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine: Oral AG-120 Plus Subcutaneous Azacitidine and Oral AG-221 Plus SC Azacitidine in Subjects With Newly Diagnosed Acute Myeloid Leukemia Harboring an IDH1 or an IDH2 Mutation, Respectively, Who Are Not Candidates to Receive Intensive Induction Chemotherapy
Actual Study Start Date : June 3, 2016
Actual Primary Completion Date : August 2, 2018
Estimated Study Completion Date : January 4, 2023


Arm Intervention/treatment
Experimental: AG-120 + Azacitidine Drug: AG-120
Specified dose on specified days

Drug: Azacitidine
Specified dose on specified days

Experimental: AG-221 + Azacitidine Drug: Azacitidine
Specified dose on specified days

Drug: AG-221
Specified dose on specified days

Experimental: Azacitidine Drug: Azacitidine
Specified dose on specified days




Primary Outcome Measures :
  1. Dose limiting toxicities (DLTs) [ Time Frame: Up to approximately 8 months ]
  2. Incidence of adverse events (AEs) [ Time Frame: Up to approximately 8 years ]
  3. Pharmacokinetics - Maximum observed plasma concentration (Cmax) [ Time Frame: Up to approximately 8 months ]
  4. Pharmacokinetics - Time to maximum concentration (Tmax) [ Time Frame: Up to approximately 8 months ]
  5. Pharmacokinetics - Area under the plasma concentration time curve (AUC) [ Time Frame: Up to approximately 8 months ]
  6. Overall response rate (ORR) as assessed by the investigator [ Time Frame: Up to approximately 30 months ]

Secondary Outcome Measures :
  1. ORR as assessed by the investigator [ Time Frame: Up to approximately 13 months ]
  2. Sponsor derived morphologic complete remission (CR) [ Time Frame: Up to approximately 13 months ]
  3. Sponsor derived morphologic complete remission with partial hematologic recovery (CRh) [ Time Frame: Up to approximately 13 months ]
  4. Event-Free Survival [ Time Frame: Up to approximately 30 months ]
  5. Incidence of AEs [ Time Frame: Up to approximately 8 years ]
  6. Complete remission rate [ Time Frame: Up to approximately 30 months ]
  7. Hematologic improvement rate [ Time Frame: Up to approximately 30 months ]
  8. Duration of Response according to modified International Working Group (IWG) acute myeloid leukemia (AML) response criteria [ Time Frame: Up to approximately 30 months ]
  9. Time to response according to modified IWG AML response criteria [ Time Frame: Up to approximately 30 months ]
  10. Time to sponsored assessed CR [ Time Frame: Up to approximately 30 months ]
  11. Time to sponsored assessed CRh [ Time Frame: Up to approximately 30 months ]
  12. Duration of sponsor assessed CR [ Time Frame: Up to approximately 30 months ]
  13. Duration of sponsor assessed CRh [ Time Frame: Up to approximately 30 months ]
  14. Overall Survival [ Time Frame: Up to approximately 30 months ]
  15. One-year survival [ Time Frame: Up to approximately 12 months ]
  16. Pharmacokinetics - Cmax [ Time Frame: Up to approximately 30 months ]
  17. Pharmacokinetics - Tmax [ Time Frame: Up to approximately 30 months ]
  18. Pharmacokinetics - AUC [ Time Frame: Up to approximately 30 months ]
  19. Change from baseline in European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30) [ Time Frame: Up to approximately 30 months ]
  20. Change from baseline in Health Questionnaire (EQ-5D-5L) [ Time Frame: Up to approximately 30 months ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Newly diagnosed, primary (ie, de novo) or secondary (progression of Myelodysplastic syndrome [MDS] or myeloproliferative neoplasms [MPN], or therapy-related) acute myeloid leukemia (AML) according to the WHO classification with ≥ 20% leukemic blasts in the bone marrow
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Agree to serial bone marrow aspirate/biopsies

Exclusion Criteria:

  • Suspected or proven to have acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype
  • AML secondary to chronic myelogenous leukemia (CML)
  • Received a targeted agent against an isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2) mutation
  • Has or is suspected of having central nervous system (CNS) leukemia. Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is suspected during screening

Other protocol defined inclusion/exclusion criteria apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02677922


Locations
Show Show 73 study locations
Sponsors and Collaborators
Celgene
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02677922    
Other Study ID Numbers: AG-221-AML-005
2015-003951-23 ( EudraCT Number )
First Posted: February 9, 2016    Key Record Dates
Last Update Posted: August 19, 2022
Last Verified: August 2022
Keywords provided by Celgene:
Acute Myeloid Leukemia
Leukemia
Azacitidine
AG-120
AG-221
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors