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

Celgene

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Leukemia, Myeloid, Acute

Treatments: Drug: Azacitidine; Drug: AG-120; Drug: AG-221

Study type: Interventional

Funder types: Industry

Identifiers

NCT02677922

AG-221-AML-005

2015-003951-23 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 130 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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130 participants in 3 patient groups

AG-120 + Azacitidine

Experimental group

Treatment:

Drug: Azacitidine

Drug: AG-120

AG-221 + Azacitidine

Experimental group

Treatment:

Drug: AG-221

Drug: Azacitidine

Azacitidine

Experimental group

Treatment:

Drug: Azacitidine