NCT02577406

An Efficacy and Safety Study of AG-221 (CC-90007) Versus Conventional Care Regimens in Older Subjects With Late Stage Acute Myeloid Leukemia Harboring an Isocitrate Dehydrogenase 2 Mutation

A Phase 3, Multicenter, Open-label, Randomized Study Comparing the Efficacy and Safety of AG-221 (CC-90007) Versus Conventional Care Regimens in Older Subjects With Late Stage Acute Myeloid Leukemia Harboring an Isocitrate Dehydrogenase 2 Mutation

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 319 (actual)
• Sponsor: Celgene · Industry
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

This is an international, multicenter, open-label, randomized, Phase 3 study comparing the efficacy and safety of AG-221 versus conventional care regimens (CCRs) in subjects 60 years or older with acute myeloid leukemia (AML) refractory to or relapsed after second- or third-line AML therapy and positive for an isocitrate dehydrogenase (IDH2) mutation.

Detailed description

Acute myeloid leukaemia (AML) is a form of cancer that is common in older patients. Mutations in the isocitrate dehydrogenase enzyme 2 (IDH2) have been found in approximately 15% of patients with AML. The outcome of first line chemotherapy treatment is poor and many patients fail to attain complete remission (CR, ie refractory) or will eventually relapse. There is no single standard of care for relapsed or refractory AML. Since the prognosis is very poor there is a great need for new therapies. Inhibition of the mutant IDH2 enzyme may represent a promising targeted therapy for AML. AG-221 is a small molecule inhibitor of the IDH2 enzyme, designed to preferentially target the mutant IDH2 variants. Data from the ongoing first-in-human study has shown AG-221 to be generally well tolerated and demonstrated CR in patients with IDH2 mutation positive relapsed or refractory AML. The study purpose is to test the safety and efficacy of AG-221 compared with conventional care regimens (CCR), which include best supportive care (BSC) only, azacitidine plus BSC, low-dose cytarabine plus BSC or intermediate-dose cytarabine plus BSC, in patients with late stage AML refractory to or relapsed after second or third line therapy and positive for the IDH2 mutation. Patients will be randomly assigned to receive open-label tablets of AG-221 or one of the CCR on continuous 28-day treatment cycles. The trial duration is expected to be 78 months which includes 42 months enrollment, approximately 7 months treatment and a follow-up period. Study procedures include: vital signs, physical exams, ECGs, ECHO, urine/blood samples, bone marrow aspirates and/or biopsies and peripheral blood to test for IDH2 and assess treatment response. Bone marrow, blood, cheek swab samples will be used for genetic tests. This study is being sponsored by Celgene Corporation. Approximately 316 participants will take part in the study.

Conditions

• Leukemia, Myeloid
• Isocitrate Dehydrogenase

Interventions

Type	Name	Description
DRUG	AG-221	Continuous 28-day cycles of AG 221 100 mg orally (PO) once a day (QD) for 28 days
OTHER	BSC	Best supportive care includes, hydroxyurea for leukocytosis and/or differentiation-like syndrome, anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support
DRUG	Azacitidine	continuous 28-day cycles of azacitidine 75 mg/m2/day SC for 7 days, plus BSC
DRUG	Low-dose cytarabine (LDAC)	continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC
DRUG	Intermediate-dose cytarabine (IDAC)	28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after IDAC therapy concludes per standard institutional practice

Timeline

• Start date: 2015-12-30
• Primary completion: 2020-03-17
• Completion: 2024-03-25
• First posted: 2015-10-16
• Last updated: 2025-05-18
• Results posted: 2022-09-10

Locations

93 sites across 18 countries: United States, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Italy, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom