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

Last updated: September 29, 2015
Sponsor: Celgene Corporation
Overall Status: Active - Not Recruiting

Phase

3

Condition

Leukemia

Treatment

N/A

Clinical Study ID

NCT02564510
AG-221-AML-004
  • Ages > 60
  • Both

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study:

  1. Subject is ≥ 60 years of age at the time of signing the Informed Consent Form (ICF)

  2. Subject has primary (ie, de novo) or secondary (progression of Myelodysplasticsyndromes (MDS) or myeloproliferative neoplasms ([MPN], or therapy-related) Acutemyeloid leukemia (AML) according to World Health Organization (WHO) classification

  3. Subject has received second- or third-line/regimen of AML therapy

  4. Subject has the following disease status:

  • Refractory to or relapsed after second- or third-line/regimen of intensivetherapy for AML (eg, the "7 + 3" regimen):

  • at least 5% leukemic blasts in bone marrow; or

  • Refractory to or relapsed after second- or third-line low-intensity AML therapy (eg, LDAC, azacitidine or decitabine):

  • at least 5% leukemic blasts in bone marrow after at least 2 treatment cycles

Exclusion

Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment:

  1. Subject is suspected or proven to have acute promyelocytic leukemia based onmorphology, immunophenotype, molecular assay, or karyotype

  2. Subject has Acute myeloid leukemia (AML) secondary to chronic myelogenous leukemia (CML)

  3. Subject has received a targeted agent against an IDH2 mutation

  4. Subject has received systemic anticancer therapy or radiotherapy < 14 days prior tothe start of study treatment. Note that hydroxyurea is allowed prior to the start ofstudy treatment for the control of leukocytosis in subjects with white blood cell (WBC) counts > 30 x 109/L (however, hydroxyurea should not be given within 72 hoursprior to and after administration of azacitidine).

  5. Subject has received non-cytotoxic or investigational agents < 14 days or 5half-lives, whichever is longer, prior to the start of study treatment

  6. Subject has undergone HSCT within 60 days prior to the start of study treatment, oron immunosuppressive therapy post Hematopoietic stem cell transplantation (HSCT) atthe time of screening, or with clinically significant graft-versus-host disease (GVHD). The use of a stable dose of oral steroid post-HSCT and/or topical steroidsfor ongoing skin Graft-versus-host disease (GVHD) is permitted.

Study Design

Total Participants: 280
Study Start date:
October 01, 2015
Estimated Completion Date:
February 29, 2020

Study 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 IDH2 mutations may represent a promising targeted therapy for AML. AG-221 is designed to only block the IDH2 mutations. 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 28 months which includes 24 months enrollment, approximately 4 months treatment and a follow-up period.

Study procedures include: vital signs, physical exams, ECGs, ECHO/ MUGAs, 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 280 participants will take part in the study.