Treatment of 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 2 (IDH2) mutation MedDRA version: 20.0 Level: LLT Classification code 10060558 Term: Acute myeloid leukemia recurrent System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT C
Conditions
Interventions
Product Name: enasidenib
Product Code: AG-221
Pharmaceutical Form: Tablet
INN or Proposed INN: enasidenib
Current Sponsor code: AG-221
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject is = 60 years of age at the time of signing the ICF 2. Subject has primary (ie, de novo) or secondary (progression of MDS or myeloproliferative neoplasms ([MPN], or therapy-related) AML according to WHO classification 3. Subject has received 2nd- or 3rd-line/regimen of AML therapy. (See app G for the definition of prior AML line/regimen); note that, for subjects having AML secondary to prior higher risk [Intermediate-2 or High risk according to the International Prognostic Scoring System] MDS treated with a hypomethylating agent [eg, azacitidine or decitabine], the hypomethylating therapy can be counted as a line/regimen if there is disease progression to AML during or shortly [eg, within 60 days] after the hypomethylating therapy.) 4. Subject has the following disease status: a. Refractory to or relapsed after 2nd- or 3rd-line/regimen of intensive therapy for AML (eg, the “7 + 3” regimen): at least 5% leukemic blasts in bone marrow; (the minimum number of treatment cycles of the intensive therapy is per the investigator's discretion); or b. Refractory to or relapsed after second- or 3rd-line low-intensity AML therapy (eg, LDAC, azacitidine or decitabine): at least 5% leukemic blasts in bone marrow after at least 2 treatment cycles 5. Subject is eligible for and willing to receive the pre-selected CCR treatment option, according to the investigator's assessment (Note: Subjects with degenerative and toxic encephalopathies, especially after the use of methotrexate or treatment with ionizing radiation, should not receive cytarabine.) 6. Subject has ECOG performance status of 0, 1 or 2 7. Subject has IDH2 gene mutations tested centrally (using the “investigational use only” PCR assay, Abbott RealTime IDH2) in samples of bone marrow aspirate and peripheral blood, and confirmed positive in bone marrow aspirate and/or peripheral blood. (Note: in the event that the central laboratory result is delayed and precludes acute clinical management of a subject who has confirmed IDH2 gene mutation by local evaluation, the subject may be eligible for randomization with approval by the Medical Monitor.) 8. Subject has adequate organ function defined as: - Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) = 3 x upper limit of normal (ULN), unless considered due to leukemic organ involvement, following review by the Medical Monitor; and - Serum total bilirubin = 1.5 x ULN, unless considered due to Gilbert’s syndrome (eg, a gene mutation in UGT1A1) or leukemic organ involvement, following review by the Medical Monitor; and - Creatinine clearance > 30 mL/min based on the Modification of Diet in Renal Disease (MDRD) glomerular filtration rate (GFR): GFR (mL/min/1.73 m2) = 175 × (serum creatinine)-1.154 × (Age)0.203 × (0.742 if female) × (1.212 if African Ame
Exclusion criteria
Exclusion criteria: 1. Subject is suspected or proven to have acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype 2. Subject has AML secondary to chronic myelogenous leukemia 3. Subject has received a targeted agent against an IDH2 mutation 4. Subject has received systemic anticancer therapy or radiotherapy < 14 days prior to the start of study treatment. Note that hydroxyurea is allowed prior to the start of study treatment for the control of leukocytosis (however, hydroxyurea should not be given within 72 hours prior to and after administration of azacitidine) 5. Subject has received non-cytotoxic or investigational agents < 14 days or 5 half-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, or on immunosuppressive therapy post HSCT at the 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 steroids for ongoing skin GVHD is permitted. 7. Subject has persistent, clinically significant non-hematologic toxicities from prior therapies 8. Subject 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the primary efficacy, measured as overall survival (OS), of AG-221 compared with conventional care regimens (CCRs) in subjects 60 years or older with AML refractory to or relapsed after second- or third-line AML therapy and positive for an IDH2 mutation; Secondary Objective: -To determine the supporting efficacy of AG-221 compared with CCRs -To determine the safety and tolerability of AG-221 compared with CCRs -To determine the effect of AG-221 compared with CCRs on Health-related Quality-of-Life ;Primary end point(s): Overall survival;Timepoint(s) of evaluation of this end point: 49 months in total (42 months for enrollment and screening and 7 months treatment and/ or post treatment follow up) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Overall response rate 2.Event-free survival 3.Duration of response 4.Time to response 5.Treatment mortality at 30 and 60 days 6.One-year survival 7.Overall remission rate 8.Complete remission rate 9.Hematologic improvement rate 10.Rate of HSCT 11.Time to treatment failure 12.Safety and tolerability 13.HRQoL ; Timepoint(s) of evaluation of this end point: 1.up to approximately 49 months 2.up to approximately 49 months 3.up to approximately 49 months 4.up to approximately 49 months 5.At 30 and 60 days after treatment start 6.up to approximately 49 months 7.up to approximately 49 months 8.up to approximately 49 months 9.up to approximately 49 months 10.up to approximately 49 months 11.up to approximately 49 months 12.up to approximately 78 months 13.up to approximately 49 months | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, Denmark, France, Germany, Italy, Japan, Korea, Republic of, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed