Status and phase
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Study type
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Identifiers
About
The primary objectives of Phase 1 Dose Escalation/Part 1 Expansion are:
The primary objective of Phase 2 is:
• To assess the efficacy of enasidenib as treatment for participants with relapsed or refractory (R/R) acute myelogenous leukemia (AML) with an IDH2 mutation.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Phase 1/ Dose escalation:
Diagnosis of acute myelogenous leukemia (AML) according to World Health Organization (WHO) criteria;
Diagnosis of Myelodysplastic syndrome (MDS) according to WHO classification with refractory anemia with excess blasts (RAEB-1 or RAEB-2), or considered high-risk by the Revised International Prognostic Scoring System (IPSS-R), that is recurrent or refractory, or the subject is intolerant to established therapy known to provide clinical benefit for their condition (i.e., subjects must not be candidates for regimens known to provide clinical benefit), according to the treating physician and with approval of the Medical Monitor.
Phase 1/Part 1 Expansion:
Arm 1: Relapsed or refractory AML and age greater than or equal to 60 years or any subject with AML regardless of age who has relapsed following a bone marrow transplant (BMT).
Arm 2: Relapsed or refractory AML and age <60 years, excluding subjects with AML who have relapsed following a BMT.
Arm 3: Untreated AML and age greater than or equal to 60 years that decline standard of care chemotherapy.
Arm 4: Isocitrate dehydrogenase protein, 2 (IDH2)-mutated advanced hematologic malignancies not eligible for Arms 1 to 3.
Phase 2:
Diagnosis of AML according to World Health Organization (WHO) criteria and disease relapsed or refractory as defined by:
Subjects must have documented IDH2 gene-mutated disease:
Subjects must be amenable to serial bone marrow sampling, peripheral blood sampling and urine sampling during the study.
The diagnosis and evaluation of AML or MDS will be made by bone marrow aspiration and/or biopsy. If an aspirate is unobtainable (i.e., a "dry tap"), the diagnosis may be made from the core biopsy.
Screening bone marrow aspirate and peripheral blood samples are required of all subjects. A bone marrow biopsy must be collected if adequate aspirate is not attainable unless:
Subjects must be able to understand and willing to sign an informed consent. A legally authorized representative may consent on behalf of a subject who is otherwise unable to provide informed consent, if acceptable to and approved by the site and/or sites Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 to 2.
Platelet count ≥ 20,000/μL (transfusions to achieve this level are allowed). Subjects with a baseline platelet count of < 20,000/μL due to underlying malignancy are eligible with Medical Monitor approval.
Subjects must have adequate hepatic function as evidenced by:
Subjects must have adequate renal function as evidenced by:
• Serum creatinine ≤ 2.0 × ULN OR
• Creatinine clearance greater than 40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation: (140 - Age) x (weight in kg) x (0.85 if female)/72 x serum creatinine
Subjects must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer. (Subjects with residual Grade 1 toxicity, for example Grade 1 peripheral neuropathy or residual alopecia, are allowed with approval of the Medical Monitor)
Female subjects of child-bearing potential must agree to undergo medically supervised pregnancy test prior to starting study drug. The first pregnancy test will be performed at screening (within 7 days prior to first study drug administration), and on the day of the first study drug administration and confirmed negative prior to dosing and Day 1 before dosing all subsequent cycles.
Female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy. Subjects with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy or tubal occlusion or who have not been naturally postmenopausal (i.e., who have not menstruated at all) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Females of reproductive potential as well as fertile men and their partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study and for 120 days (females and males) following the last dose of AG-221. A highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization.
Able to adhere to the study visit schedule (ie, clinic visits at the study sites are mandatory, unless noted otherwise for particular study visits) and other protocol requirements.
Exclusion criteria
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345 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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