None listed
Conditions
Brief summary
The purpose of this study is to investigate the efficacy and safety of Ivosidenib and Enasidenib in patients with acute myeloid Leukaemia or myelodysplastic syndrome (MDS). Who is it for? You may be eligible for this study if you are an adult who has been diagnosed with AML or MDS with either an IDH1 or IDH2 mutation, with no previous chemotherapy treatment. Study details Participants in this study will receive the following treatments: 1.Up to two cycles of Induction: Cytarabine for 6 days and Daunorubicin once a day for 3 days through an infusion in the vein. You will be randomly assigned either a placebo (no treatment) or Enasidenib or Ivosidenaib orally with a tablet once a day for the whole cycle. 2.Up to three cycles of consolidation: Cytarabine twice a day through an infusion in the vein over 3 days. You may then receive either a placebo (no treatment) or Enasidenib or Ivosidenaib orally with a tablet once a day until the end of consolidation. 3.Maintenance treatment will be either a placebo (no treatment), Enasidenib or Ivosidenaib for up to two years. All participants will undertake blood tests, bone marrow biopsies, scans and questionnaires.
Interventions
Patients will be randomised depending on whether they have an isocitrate dehydrogenases 1 (IDH1) or isocitrate dehydrogenases 2 (IDH2) mutation.
IDH1 Cohort will recieve
Induction cycle 1 (Cycle equals 28 days)
Cytarabine 200 mg/m2, continuous 24-hour Intravenous infusion, Days 1 to 7.
Daunorubicin 60 mg/m2 Intravenous, (1hr infusion) Days 1,2,3
Placebo or Ivosidenib 500 mg, Orally (tablet) once a day for the whole cycle.
Induction Cycle 2 (Cycle equals 28 days)
Cytarabine 2000 mg/m2, 3 hr Intr
Patients will be randomised depending on whether they have an isocitrate dehydrogenases 1 (IDH1) or isocitrate dehydrogenases 2 (IDH2) mutation. IDH1 Cohort will recieve Induction cycle 1 (Cycle equals 28 days) Cytarabine 200 mg/m2, continuous 24-hour Intravenous infusion, Days 1 to 7. Daunorubicin 60 mg/m2 Intravenous, (1hr infusion) Days 1,2,3 Placebo or Ivosidenib 500 mg, Orally (tablet) once a day for the whole cycle. Induction Cycle 2 (Cycle equals 28 days) Cytarabine 2000 mg/m2, 3 hr Intravenous infusions 1000 mg/m2 every 12 hrs, Days 1 to 6 Daunorubicin (Only for patients less than 60 years of age) 60 mg/m2 Intravenous, 1hr infusion,Days 1 to 3. Patients over 60 do not receive Daunorubicin in cycle 2. Placebo or Ivosidenib 500 mg orally Days 1 to start of consolidation treatment Consolidation treatment Cytarabine 3000 mg/m2 (age less than or equal to 60yrs), 3hr Intravenous infudion, 1500 mg every 12 hrs × 6 doses, Days1-3 2000 mg/m2 (age greater than or equal to 61yrs), 3-hour Intravenous infusion, 1000 mg every 12 hrs × 6 doses, Days1-3 Placebo or Ivosidenib 500 mg, orally once a day until start of maintenance Maintenance Placebo or Ivosidenib 500 mg, orally Days 1 to 730 (aprox 2 years) IDH2 Cohort will recieve Induction Cycle 1 Cytarabine 200 mg/m2, continuous 24-hour intravenous infusion, Days 1 to 7 Daunorubicin 60 mg/m2 Intravenous, (1hr infusion) Days 1,2,3 Placebo or Enasidenib 100 mg, Orally, once a day for the whole cycle Induction cycle 2 Cytarabine 2000 mg/m2, 3 hr Intravenous infusions 1000 mg/m2 every 12 hrs, Days1 to 6. Daunorubicin (Only for patients less than or equal to 60 years of age) 60 mg/m2 Intravenous, (1hr infusion) Days 1 to 3 Placebo or Enasidenib 100 mg Orally, once a day until start of consolidation treatment. Consolidation treatment Cytarabine 3000 mg/m2 (age less than or equal to 60yrs), 3hr Intravenous infusion, 1500 mg every 12 hrs × 6 doses, Days1-3 2000 mg/m2 (age greater than or equal to 61yrs), 3-hour Intravenous infusion, 1000 mg every 12 hrs × 6 doses, Days1-3 Placebo or Enasidenib 100 mg, Orally, once a day until start of maintenance Maintenance Placebo or Enasidenib, 100 mg, Orally, Day 1 to 730 (aprox 2 years)
Sponsors
HOVON (the Haemato Oncology Foundation for Adults in the Netherlands)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age greater than or equal to 18 years Newly diagnosed AML or MDS-EB2 defined according to WHO criteria, with a documented IDH1 or IDH2 gene mutation (as determined by the clinical trial assay) Considered to be eligible for intensive chemotherapy. ECOG/WHO performance status less than or equal to 2 Adequate hepatic function . Adequate renal function Able to understand and willing to sign an informed consent form (ICF). Female patients of reproductive potential must undergo a pregnancy test prior to starting study drug and this test must have a negative result. Females of reproductive potential as well as fertile men and their partners who are females of reproductive potential must agree to abstain from sexual intercourse or to use a highly effective form of contraception from the time of giving informed consent, during the study, Subject agrees not to participate in another interventional study while on treatment
Exclusion criteria
Prior chemotherapy for AML or MDS-EB2. Dual IDH1 and IDH2 mutations.. Acute promyelocytic leukemia (APL) Blast crisis after chronic myeloid leukemia (CML). Taking medications with narrow therapeutic windows with potential interaction with investigational medication Breast feeding at the start of study treatment. Active infection, including hepatitis B or C or HIV infection that is uncontrolled at randomization. Patients with a currently active second malignancy. Significant active cardiac disease within 6 months prior to the start of study treatment. Dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs. Any other medical condition deemed by the Investigator to be likely to interfere with a patient’s ability to give informed consent or participate in the study.
Outcome results
None listed