AML and MDS-EB2 are malignancies of the bone marrow. The standard treatment for these diseases is chemotherapy. Patients participating have a special type of this disease because the leukemia cells (blasts) have developed an error in the genetic material (DNA). This error is called an IDH1 mutation or an IDH2 mutation (a mutation is a change in the DNA), which leads to changes in specific substances in the leukemia cells. This trial will investigate whether the addition of the new drugs Ivosidenib (for patients with IDH1 mutation) or Enasidenib (for patients with IDH2 mutation) to the standard treatment of chemotherapy controle the disease more effectively and for a longer period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
968
250mg tablets
250mg tablets
100mg tablets
100mg tablets
AU-Adelaide-FLINDERS
Adelaide, Australia
AU-Adelaide-RAH
Adelaide, Australia
AU-Brisbane-PAH
Brisbane, Australia
AU-Camperdown-RPA
Camperdown, Australia
AU-Canberra-CANBERRAHOSPITAL
Canberra, Australia
AU-Douglas-TOWNSVILLE
Douglas, Australia
Event-free survival (EFS)
EFS is defined as the time from randomization to failure to achieve CR or CRi after remission induction, death after achieving CR or CRi or relapse after achieving CR or CRi, whichever occurs first. A patient is said to have failed to achieve CR or CRi after induction therapy, if his/her best response during or at completion of the induction treatment is less than CRi. Patients who achieved CR/CRi after remission induction and are not known to have relapsed or died will be censored at the date of last clinical assessment.
Time frame: Approximately up to 60 months following first patient enrollment
Overall survival (OS)
OS is defined as the time from date of randomization to date of death due to any cause. Patients still alive or lost to follow up will be censored at the time they were last known to be alive.
Time frame: Approximately up to 84 months following first patient enrollment
Relapse-free survival (RFS) after CR/CRi
RFS is defined as time from the date of achievement of CR/CRi until relapse or death from any cause, whichever comes first. Patients still in first CR/CRi and alive or lost to follow up will be censored at the date of last clinical assessment.
Time frame: Approximately up to 60 months following first patient enrollment
Cumulative incidence of relapse (CIR) after CR/CRi
CIR is measured from the date of achievement of CR/CRi until the date of relapse. Patients not known to have relapsed will be censored on the date of last clinical assessment. Patients who died without relapse will be counted as a competing cause of failure.
Time frame: Approximately up to 60 months following first patient enrollment
Cumulative incidence of death (CID) after CR/CRi
CID is measured from the date of achievement of CR/CRi until the date of death from any cause. Patients not known to have died will be censored on the date they were last known to be alive. Patients who experienced relapse in CR/CRi will be counted as competing cause of failure.
Time frame: Approximately up to 60 months following first patient enrollment
Complete remission without minimal residual disease (CRMRD-) rate after induction cycle 2
CRMRD- rate is defined as the percentage of patients who achieved CR or CRi with no evidence of MRD in bone marrow
Time frame: Approximately up to 60 months following first patient enrollment
Frequency and severity of adverse events according to CTCAE version 5.0
Adverse events will be evaluated using the National Cancer Institute's Common Terminology Criteria for AEs (CTCAE) version 5.0
Time frame: Continuously throughout the study, starting from informed consent until 30 days following the last administration of any study drug
CR/CRi rates after induction cycle 1 and 2
CR and CRi are determined by the Investigator based on the European LeukemiaNet (ELN2017) recommended response criteria
Time frame: Approximately up to 60 months following first patient enrollment
CR/CRi rate after remission induction (i.e., CR or CRi as best response during or at completion of induction therapy)
CR+CRi rate after remission induction is defined as the percentage of patients with best response of CR or CRi during or at completion of induction therapy
Time frame: Approximately up to 60 months following first patient enrollment
Time to hematopoietic recovery after each chemotherapy treatment cycle
Time to hematopoietic recovery is defined as the time from the start of the cycle until recovery
Time frame: Approximately up to 60 months following first patient enrollment
EQ-5D-5L visual analogue scale (VAS)
The EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today". Each domain has 5 levels. Each level has a 1 digit number expressing the level selected for that dimension. These levels are summed up and the self-rated health is recorded on a 20 cm vertical, visual analogue scale, with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'.
Time frame: At entry, 1st day of maintenance, every 3 months during the first year of maintenance, every 6 months during the second year of maintenance until relapse or treatment discontinuation (approximately up to 84 months following first patient enrollment)
EORTC-QLQ-C30 global health status/QoL scale.
The EORTC QLQ-C30 is a 30-item questionnaire that assesses 5 functional subdomains (physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning), 1 global health status, 3 symptom subdomains (fatigue, nausea and vomiting and pain) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Estimate the average of the items that contribute to the scale; this is the raw score. a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.
Time frame: At entry, 1st day of maintenance, every 3 months during the first year of maintenance, every 6 months during the second year of maintenance until relapse or treatment discontinuation (approximately up to 84 months following first patient enrollment)
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AU-Hobart TAS-RHOBART
Hobart, Australia
AU-Launceston TAS-LAUNCESTON
Launceston, Australia
AU-Melbourne-ALFRED
Melbourne, Australia
AU-Melbourne-AUSTIN
Melbourne, Australia
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