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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT06465953
Registration number
NCT06465953
Ethics application status
Date submitted
14/06/2024
Date registered
20/06/2024
Date last updated
10/07/2025
Titles & IDs
Public title
Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an IDH1 Mutation
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Scientific title
A Phase 3, Multicenter, Open Label, Randomized, Non-comparative Two-arm Study of Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Adult Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an Isocitrate Dehydrogenase-1 (IDH1) Mutation (PyramIDH Study)
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Secondary ID [1]
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2023-510155-37
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Secondary ID [2]
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S095031-178
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Universal Trial Number (UTN)
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Trial acronym
PyramIDH
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS)
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Myelodysplastic Syndromes (MDS)
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Condition category
Condition code
Blood
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Haematological diseases
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Blood
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Other blood disorders
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Other
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Research that is not of generic health relevance and not applicable to specific health categories listed above
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Ivosidenib
Treatment: Drugs - Azacitidine
Experimental: Ivosidenib monotherapy -
Experimental: Azacitidine monotherapy -
Treatment: Drugs: Ivosidenib
Two 250 mg tablets, totaling 500 mg, administered orally once daily until disease relapse or progression, unacceptable toxicity, confirmed pregnancy, undergoing HSCT, death, withdrawal of consent, lost to follow-up, or Sponsor ending the study, whichever occurs first.
Treatment: Drugs: Azacitidine
Azacitidine 75mg/m\^2/day administered by subcutaneous (SC) or intravenous (IV) injection for 1 week (7 days) of each 4-week (28 day) treatment cycle until disease relapse or progression, unacceptable toxicity, confirmed pregnancy, undergoing HSCT, death, withdrawal of consent, lost to follow-up, or Sponsor ending the study, whichever occurs first.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of participants achieving CR and PR at 4 months
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Assessment method [1]
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Complete remission (CR) or Partial remission (PR) as per International Working Group (IWG) 2006 criteria
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Timepoint [1]
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Through 4 months after starting treatment
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Secondary outcome [1]
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Overall Response (OR) rate per IWG 2023 criteria
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Assessment method [1]
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Defined as CR (or CR equivalent) + PR + CRL + CRh + hematological improvement (HI)
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Timepoint [1]
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Through the end of the study (approximately 4 years)
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Secondary outcome [2]
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Event-free survival (EFS)
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Assessment method [2]
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Defined as the date of randomization to the date of first documented confirmed relapse /progression /death, whichever occurs first
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Timepoint [2]
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Through the end of the study (approximately 4 years)
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Secondary outcome [3]
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Overall Survival (OS)
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Assessment method [3]
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Defined as the time from randomization to the date of death due to any cause. Participants who are alive at the analysis cutoff date will be censored at the date they were last known to be alive.
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Timepoint [3]
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Through the end of the study (approximately 4 years)
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Secondary outcome [4]
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Duration of CR and PR
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Assessment method [4]
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Among participants who achieved CR+PR per IWG 2006 criteria
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Timepoint [4]
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Through the end of the study (approximately 4 years)
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Secondary outcome [5]
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Time to CR and PR
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Assessment method [5]
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Defined as time from the date of the randomization to the date of CR+PR, among participants who achieve CR+PR based on IWG 2006 Response Criteria
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Timepoint [5]
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Through the end of the study (approximately 4 years)
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Secondary outcome [6]
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Acute myeloid leukemia (AML) transformation rate
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Assessment method [6]
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Timepoint [6]
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Through the end of the study (approximately 4 years)
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Secondary outcome [7]
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Time to transfusion independence (TTTI)
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Assessment method [7]
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Defined as time from date of randomization to date transfusion independence (TI) is first observed (Day 1 of a = 56 days period without a transfusion), among participants who are baseline transfusion dependent and have achieved post-baseline TI. In the event a participant had more than one = 56-day period, which met TI criteria, the earliest period will be used in analysis.
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Timepoint [7]
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Through the end of the study (approximately 4 years)
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Secondary outcome [8]
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Duration of transfusion independence (DOTI)
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Assessment method [8]
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Among participants who have achieved post-baseline TI, DOTI will be calculated as the time from the date TI is first observed (Day 1 of a = 56-day period without a transfusion) until the day before the participants had a subsequent transfusion.
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Timepoint [8]
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Through the end of the study (approximately 4 years)
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Secondary outcome [9]
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Transfusion independence rate
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Assessment method [9]
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Timepoint [9]
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Through the end of the study (approximately 4 years)
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Secondary outcome [10]
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Change from baseline in Quality of life (QOL) based on the QUALMS score
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Assessment method [10]
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Quality of Life in Myelodysplasia Scale (QUALMS) scores range from 0 to 100, with a higher score representing a better QOL.
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Timepoint [10]
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Through the Event Free Survival Follow up (approximately 4 years)
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Secondary outcome [11]
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Change from baseline in health economic outcomes measures based on EQ-5D-5L score
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Assessment method [11]
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Health economic outcomes measures as assessed by the 5-level EuroQol five dimensions questionnaire (EQ-5D-5L) scores range from 5 to 25 with a higher number representing a worse health status.
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Timepoint [11]
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Through the Event Free Survival Follow up (approximately 4 years)
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Secondary outcome [12]
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Number of participants who proceed to hematopoietic stem cell transplantation (HSCT)
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Assessment method [12]
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Timepoint [12]
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Through the end of the study (approximately 4 years)
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Secondary outcome [13]
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Ivosidenib plasma concentrations
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Assessment method [13]
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For participants receiving ivosidenib monotherapy
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Timepoint [13]
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Through Cycle 22 (each cycle is 28 days)
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Secondary outcome [14]
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2-HG plasma concentrations
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Assessment method [14]
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For participants receiving ivosidenib monotherapy
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Timepoint [14]
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Through Cycle 22 (each cycle is 28 days)
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Secondary outcome [15]
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Number of participants achieving CR and PR at 6 months as per IWG 2006 criteria
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Assessment method [15]
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Timepoint [15]
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Through 6 months after starting treatment
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Secondary outcome [16]
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Number of participants achieving CR and PR at 6 months as per IWG 2023 criteria
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Assessment method [16]
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Timepoint [16]
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Through 6 months after starting treatment
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Secondary outcome [17]
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Number of participants achieving CR and PR at 4 months as per IWG 2023 criteria
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Assessment method [17]
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Timepoint [17]
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Through 4 months after starting treatment
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Secondary outcome [18]
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Number of adverse events (AEs) and serious adverse events (SAEs)
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Assessment method [18]
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Timepoint [18]
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Through the Safety Follow-up Visit (30-35 days after discontinuation of treatment)
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Eligibility
Key inclusion criteria
* Diagnosis of HMA naive IDH1 R132 mutated MDS defined according to WHO criteria (5th edition):
* Moderate high, high and very high-risk MDS per IPSS-M score will be eligible regardless of blood counts and with blast counts 0-19%.
* Low and moderate low-risk MDS per IPSS-M score must:
* Have cytopenias related to MDS, defined as: <100 platelets/microliter, or absolute neutrophil count (ANC) <1000/mm3, or hemoglobin <10g/dL AND
* Have a blast count between 5-19% AND
* Be eligible for HMA therapy (very low risk participants are to be excluded)
* Locally or centrally confirmed IDH1 R132 C/G/H/L/S mutation
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Received prior anticancer/disease modifying treatment for MDS (including HMA's, cytotoxic chemotherapy, investigational agents, bcl-2 inhibitor based-regimens, hematopoietic stem cell transplant (HSCT), IDH1 inhibitors). For LR-MDS patients, prior treatment with growth factors, luspatercept, lenalidomide, and imetelstat are allowed.
* >20% blasts by morphology or immunohistochemistry on screening bone marrow aspirate/biopsy
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
3/12/2024
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/12/2028
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Actual
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Sample size
Target
48
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Monash Health - Clayton
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Recruitment hospital [2]
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Northern Health - Epping
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Recruitment hospital [3]
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Liverpool Hospital - Liverpool
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Recruitment hospital [4]
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Sir Charles Gairdner Hospital - Nedlands
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Recruitment hospital [5]
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Calvary Mater Newcastle - Waratah
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Recruitment postcode(s) [1]
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3168 - Clayton
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Recruitment postcode(s) [2]
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3076 - Epping
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Recruitment postcode(s) [3]
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2170 - Liverpool
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Recruitment postcode(s) [4]
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6009 - Nedlands
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Recruitment postcode(s) [5]
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2298 - Waratah
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Recruitment outside Australia
Country [1]
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United States of America
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Colorado
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United States of America
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Illinois
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United States of America
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Massachusetts
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Ohio
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Oregon
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Texas
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France
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Nantes
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France
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Nice
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France
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Paris
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France
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Pessac
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France
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Toulouse
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France
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Vandœuvre-lès-Nancy
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Germany
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Dresden
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Germany
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Düsseldorf
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Germany
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Göttingen
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Germany
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Leipzig
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Germany
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Munich
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Italy
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Ancona
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Italy
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Bologna
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Italy
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Firenze
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Italy
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Milano
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Italy
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Pavia
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Italy
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Roma
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Italy
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Torino
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Japan
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Eiheiji-cho 670-8540 Himeji
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Japan
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Higashi-ku, Fukuoka-city, Fukuoka
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Japan
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Himeji-city, Hyogo
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Japan
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Isehara-city, Kanagawa
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Japan
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Musashino-city, Tokyo
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Netherlands
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Amsterdam
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Netherlands
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Groningen
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Spain
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Badalona
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Pamplona
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Spain
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Salamanca
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Spain
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Sevilla
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Spain
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Valencia
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United Kingdom
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Edinburgh
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United Kingdom
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Leeds
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United Kingdom
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London
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United Kingdom
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Oxford
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United Kingdom
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State/province [45]
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Torquay
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Funding & Sponsors
Primary sponsor type
Other
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Name
Institut de Recherches Internationales Servier
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Address
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Other collaborator category [1]
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Commercial sector/industry
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Name [1]
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Servier Bio-Innovation LLC
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
This study will enroll participants with myelodysplastic syndromes (MDS) with an Isocitrate dehydrogenase protein, 1 (IDH1) mutation, who have not received treatment with a hypomethylating agent previously. Participants will be randomized to receive either ivosidenib (IVO) alone or azacitidine (AZA) alone. IVO will be administered daily throughout the 28-day treatment cycle and AZA will be administered for the first 7 days of each 28-day cycle. Study visits will be conducted every week during Cycle 1 (Days 1, 8, 15, and 22), and Day 1 of each cycle thereafter. After the last dose of treatment, participants will attend an safety follow-up visit and participants will be followed to assess overall survival. Study visits may include a bone marrow aspirate, physical exam, echocardiogram (ECHO), electrocardiogram (ECG), blood and urine analysis, and questionnaires.
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Trial website
https://clinicaltrials.gov/study/NCT06465953
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
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Address
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Country
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Phone
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+33 1 55 72 60 00
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies:
* used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
* where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.
In addition, access can be requested for all interventional clinical studies in patients:
* sponsored by Servier
* with a first patient enrolled as of 1 January 2004 onwards
* for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
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When will data be available (start and end dates)?
After Marketing Authorization in EEA or US if the study is used for the approval.
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Available to whom?
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: http://clinicaltrials.servier.com/
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT06465953
Download to PDF