Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an IDH1 Mutation
- Conditions
- Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS)Myelodysplastic Syndromes (MDS)
- Interventions
- Registration Number
- NCT06465953
- Lead Sponsor
- Institut de Recherches Internationales Servier
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 48
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Azacitidine monotherapy Azacitidine - Ivosidenib monotherapy Ivosidenib -
- Primary Outcome Measures
Name Time Method Number of participants achieving CR and PR at 4 months Through 4 months after starting treatment Complete remission (CR) or Partial remission (PR) as per International Working Group (IWG) 2006 criteria
- Secondary Outcome Measures
Name Time Method Overall Response (OR) rate per IWG 2023 criteria Through the end of the study (approximately 4 years) Defined as CR (or CR equivalent) + PR + CRL + CRh + hematological improvement (HI)
Event-free survival (EFS) Through the end of the study (approximately 4 years) Defined as the date of randomization to the date of first documented confirmed relapse /progression /death, whichever occurs first
Overall Survival (OS) Through the end of the study (approximately 4 years) 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.
Duration of CR and PR Through the end of the study (approximately 4 years) Among participants who achieved CR+PR per IWG 2006 criteria
Time to CR and PR Through the end of the study (approximately 4 years) 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
Acute myeloid leukemia (AML) transformation rate Through the end of the study (approximately 4 years) Time to transfusion independence (TTTI) Through the end of the study (approximately 4 years) 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.
Duration of transfusion independence (DOTI) Through the end of the study (approximately 4 years) 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.
Transfusion independence rate Through the end of the study (approximately 4 years) Change from baseline in Quality of life (QOL) based on the QUALMS score Through the Event Free Survival Follow up (approximately 4 years) Quality of Life in Myelodysplasia Scale (QUALMS) scores range from 0 to 100, with a higher score representing a better QOL.
Change from baseline in health economic outcomes measures based on EQ-5D-5L score Through the Event Free Survival Follow up (approximately 4 years) 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.
Number of participants who proceed to hematopoietic stem cell transplantation (HSCT) Through the end of the study (approximately 4 years) Ivosidenib plasma concentrations Through Cycle 22 (each cycle is 28 days) For participants receiving ivosidenib monotherapy
2-HG plasma concentrations Through Cycle 22 (each cycle is 28 days) For participants receiving ivosidenib monotherapy
Number of participants achieving CR and PR at 6 months as per IWG 2006 criteria Through 6 months after starting treatment Number of participants achieving CR and PR at 6 months as per IWG 2023 criteria Through 6 months after starting treatment Number of participants achieving CR and PR at 4 months as per IWG 2023 criteria Through 4 months after starting treatment Number of adverse events (AEs) and serious adverse events (SAEs) Through the Safety Follow-up Visit (30-35 days after discontinuation of treatment)
Trial Locations
- Locations (1)
University of Fukui Hospital
🇯🇵Yoshida-gun, Eiheiji-cho 670-8540 Himeji, Japan