Phase Ia/IIb study of PHD inhibitor molidustat in combination with IDH1 inhibitor ivosidenib in IDH1-mutated relapsed/refractory AML or MDS/AML patients

Conditions

Adult patients with relapsed or refractory IDH1-mutated AML or relapsed or refractory MDS/AML, who are not eligible for intensive chemotherapy including alloHCT

Brief summary

Phase Ia: Frequency of DLTs during cycle 1 of treatment (up to 42 days)., Phase IIb: Rate of complete remission (CR)within the first 6 months of treatment.

Detailed description

Combined rate of complete remission (CR), CR with partial hematologic recovery (CRh) and incomplete hematologic recovery (CRi) within the first 6 months of treatment., Proportion of patients being transfusion-free for ≥ 8 weeks for erythrocytes and/or platelets during the first 24 weeks., Event-free survival (EFS), Modified EFS, Overall survival (OS), Relapse-free survival (RFS), Cumulative incidence of relapse (CIR) after CR/CRh/CRi., Cumulative incidence of death (CID) after CR/CRh/CRi., CR/CRh/CRi without minimal residual disease (CR/CRh/CRiMRD−) rate at C2D1, C4D1 and C7D1 and EOT (by NGS)., Proportion of patients with ≥4-fold increase of erythropoietin (EPO) over screening and of ≥8-fold decrease of R-2HG concentration in serum on C1D8, C2D1, C4D1 and C7D1., Frequency and severity of (serious) adverse events ac-cording to CTCAE version 5.0., Proportion of patients requiring phlebotomy (hematocrit ≥ 45%)., Day 30 and 60 mortality rates.

Related papers

No related papers found yet.

Interventions

DRUGMUSREDO

DRUGTibsovo 250 mg film-coated tablets

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Design outcomes

Primary

Measure	Time frame
Phase Ia: Frequency of DLTs during cycle 1 of treatment (up to 42 days)., Phase IIb: Rate of complete remission (CR)within the first 6 months of treatment.	—

Secondary

Measure	Time frame
Combined rate of complete remission (CR), CR with partial hematologic recovery (CRh) and incomplete hematologic recovery (CRi) within the first 6 months of treatment., Proportion of patients being transfusion-free for ≥ 8 weeks for erythrocytes and/or platelets during the first 24 weeks., Event-free survival (EFS), Modified EFS, Overall survival (OS), Relapse-free survival (RFS), Cumulative incidence of relapse (CIR) after CR/CRh/CRi., Cumulative incidence of death (CID) after CR/CRh/CRi., CR/CRh/CRi without minimal residual disease (CR/CRh/CRiMRD−) rate at C2D1, C4D1 and C7D1 and EOT (by NGS)., Proportion of patients with ≥4-fold increase of erythropoietin (EPO) over screening and of ≥8-fold decrease of R-2HG concentration in serum on C1D8, C2D1, C4D1 and C7D1., Frequency and severity of (serious) adverse events ac-cording to CTCAE version 5.0., Proportion of patients requiring phlebotomy (hematocrit ≥ 45%)., Day 30 and 60 mortality rates.	—

Measure

Time frame

Combined rate of complete remission (CR), CR with partial hematologic recovery (CRh) and incomplete hematologic recovery (CRi) within the first 6 months of treatment., Proportion of patients being transfusion-free for ≥ 8 weeks for erythrocytes and/or platelets during the first 24 weeks., Event-free survival (EFS), Modified EFS, Overall survival (OS), Relapse-free survival (RFS), Cumulative incidence of relapse (CIR) after CR/CRh/CRi., Cumulative incidence of death (CID) after CR/CRh/CRi., CR/CRh/CRi without minimal residual disease (CR/CRh/CRiMRD−) rate at C2D1, C4D1 and C7D1 and EOT (by NGS)., Proportion of patients with ≥4-fold increase of erythropoietin (EPO) over screening and of ≥8-fold decrease of R-2HG concentration in serum on C1D8, C2D1, C4D1 and C7D1., Frequency and severity of (serious) adverse events ac-cording to CTCAE version 5.0., Proportion of patients requiring phlebotomy (hematocrit ≥ 45%)., Day 30 and 60 mortality rates.

—

Countries

Germany

Outcome results

None listed