Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06577441
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-28
Brief Title:
Testing the Addition of an IDH2 Inhibitor Enasidenib to Usual Treatment Cedazuridine-Decitabine for Higher-Risk Myelodysplastic Syndrome MDS With IDH2 Mutation A MyeloMATCH Treatment Trial
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Randomized Phase II Trial of Enasidenib-Based Therapies Versus Cedazuridine-Decitabine in Higher-Risk IDH2-Mutated Myelodysplastic Syndrome A MyeloMATCH Treatment Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II MyeloMATCH treatment trial compares the usual treatment of cedazuridine-decitabine ASTX727 to the combination treatment of ASTX727 and enasidenib in treating patients with higher-risk IDH2-mutated myelodysplastic syndrome MDS ASTX727 is a combination of two drugs decitabine and cedazuridine Cedazuridine is in a class of medications called cytidine deaminase inhibitors It prevents the breakdown of decitabine making it more available in the body so that decitabine will have a greater effect Decitabine is in a class of medications called hypomethylation agents It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow Enasidenib is an enzyme inhibitor that may stop the growth of cells by blocking some of the enzymes needed for cell growth Giving ASTX727 in combination with enasidenib may be effective in treating patients with higher-risk IDH2-mutated MDS
Detailed Description:
PRIMARY OBJECTIVE
I To compare the complete remission CR rate of enasidenib decitabine and cedazuridine ASTX727 and ASTX727 monotherapy in patients with higher-risk IDH2-mutated MDS using International Working Group 2023 IWG2023 response criteria
SECONDARY OBJECTIVES
I To estimate the median event-free survival EFS at designated time points 18 months for each treatment arm
II To estimate the median overall survival OS at designated time points 18 months for each treatment arm
III To estimate the frequency and severity of toxicities with each regimen in this patient population
IV To estimate the median time to response for each treatment arm V To estimate the median duration of response for each treatment arm VI To estimate the IDH2 variant allele frequency VAF reduction for each treatment arm
VII To estimate the rate of allogeneic hematopoietic cell transplantation for each treatment arm
VIII To compare rates of partial response PR CR with limited count recovery CRL CR with partial count recovery CRh and hematologic improvement HI using IWG 2023 response criteria between treatment arms
IX To compare the measurable residual disease MRD kinetics by flow cytometry and next generation sequencing NGS at designated time points at the end of cycle 4 6 and to assess any correlation with clinical outcomes eg CR EFS OS
EXPLORATORY OBJECTIVES
I To estimate CR rate median EFS and median OS in patients treated with ASTX727 monotherapy that crossover to the treatment arm with ASTX727 enasidenib after 6 cycles if CR is not achieved
II To estimate CR rate median EFS and median OS for patients based on Molecular International Prognostic Scoring System IPSS-M prognostic risk score at diagnosis stratified for score level
III To estimate concordance between centrally-performed molecular studies and cytogenetics to those done locally
OUTLINE Patients are randomized to 1 of 2 arms
ARM A Patients receive ASTX727 orally PO once daily QD on days 1-5 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients who do not achieve a CR CRL or CRh at the end of cycle 6 may cross-over to Arm B Patients who experience CR PR or stable disease SD any time after 4 cycles of treatment may be reassessed in order to go to a higher myeloMATCH tier assignment or to Tier Advancement Pathway TAP Patients also undergo bone marrow biopsy and aspiration throughout the study Patients may also undergo optional buccal swab on study andor optional additional bone marrow aspiration and blood sample collection on study and at disease progression
ARM B Patients receive ASTX727 PO QD on days 1-5 and enasidenib PO QD on days 1-28 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients who experience CR PR or SD any time after 4 cycles of treatment may be reassessed in order to go to a higher myeloMATCH tier assignment or to TAP Patients also undergo bone marrow biopsy and aspiration throughout the study Patients may also undergo optional buccal swab on study andor optional additional bone marrow aspiration and blood sample collection on study and at disease progression
After completion of study treatment patients are followed up every 6 months for up to 5 years after registration
I To compare the complete remission CR rate of enasidenib decitabine and cedazuridine ASTX727 and ASTX727 monotherapy in patients with higher-risk IDH2-mutated MDS using International Working Group 2023 IWG2023 response criteria
SECONDARY OBJECTIVES
I To estimate the median event-free survival EFS at designated time points 18 months for each treatment arm
II To estimate the median overall survival OS at designated time points 18 months for each treatment arm
III To estimate the frequency and severity of toxicities with each regimen in this patient population
IV To estimate the median time to response for each treatment arm V To estimate the median duration of response for each treatment arm VI To estimate the IDH2 variant allele frequency VAF reduction for each treatment arm
VII To estimate the rate of allogeneic hematopoietic cell transplantation for each treatment arm
VIII To compare rates of partial response PR CR with limited count recovery CRL CR with partial count recovery CRh and hematologic improvement HI using IWG 2023 response criteria between treatment arms
IX To compare the measurable residual disease MRD kinetics by flow cytometry and next generation sequencing NGS at designated time points at the end of cycle 4 6 and to assess any correlation with clinical outcomes eg CR EFS OS
EXPLORATORY OBJECTIVES
I To estimate CR rate median EFS and median OS in patients treated with ASTX727 monotherapy that crossover to the treatment arm with ASTX727 enasidenib after 6 cycles if CR is not achieved
II To estimate CR rate median EFS and median OS for patients based on Molecular International Prognostic Scoring System IPSS-M prognostic risk score at diagnosis stratified for score level
III To estimate concordance between centrally-performed molecular studies and cytogenetics to those done locally
OUTLINE Patients are randomized to 1 of 2 arms
ARM A Patients receive ASTX727 orally PO once daily QD on days 1-5 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients who do not achieve a CR CRL or CRh at the end of cycle 6 may cross-over to Arm B Patients who experience CR PR or stable disease SD any time after 4 cycles of treatment may be reassessed in order to go to a higher myeloMATCH tier assignment or to Tier Advancement Pathway TAP Patients also undergo bone marrow biopsy and aspiration throughout the study Patients may also undergo optional buccal swab on study andor optional additional bone marrow aspiration and blood sample collection on study and at disease progression
ARM B Patients receive ASTX727 PO QD on days 1-5 and enasidenib PO QD on days 1-28 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients who experience CR PR or SD any time after 4 cycles of treatment may be reassessed in order to go to a higher myeloMATCH tier assignment or to TAP Patients also undergo bone marrow biopsy and aspiration throughout the study Patients may also undergo optional buccal swab on study andor optional additional bone marrow aspiration and blood sample collection on study and at disease progression
After completion of study treatment patients are followed up every 6 months for up to 5 years after registration
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None