Phase I/II Study of a Combination of Decitabine and Cedazuridine (ASTX727) and ASTX029, an ERK Inhibitor, for Patients With RAS Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms

Myeloproliferative Neoplasm Clinical Trial

Official title:
Phase I/II Study of a Combination of Decitabine and Cedazuridine (ASTX727) and ASTX029, an ERK Inhibitor, for Patients With RAS Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms

Status Not yet recruiting

Clinical Trial Summary

The goal of Part 1 of this clinical research study is to find the highest tolerable dose of ASTX029 that can be given in combination with ASTX727 to participants who have RAS-mutant MDS or MDS/MPN. The goal of Part 2 of this clinical research study is to learn if the dose of ASTX029 found in Part 1 can help to control the disease when used in combination with ASTX727.

Clinical Trial Description

Primary Objectives: - Phase 1 dose escalation: to determine safety, tolerability and MTD of ASTX029 in RAS mutant MDS, CMML and other MDS/MPN - Phase 2 dose expansion: to determine the safety, tolerability and overall response rate (ORR) of ASTX727 in combination with ASTX029 in RAS mutant MDS, CMML and other MDS/MPN - Incidence of AEs, MTD and changes in clinical laboratory values. - Measures of efficacy: overall response rate (ORR) defined as sum of CR + complete cytogenetic remission + partial remission + marrow response + clinical benefit for MDS/MPN and defined as CR + mCR + PR + HI in MDS Secondary Objectives: - To determine other efficacy outcomes such as duration of response, leukemia-free survival (LFS), progression-free survival (PFS) and overall survival (OS). - To evaluate differences in response and efficacy outcomes by MDS/MPN IWG response criteria based on disease subtypes and genomic features. - Correlative studies - To evaluate changes in clonal composition and VAF of identified mutations with therapy. - To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of ASTX029 and the combination of ASTX727 with ASTX029 in patients with RAS mutant MDS, CMML and other MDS/MPN ;

Study Design

Related Conditions & MeSH terms

Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Myeloproliferative Neoplasm
Neoplasms
Preleukemia
Syndrome

Clinical Trial Details

NCT number	NCT06284460
Study type	Interventional
Source	M.D. Anderson Cancer Center
Contact	Guillermo Montalban Bravo, MD
Phone	(713) 794-3604
Email	gmontalban1@mdanderson.org
Status	Not yet recruiting
Phase	Phase 1/Phase 2
Start date	July 31, 2024
Completion date	December 1, 2027

View Details

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