AZD6738 for Patients With Progressive MDS or CMML
- Registration Number
- NCT03770429
- Lead Sponsor
- Massachusetts General Hospital
- Brief Summary
This research study is studying a research drug called AZD6738 as a possible treatment for Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia .
- Detailed Description
This is a Phase Ib clinical trial. A Phase I clinical trial tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved AZD6738 as a treatment for any disease.
AZD6738 is a a drug being studied as a potential treatment for individuals with Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia. It targets a specific pathway in cells that repairs damage to DNA, specifically by blocking a protein called ATR. ATR notices when there is injury to DNA, which is the blueprint that allows cells to function and replicate, and works to repair that damage. Studies done in a laboratory setting and cell lines suggest that MDS and CMML cells rely specifically on the ATR pathway to fix DNA damage and survive; by inhibiting ATR with AZD6738, MDS or CMML cells appear to selectively accumulate DNA damage and die, but healthy cells appear to be less sensitive to this target. This suggests that inhibiting ATR may be a way to selectively target MDS or CMML cells.
In this research study, the investigators are looking to first investigate the safety and tolerability of AZD6738. The investigators will also evaluate whether AZD6738 has any effect on tumor growth, measure the activity of AZD6738 in the bone marrow, and study how AZD6738 is cleared by the body.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 52
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AZD6738 AZD6738 Patients will receive AZD6738 orally on a 28-day cycle
- Primary Outcome Measures
Name Time Method Safety of AZD6738 in MDS and CMML (Incidence of dose limiting toxicities) 2 years Incidence of dose limiting toxicities within the first 28 days of treatment, and enumeration of treatment emergent adverse events graded according to CTCAE
- Secondary Outcome Measures
Name Time Method Progression Free Survival Rate 2 years Proportion of patients alive without disease progression at 1 year
Classification of Toxicity 2 years We will describe the frequency and severity of adverse events during treatment.
Overall Survival Rate 2 years Proportion of patients alive at 1 year
Overall Response Rate - splicing factor WT 2 years We will determine the ORR (CR, mCR, PR, HI) as well as stable disease and progressive disease among patients without splicing factor mutations.
Overall Response Rate - splicing factor MUT 2 years We will determine the ORR (CR, mCR, PR, HI) as well as stable disease and progressive disease among patients with splicing factor mutations.
Trial Locations
- Locations (4)
BIDMC
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Washington University
🇺🇸Saint Louis, Missouri, United States