Safety and Tolerability of Oral Clofarabine in Intermediate to High Risk Myelodysplastic Patients
This is a Phase I trial for patients with intermediate or high risk myelodysplastic syndrome (MDS).
The study agent, clofarabine, is produced by Genzyme Pharmaceuticals.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study Evaluating the Safety and Tolerability of Oral Clofarabine in Intermediate to High Risk Myelodysplastic Patients|
- To determine the safety, maximum tolerated dose (MTD) and recommended phase II dose of Clofarabine in patients with myelodysplastic syndrome (MDS). [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
- To determine the efficacy of Clofarabine in patients with MDS [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
- To determine the differences in clofarabine triphosphate levels in cells following clofarabine treatment [ Time Frame: Pre, Day 1: Hourly for 6 hours, Pre Day 5:Hourly for 5 hours ] [ Designated as safety issue: No ]
- Determine the differences in clofarabine plasma levels following clofarabine treatment [ Time Frame: Pre, Day 1: Hourly for 6 hours, Pre Day 5:Hourly for 5 hours ] [ Designated as safety issue: No ]
- Evaluate the effect of clofarabine on DNA methylation [ Time Frame: Pre and Day 1 ] [ Designated as safety issue: No ]
- Estimate post-treatment p53R2levels in patients treated at the MTD (in the expanded cohort) [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||October 2009|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Experimental: Level 1
1 mg daily for 5 consecutive days followed by 23 days off drug
Dose Escalation Schedule - Level 1: 1 mg daily x 5 days (orally) followed by 23 days off drug.
Levels 2, 3, 4 and 5 are: 3, 5, 10 and 15 mg daily x 5 days followed by 23 days off drug.
The specific purpose of the study is to determine the safety, maximum tolerated dose (MTD) and recommended Phase II dose of clofarabine in patients with MDS.
- We will start at a dose of 1 mg daily.
- We will treat a group of 3 patients with clofarabine at that dose level.
- If there are no severe side effects seen at that dose level, then the next group of 3 patients will receive a higher dose.
- Treatment of groups of 3 patients will continue at higher dose levels until severe side-effects are noted.
- If more than 1 of the 3 patients experiences a severe side effect, dosing will be stopped at that level.
- If only one of the three patients experience a severe side effect, then three more patients will be treated, at that dose level and if they too experience severe side effects, then dose escalation will be stopped and the maximum tolerated dose will be determined.
- 10 more patients will be enrolled at the maximum tolerated dose.
- There will be up to 5 dose levels tested.
- We plan to test how much of the drugs are in the patient's blood at different times, and the levels of certain proteins in their blood.
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Wetzler Meir, MD||Roswell Park Cancer Institute|