Alvespimycin Hydrochloride in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-Cell Prolymphocytic Leukemia
|B-cell Chronic Lymphocytic Leukemia Prolymphocytic Leukemia Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia||Drug: alvespimycin hydrochloride Other: diagnostic laboratory biomarker analysis Other: pharmacogenomic studies Other: pharmacological study||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of the Hsp90 Inhibitor 17-DMAG (Alvespimycin) in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), and B-cell Prolymphocytic Leukemia (B-PLL)|
- Maximum tolerated dose of 17-DMAG [ Time Frame: 21 days ]Defined as the maximum dose level where at most 1 of 6 patients experience dose-limiting toxicity.
|Study Start Date:||May 2010|
|Study Completion Date:||June 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive alvespimycin hydrochloride IV over 60 minutes on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: alvespimycin hydrochloride
Other Names:Other: diagnostic laboratory biomarker analysis Other: pharmacogenomic studies
Other Name: Pharmacogenomic StudyOther: pharmacological study
Other Name: pharmacological studies
I. To determine the maximum tolerated dose (MTD) of 17-DMAG in patients with relapsed CLL/SLL and B-PLL.
II. To define the dose limiting toxicity (DLT) of 17-DMAG in patients with relapsed CLL/SLL and B-PLL.
I. To assess preliminary efficacy of 17-DMAG in patients with relapsed CLL/SLL and B-PLL.
II. To determine the pharmacokinetics of 17-DMAG in patients with relapsed CLL/SLL and B-PLL.
III. To determine the feasibility of measuring pharmacodynamic markers of 17-DMAG including the Hsp90 client proteins Akt and IKK-alpha/IKK-beta.
IV. To determine if FoxD3 and downstream genes such as EPHA7 and ID4 are re-expressed in CLL cells following treatment with 17-DMAG.
V. To correlate pharmacokinetic features of 17-DMAG with response, toxicity and pharmacodynamic endpoints.
VI. To correlate risk parameters such as ZAP-70 with response to 17-DMAG.
OUTLINE: This is a dose-escalation study.
Patients receive alvespimycin hydrochloride intravenously (IV) over 60 minutes on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed every 3 months for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01126502
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Jeffrey Jones||Ohio State University|