Alvespimycin Hydrochloride in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-Cell Prolymphocytic Leukemia
This phase I trial is studying the side effects and the best dose of alvespimycin hydrochloride in treating patients with relapsed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or B-cell prolymphocytic leukemia (B-PLL). Drugs used in chemotherapy, such as alvespimycin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing
B-cell Chronic Lymphocytic Leukemia
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Drug: alvespimycin hydrochloride
Genetic: DNA analysis
Other: diagnostic laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
|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)|
- MTD [ Time Frame: Baseline, days 1 and 8 during cycles 1-6, during off treatment, and then every 3 months for 2 years ] [ Designated as safety issue: Yes ]Defined as the maximum dose level where at most 1 of 6 patients experience DLT.
- DLT [ Time Frame: Baseline, days 1 and 8 during cycles 1-6, during off treatment, and then every 3 months for 2 years ] [ Designated as safety issue: Yes ]Graded using the Cancer Therapy Evaluation Program (CTEP) active version of the National Cancer Institute Common Toxicity Criteria (CTCAE) with the exception of hematological toxicity.
- Pharmacokinetics [ Time Frame: Days 1, 2, 3, 4, 8, 11 ] [ Designated as safety issue: No ]Analyzed to assess plasma drug concentrations.
- Pharmacodynamic markers [ Time Frame: Days 1 and 8 of cycle 1, and then day 1 of cycle 2 ] [ Designated as safety issue: No ]Evaluating serial changes in AKT, IKK, FoxD3, EPHA7 and ID4 at the RP2D.
- Pharmacogenetics [ Time Frame: Baseline and day 1 ] [ Designated as safety issue: No ]
|Study Start Date:||May 2010|
|Primary Completion Date:||February 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:Genetic: DNA analysis 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.
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Jeffrey Jones||Ohio State University|