Dasatinib in Treating Patients With Chronic Lymphocytic Leukemia
|Refractory Chronic Lymphocytic Leukemia Stage I Chronic Lymphocytic Leukemia Stage II Chronic Lymphocytic Leukemia Stage III Chronic Lymphocytic Leukemia Stage IV Chronic Lymphocytic Leukemia||Drug: Dasatinib Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Dasatinib in Chronic Lymphocytic Leukemia in Patients Who Exhibit in Vitro Dasatinib Sensitivity|
- In vitro dasatinib sensitivity in predicting clinical activity [ Time Frame: 8 weeks ]Defined by a decrease in absolute lymphocyte count, as determined by peripheral blood complete blood count (CBC) with differential or by bone marrow examination of 50 % and/or a decrease of detectable total lymph node size or spleen size by 50% (either by clinical examination contrast enhanced computed tomography [CT]). Summarized using descriptive statistics (e.g., proportions for categorical variables, and mean/standard deviation for continuous variables).
- Incidence of adverse events assessed according to the NCI Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years ]Adverse events will be tabulated and summarized according to key reporting criteria (i.e., grade or seriousness, unanticipated, treatment attribution).
- Objective response [ Time Frame: Up to 2 years ]Proportion of patients achieving the endpoint along with its 95% exact binomial confidence interval will be presented.
- Overall survival [ Time Frame: Up to 2 years ]Kaplan-Meier method will be used to estimate the survival curve.
- Progression-free survival [ Time Frame: Up to 2 years ]Kaplan-Meier method will be used to estimate the survival curve.
- Target response rate [ Time Frame: Up to 2 years ]Proportion of patients achieving the endpoint along with its 95% exact binomial confidence interval will be presented.
- Biomarker analysis of SRC, TEC, or BTK family kinase inhibition [ Time Frame: Up to 2 years ]Use of either t-test (normally distributed variables) or Wilcoxon rank sum test (non-normally distributed variables) to determine whether the mean of continuous biomarkers or patient factors (e.g., IC50 dasatinib cytotoxicity, SRC family kinase inhibition level, TEC family kinase inhibition level, disease risk such as the presence or absence of poor risk features as defined in the protocol) are significantly different between responders and non-responders.
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||January 1, 2018|
|Primary Completion Date:||July 12, 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (dasatinib)
Patients receive dasatinib PO QD during course 1 and if tolerated, BID in subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
I. To estimate the biologic target activity of dasatinib in CLL patients found to have pre-treatment in vitro dasatinib cytotoxicity (as defined by a >= 50% decrease in absolute lymphocyte count and/or bone marrow CLL count and/or lymph node or spleen size).
I. To evaluate overall objective response rates per CLL National Cancer Institute (NCI) working group.
II. To determine drug safety and tolerability of dasatinib in patients with CLL.
III. To determine overall (OS) and progression-free survival (PFS).
I. To determine if v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC), Bruton agammaglobulinemia tyrosine kinase (BTK), or tec protein tyrosine kinase (TEC) family kinase inhibition correlates with clinical response.
II. To determine which prognostic subgroups (presence of >= 1 of the following: 11q or 17p deletion; cluster of differentiation [CD]38 or zeta-chain-associated protein kinase 70 [Zap 70] expression; unmutated immunoglobulin heavy chain [IgVH]) respond to dasatinib therapy.
III. To evaluate differences in baseline CLL gene expression between CLL samples that are sensitive or in-sensitive to dasatinib.
IV. To analyze changes in CLL gene expression after dasatinib treatment. V. To evaluate dasatinib pharmacokinetics. VI. To evaluate changes in type I receptor tyrosine kinase-like orphan receptor (ROR-1) expression with dasatinib treatment.
VII. To correlate response to pre-clinical IC50 in the presence/absence of HS-5 conditioned media.
VIII. To explore role of possible kinase mutations related to dasatinib response.
IX. To measure chemokines before and during treatment.
Patients receive dasatinib orally (PO) once daily (QD) during course 1 and if tolerated, twice daily (BID) in subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01441882
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239|
|Principal Investigator:||Stephen Spurgeon||OHSU Knight Cancer Institute|