Ibrutinib in Treating Patients With Relapsed Hairy Cell Leukemia
Hairy Cell Leukemia
Hairy Cell Leukemia Variant
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase Inhibitor PCI-32765 (Ibrutinib) for Treatment of Relapsed Hairy Cell Leukemia|
- Overall response rate (CR and PR) [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]Calculated as the proportion of patients who achieve a PR or CR to therapy within the first 32 weeks of therapy divided by the total number of evaluable patients.
- Expression BRAFV600E in HCL cells [ Time Frame: Baseline ] [ Designated as safety issue: No ]Markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group (e.g. responders vs. not). Graphical analyses will be largely used to assess potential patterns and relationships; e.g. side-by-side boxplots to assess differences in continuous marker levels between those with vs. without the clinical improvement.
- Immunologic outcomes during single agent ibrutinib administration [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
- Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 [ Time Frame: Up to 30 days after treatment ] [ Designated as safety issue: Yes ]Frequency and severity of adverse events and tolerability of the regimen in each of the patient groups will be collected and summarized by descriptive statistics.
- MRD level following maximal response [ Time Frame: Up to 30 days after completing study treatment ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: From the date of study registration to the date of event or the date of last follow-up if no event has occurred, assessed up to 3 years ] [ Designated as safety issue: No ]Kaplan-Meier curves will be used to estimate overall survival and time to next treatment.
- Progression-free survival [ Time Frame: From the date of study registration to the date of event or the date of last follow-up if no event has occurred, assessed up to 3 years ] [ Designated as safety issue: No ]Kaplan-Meier curves will be used to estimate overall survival and time to next treatment.
- Protein kinase regulation [ Time Frame: Up to day 29 (day 1 of course 2) ] [ Designated as safety issue: No ]Pharmacodynamic effects of BTK inhibition on phospo ERK regulation, as well as other possible protein kinase targets of ibrutinib including B lymphoid tyrosine kinase and BMX non-receptor tyrosine kinase/Etk will be assessed.
- Rate of molecular remission (MRD-negative CR) defined as resolution of all detectable disease below the limits of detection by immunohistochemistry and 4-color flow cytometry assay [ Time Frame: Up to 32 weeks ] [ Designated as safety issue: No ]
- Serum soluble IL-2 receptor level [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group (e.g. responders vs. not). Graphical analyses will be largely used to assess potential patterns and relationships; e.g. side-by-side boxplots to assess differences in continuous marker levels between those with vs. without the clinical improvement.
- Pharmacokinetic (PK) parameters [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on days 1 and 8 of course 1 and predose and 2 hours on days 15 and 22 of course 1 and day 1 of course 2 ] [ Designated as safety issue: No ]Computed using non-compartmental and compartmental methods. Graphical analyses will be used as well as repeated measure models (linear or nonlinear mixed models, generalized estimating equation) to assess the PK markers in relation to clinical treatment outcomes.
|Study Start Date:||April 2013|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (ibrutinib)
Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
I. To determine the overall response rate (complete response [CR] and partial response [PR]) of hairy cell leukemia (HCL) at 32 weeks after beginning therapy with single-agent ibrutinib.
I. To characterize the toxicity and tolerability of single-agent ibrutinib when administered to patients with HCL.
II. To characterize the progression-free (PFS) and overall survival (OS) of single- agent ibrutinib when administered to patients with HCL.
III. To determine the rate of molecular remission (minimal residual disease [MRD]-negative CR) among all patients, defined as resolution of all detectable disease below the limits of detection by immunohistochemistry and/or 4-color flow cytometry assay at 32 weeks after beginning ibrutinib therapy.
IV. To characterize immunologic outcomes during single agent ibrutinib administration.
V. To explore the effect of PCI-32765 (ibrutinib) on traditional and new biomarkers in HCL including: confirmation of expression v-raf murine sarcoma viral oncogene homolog B V600E mutation (BRAFV600E) in leukemia cells; pharmacodynamic effects of Bruton agammaglobulinemia tyrosine kinase (BTK) inhibition on phospho extracellular signal-regulated kinase (ERK) regulation, as well as other potential protein kinase targets of ibrutinib (exploratory); serum soluble interleukin (IL)-2 receptor correlation with response to ibrutinib therapy; documentation of and quantification of minimal residual disease following maximal response, with flow cytometric analysis and immunohistochemical stains of the bone marrow, as predictors of remission duration after ibrutinib therapy.
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01841723
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Robert J. Kreitman 301-496-6947 firstname.lastname@example.org|
|Principal Investigator: Robert J. Kreitman|
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Daniel J. DeAngelo 617-632-2645 email@example.com|
|Principal Investigator: Daniel J. DeAngelo|
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Charles A. Schiffer 313-576-8720 firstname.lastname@example.org|
|Principal Investigator: Charles A. Schiffer|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Timothy G. Call 507-538-0591 email@example.com|
|Principal Investigator: Timothy G. Call|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Jeffrey A. Jones 614-293-9165 Jeffrey.firstname.lastname@example.org|
|Principal Investigator: Jeffrey A. Jones|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Farhad Ravandi-Kashani 713-745-0394 email@example.com|
|Principal Investigator: Farhad Ravandi-Kashani|
|Principal Investigator:||Jeffrey Jones||Ohio State University Comprehensive Cancer Center|