Ibrutinib in Treating Patients With Relapsed Hairy Cell Leukemia
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|ClinicalTrials.gov Identifier: NCT01841723|
Recruitment Status : Recruiting
First Posted : April 26, 2013
Last Update Posted : August 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|Hairy Cell Leukemia Hairy Cell Leukemia Variant||Drug: Ibrutinib||Phase 2|
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 ibrutinib (PCI-32765) on traditional and new biomarkers in HCL including:
Va. Confirmation of expression BRAFV600E in leukemia cells Vb. Pharmacodynamic effects of BTK inhibition on phosphorylated (phospho) ERK regulation, as well as other potential protein kinase targets of ibrutinib (exploratory) Vc. Serum soluble IL-2 receptor correlation with response to ibrutinib therapy Vd. 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. Cycles repeat every 28 days for up to 8 cycles if lack of response to therapy, up to 12 cycles if failure to achieve an objective response (CR/PR), or continually at per physician discretion in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase Inhibitor PCI-32765 (Ibrutinib) for Treatment of Relapsed Hairy Cell Leukemia|
|Actual Study Start Date :||April 1, 2013|
|Estimated Primary Completion Date :||December 31, 2019|
Experimental: Treatment (ibrutinib)
Patients receive ibrutinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Overall response rate (complete response [CR] and partial response [PR]) [ Time Frame: 32 weeks ]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.
- Incidence of adverse events [ Time Frame: Up to 30 days after treatment ]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 and will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
- 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 ]Kaplan-Meier curves will be used to estimate overall survival and time to next treatment.
- 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 ]Kaplan-Meier curves will be used to estimate overall survival and time to next treatment.
- Rate of molecular remission (minimal residual disease [MRD]-negative CR) [ Time Frame: Up to 32 weeks ]Defined as resolution of all detectable disease below the limits of detection by immunohistochemistry and 4-color flow cytometry assay will be examined.
- Immunologic outcomes during single agent ibrutinib administration [ Time Frame: Up to 12 months ]
- Expression BRAFV600E in hairy cell leukemia cells [ Time Frame: Baseline ]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.
- Protein kinase regulation [ Time Frame: Up to day 29 (day 1 of cycle 2) ]Pharmacodynamic effects of BTK inhibition on phosphorylated 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.
- Serum soluble IL-2 receptor level [ Time Frame: Up to 3 years ]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.
- MRD level following maximal response [ Time Frame: Up to 30 days after completing study treatment ]Will be with flow cytometric analysis and immunohistochemical stains of the bone as predictor of remission duration after ibrutinib therapy.
- Pharmacokinetic (PK) parameters [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on days 1 and 8 of cycle 1 and predose and 2 hours on days 15 and 22 of cycle 1 and day 1 of cycle 2 ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01841723
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Robert J. Kreitman 301-451-5765 email@example.com|
|Principal Investigator: Robert J. Kreitman|
|United States, Michigan|
|Wayne State University/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|
|Mayo Clinic||Active, not recruiting|
|Rochester, Minnesota, United States, 55905|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Kerry A. Rogers 800-293-5066|
|Principal Investigator: Kerry A. Rogers|
|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:||Kerry A Rogers||Ohio State University Comprehensive Cancer Center|