Clinical Trial: Ibrutinib in Treating Patients With Relapsed Hairy Cell Leukemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase Inhibitor PCI-32765 (Ibrutinib) for Treatment of Relapsed Hairy Cell Leukemia

Brief Summary: This phase II trial studies how well ibrutinib works in treating patients with hairy cell leukemia that has returned after a period of improvement. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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: confirmation of expression BRAFV600E in leukemia cells; pharmacodynamic effects of BTK inhibition on phosphorylated (phospho) ERK regulation, as well as other potential protein kinase targets of ibrutinib (exploratory); serum soluble 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.

OUTLINE:

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.



Original Primary Outcome: Overall response rate (CR and PR) [ Time Frame: 32 weeks ]

Current Secondary Outcome:

  • Expression BRAFV600E in HCL 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.
  • Immunologic outcomes during single agent ibrutinib administration [ Time Frame: Up to 12 months ]
  • 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 ]
    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 ]
  • 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.
  • 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.
  • Protein kinase regulation [ Time Frame: Up to day 29 (day 1 of course 2) ]
    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 ]
  • 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.


Original Secondary Outcome:

  • Frequency and severity of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 2 years ]
  • Progression-free survival (PFS) [ 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 2 years ]
    Kaplan-Meier curves will be used to estimate overall survival and time to next treatment.
  • Overall survival (OS) [ 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 2 years ]
    Kaplan-Meier curves will be used to estimate overall survival and time to next treatment.
  • 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 ]


Information By: National Cancer Institute (NCI)

Dates:
Date Received: April 24, 2013
Date Started: April 2013
Date Completion:
Last Updated: May 18, 2017
Last Verified: May 2017