PCI-32765 (Ibrutinib) in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-cell Prolymphocytic Leukemia
This is a Phase II, single institution open-label, non-randomized monotherapy study to evaluate the clinical efficacy and durable disease control of PCI-32765 administered to patients with relapsed/refractory CLL/SLL/PLL of all risk categories with patients having deletion 17p13 independently evaluated.
Recurrent Small Lymphocytic Lymphoma
Refractory/Relapsed Chronic Lymphocytic Leukemia
Other: Correlative laboratory samples
Other: quality of life assessment
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765(Ibrutinib), in Relapsed and Refractory Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) and B-cell Prolymphocytic Leukemia (B-PLL)|
- Determine the 2 year progression-free survival (PFS) of single agent PCI-32765 in patients with relapsed and refractory CLL. [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]We will summarize our findings for this endpoint independently as well within each cohort (del17p vs other cytogenetic groups). We will evaluate the proportion of patients who are progression-free and alive at two years or have gone on to transplant (treatment successes) over the total number of evaluable patients; eligible patients who received at least one dose of therapy are considered evaluable. Assuming that the number of treatment successes as defined above is binomially distributed, we will also include 95% binomial confidence intervals for the estimates corresponding to each cohort.
- Overall response rate (ORR), duration of response (DOR) overall survival (OS),assessed using the Revised International Workshop on Chronic Lymphocytic Leukemia (IWCLL) working group guidelines [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]Time from date at which the patient's objective status is first noted to be a response to the date that progression or death is documented (if one has occurred) or to the date of last follow-up (for those patients who have not progressed) up to 2 years
- Frequency, severity and relatedness of adverse events, graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 30 days post last day of treatment ] [ Designated as safety issue: Yes ]
- Pharmacodynamic, cytokine, primary/secondary resistance studies of ibrutinib, and baseline profiling of tumor cells [ Time Frame: Pre-dose on course 1 day 1 and 2 hours post-dose course 1 day 1; pre-dose day 2 and day 8 of course 1; pre-dose on day 1 of courses 2 and 3 and then every 3 months thereafter for 1 year ] [ Designated as safety issue: No ]
- Patient reported emotional distress and health related quality of life [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
- Decrease in immune suppression of CLL cells [ Time Frame: up to 3 months ] [ Designated as safety issue: No ]
- Effectiveness of ibrutinib bridging patients to allogeneic stem cell transplant and outcome of patients following this intervention [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Transplant is a positive clinical outcome, those who go to transplant prior to two years will be considered a treatment success and included in the numerator of this proportion.
|Study Start Date:||May 2012|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (ibrutinib)
Patients will be treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) and not experiencing any unacceptable toxicity. Subjects with disease progression will be removed from the study. Correlative laboratory samples, quality of life assessment, and immunologic data would be collected over time of 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.
Other Names:Other: Correlative laboratory samples
Blood samples will be collected and used for pharmacodynamic testing. Samples will be collected pre-dose on Cycle 1 Day 1 and 2 hours post-dose Cycle 1 Day 1, pre-dose on Day 2 and Day 8 of Cycle 1 and pre-dose on Day 1 of Cycles 2 and 3 and then every 3 cycles thereafter for 1 year (Cycle 15 Day 1). Samples will also be collected at the time of relapse and at any time when bone marrow biopsy is performed.
Other Name: laboratory biomarker anyalysisOther: quality of life assessment
During screening, sociodemographic information (e.g., age, race, marital status) and reports of recent (last year) stressful events will be obtained. The assessment will consist of measures of emotional distress, depressive symptoms, and quality of life. Quality of life measures will be administered during screening and on Days 1 (±3), 8 (±3),, 15 (±3),, 22 (±3), of Cycle 1, Day 1 (±3), of Cycle 2 and on day 1 (±7) of Cycles 3, 6, and then every 3 months thru month 24.
This is a clinical trial, a type of research study, involving treatment with an investigational (experimental) drug called PCI-32765 (Ibrutinib), a "kinase inhibitor". "Kinases" are proteins that are inside of cells and help them to live and grow. The specific kinase inhibited or blocked by this study drug is believed to help blood cancer cells grow and live. By inhibiting or "blocking" the activity of this kinase, it is possible that the study drug may be able to kill the cancer cells or stop them from growing. This study will involve treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or B-cell prolymphocytic leukemia (B-PLL) that has not responded to or has relapsed after standard treatment. This trial is studying how effective PCI-32765 is at treating CLL, SLL, or B-PLL and all the effects, good and/or bad, treatment with this drug has on patients and their cancers.
|Contact: Ohio State University Comprehensive Cancer Center||1-800-293-5066||Jamesline@osumc.edu|
|Contact: Kami Maddocks, MDfirstname.lastname@example.org|
|United States, Ohio|
|Ohio State University Medical Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Kami J. Maddocks, MD 614-293-3507 email@example.com|
|Principal Investigator: Kami J. Maddocks|
|Sub-Investigator: John Byrd, MD|
|Sub-Investigator: Joseph Flynn, DO|
|Sub-Investigator: Leslie Andritsos, MD|
|Sub-Investigator: Beth Christian, MD|
|Sub-Investigator: Samantha Jaglowski, MD|
|Sub-Investigator: Jennifer Woyach, MD|
|Sub-Investigator: Jeffrey A Jones, MD, MPH|
|Principal Investigator:||Kami Maddocks, MD||Ohio State University|