PCI-32765 (Ibrutinib) in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-cell Prolymphocytic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Ohio State University Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Kami Maddocks, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01589302
First received: April 23, 2012
Last updated: November 27, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Prolymphocytic Leukemia
Recurrent Small Lymphocytic Lymphoma
Refractory/Relapsed Chronic Lymphocytic Leukemia
Drug: ibrutinib
Other: Correlative laboratory samples
Other: quality of life assessment
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 78
Study Start Date: May 2012
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: ibrutinib
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:
  • Bruton's tyrosine kinase inhibitor PCI-32765
  • BTK inhibitor PCI-32765
  • PCI-32765
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 anyalysis
Other: 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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of relapsed/refractory CLL/SLL who require treatment and have failed at least one prior therapy.
  • Patients must have available results of interphase cytogenetics CLL fluorescent in situ hybridization (FISH) panel; the cytogenetic analysis must be done prior to starting therapy but after any recent therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy greater than 2 months
  • Bilirubin =< 1.5 X the institutional upper limit of normal unless due to Gilbert's disease or disease related to Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 X the institutional upper limit of normal unless disease related
  • Creatinine =< 1.5 X the institutional upper limit of normal unless disease related
  • Absolute neutrophil count (ANC) >= 0.75 X 10^9/L
  • Platelet count >= 30 X 10^9/L
  • Agree to use contraception during the study and for 30 days after the last dose of study drug if sexually active and able to bear children
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients with uncontrolled or active infection requiring antibiotic therapy; patients with controlled infections who are receiving extended antibiotics or prophylactic therapy are not excluded

Exclusion Criteria:

  • Patients who have had chemotherapy, radiotherapy or immunotherapy within 4 weeks prior to the first dose of study drug (corticosteroids for disease-related symptoms allowed but doses equivalent to > 20 mg prednisone orally per day require 1 week washout before study drug administration or steroid dose must be equal to =< 20 mg prednisone orally daily)
  • Patients who have not recovered from adverse events of >= grade 3 toxicity due to agents administered more than 4 weeks ago
  • Receiving any other investigational agents
  • Previously randomized to any PCI-32765 clinical trial
  • Known secondary malignancy that limits survival to less than two years
  • Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
  • Patients requiring anti-coagulation with warfarin or heparin products including low molecular weight heparin (LMWH)
  • Patients requiring treatment with a strong cytochrome P450 3A4/5 (CYP3A4/5) and/or cytochrome P450 2D6 (CYP2D6) inhibitor
  • Patients with a life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk
  • Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  • Active central nervous system (CNS) involvement by lymphoma
  • Pregnant or women who are breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01589302

Contacts
Contact: Ohio State University Comprehensive Cancer Center 1-800-293-5066 Jamesline@osumc.edu
Contact: Kami Maddocks, MD 614-293-3507 kami.maddocks@osumc.edu

Locations
United States, Ohio
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Kami J. Maddocks, MD    614-293-3507    kami.maddocks@osumc.edu   
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         
Sponsors and Collaborators
Kami Maddocks
Investigators
Principal Investigator: Kami Maddocks, MD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Kami Maddocks, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01589302     History of Changes
Other Study ID Numbers: OSU-11133, NCI-2012-00560
Study First Received: April 23, 2012
Last Updated: November 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:
Bruton's Tyrosine Kinase
CLL
SLL
B-PLL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Prolymphocytic
Lymphoma
Leukemia, Prolymphocytic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 20, 2014