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

NCT01589302 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: OSU-11133NCI-2012-00560
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory/Relapsed Chronic Lymphocytic Leukemia

Keywords

Bruton's Tyrosine Kinase; CLL; SLL; B-PLL

Outcome Measures

Primary Outcomes (1)

• Determine the 2 Year Progression-free Survival (PFS) of Single Agent PCI-32765 in Patients With Relapsed and Refractory CLL.

  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.

  up to 2 years

Secondary Outcomes (15)

• Best Overall Response Rate Using the Revised International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Working Group Guidelines

  up to 2 years

• Number of Patients With 6 Month ORR of Single Agent Ibrutinib in Relapsed and Refractory CLL Patients

  Up to 6 months

• Percentage of Patients With Overall Survival (OS)

  2 years

• 2-year Kaplan-Meier Estimate of OS for Relapsed and Refractory CLL Patients Treated With Single Agent PCI-32765

  2 years

• Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

  Up to 2 years post treatment

Study Arms (1)

Treatment (ibrutinib)

EXPERIMENTAL

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; Other: Correlative laboratory samples; Other: quality of life assessment

Interventions

quality of life assessment OTHER

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.

Treatment (ibrutinib)

ibrutinib DRUG

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.

Also known as: Bruton's tyrosine kinase inhibitor PCI-32765, BTK inhibitor PCI-32765, PCI-32765

Treatment (ibrutinib)

Correlative laboratory samples OTHER

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.

Also known as: laboratory biomarker anyalysis

Treatment (ibrutinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 other Vitamin K antagonists or heparin products including low molecular weight heparin (LMWH)
• Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification
• 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

Sponsors & Collaborators

• Kami Maddocks, MD: lead

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (3)

• Arrato NA, Valentine TR, Byrd JC, Jones JA, Maddocks KJ, Woyach JA, Andersen BL. Illness representations and psychological outcomes in chronic lymphocytic leukaemia. Br J Health Psychol. 2022 May;27(2):553-570. doi: 10.1111/bjhp.12562. Epub 2021 Oct 4.

  PMID: 34608724 DERIVED

• Long M, Beckwith K, Do P, Mundy BL, Gordon A, Lehman AM, Maddocks KJ, Cheney C, Jones JA, Flynn JM, Andritsos LA, Awan F, Fraietta JA, June CH, Maus MV, Woyach JA, Caligiuri MA, Johnson AJ, Muthusamy N, Byrd JC. Ibrutinib treatment improves T cell number and function in CLL patients. J Clin Invest. 2017 Aug 1;127(8):3052-3064. doi: 10.1172/JCI89756. Epub 2017 Jul 17.

  PMID: 28714866 DERIVED

• Maddocks KJ, Ruppert AS, Lozanski G, Heerema NA, Zhao W, Abruzzo L, Lozanski A, Davis M, Gordon A, Smith LL, Mantel R, Jones JA, Flynn JM, Jaglowski SM, Andritsos LA, Awan F, Blum KA, Grever MR, Johnson AJ, Byrd JC, Woyach JA. Etiology of Ibrutinib Therapy Discontinuation and Outcomes in Patients With Chronic Lymphocytic Leukemia. JAMA Oncol. 2015 Apr;1(1):80-7. doi: 10.1001/jamaoncol.2014.218.

  PMID: 26182309 DERIVED

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Prolymphocytic; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Kami Maddocks, MD
• Organization: The Ohio State University Comprehensive Cancer Center

Kami.Maddocks@osumc.edu

614-293-3507

Study Officials

• Kami Maddocks, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 23, 2012
• First Posted: May 1, 2012
• Study Start: May 21, 2012
• Primary Completion: July 28, 2016
• Study Completion (Estimated): October 31, 2026
• Last Updated: April 13, 2026
• Results First Posted: May 21, 2019

Record last verified: 2026-03

Locations

US (1)