A Multicenter Phase 2 Study of Ibrutinib in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) With 17p Deletion

• ClinicalTrials.gov Identifier: NCT01744691
• Recruitment Status: Completed
• First Posted: December 7, 2012
• Results First Posted: June 9, 2015
• Last Update Posted: February 27, 2017
• Sponsor: Pharmacyclics LLC.
• Collaborator: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Pharmacyclics LLC.

Tracking Information

• First Submitted Date: December 3, 2012
• First Posted Date: December 7, 2012
• Results First Submitted Date: May 21, 2015
• Results First Posted Date: June 9, 2015
• Last Update Posted Date: February 27, 2017
• Study Start Date: January 2013
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 9, 2017)

Overall Response Rate [ Time Frame: The median time on study for all treated participants is 33.3 (range 0.5 - 40.1) months ]

The primary objective of this study is to evaluate the efficacy of ibrutinib in terms of ORR according to an Independent Review Committee (IRC). ORR based upon IRC assessment is the proportion of responders in the all treated population. Responders were subjects who achieved partial response (PR) or better, ie, complete response (CR), complete response with incomplete marrow recovery (CRi), nodule partial response (nPR) or PR, per IWCLL 2008 criteria with the clarification for treatment-related lymphocytosis.

• Original Primary Outcome Measures (submitted: December 6, 2012): Overall Response Rate [ Time Frame: 6 -12 months after last patient enrolled ]

Current Secondary Outcome Measures (submitted: May 21, 2015)

Number of Participants With Treatment Emergent Adverse Events (AEs) [ Time Frame: From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure ]

Number of participants who had experienced at least one treatment emergent AE

Original Secondary Outcome Measures (submitted: December 6, 2012)

• Duration of Response [ Time Frame: 18 months after last patient enrolled ]
• Safety Parameters: Number and type of adverse events [ Time Frame: 18 months after last patient enrolled ]

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: December 6, 2012)

• Progression-free survival [ Time Frame: 18 months after last patient enrolled ]
• Overall survival [ Time Frame: 18 months after last patient enrolled ]

Descriptive Information

• Brief Title: A Multicenter Phase 2 Study of Ibrutinib in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) With 17p Deletion
• Official Title: An Open-label, Single Arm, Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase Inhibitor PCI-32765 (Ibrutinib) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma With 17p Deletion (RESONATE™-17)
• Brief Summary: An Open-label, Single arm, Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase Inhibitor ibrutinib in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma with 17p Deletion
• Detailed Description: This is a multicenter, international, open-label, single arm, Phase 2 study designed to evaluate the efficacy and safety of ibrutinib in subjects with relapsed/refractory CLL or SLL with del 17p. All subjects will receive ibrutinib until disease progression or unacceptable toxicity occurs.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Chronic Lymphocytic Leukemia With 17p Deletion
• Small Lymphocytic Lymphoma With 17p Deletion

Intervention

Drug: Ibrutinib

All subjects will receive ibrutinib 420 mg (3 x 140-mg capsules) orally once daily.

Study Arms

Experimental: ibrutinib

All subjects will receive ibrutnib 420 mg (3 x 140-mg capsules) orally once daily.

Intervention: Drug: Ibrutinib

• Publications *: O'Brien S, Jones JA, Coutre SE, Mato AR, Hillmen P, Tam C, Osterborg A, Siddiqi T, Thirman MJ, Furman RR, Ilhan O, Keating MJ, Call TG, Brown JR, Stevens-Brogan M, Li Y, Clow F, James DF, Chu AD, Hallek M, Stilgenbauer S. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study. Lancet Oncol. 2016 Oct;17(10):1409-1418. doi: 10.1016/S1470-2045(16)30212-1. Epub 2016 Sep 13.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 21, 2015): 145
• Original Estimated Enrollment (submitted: December 6, 2012): 111
• Actual Study Completion Date: April 2016
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Documentation of del (17p13.1)
• Must have relapsed or refractory CLL/SLL after receiving at least 1 prior line of systemic therapy.
• Measurable nodal disease by computed tomography (CT)

Key Exclusion Criteria:

• History or current evidence of Richter's transformation or prolymphocytic leukemia
• Prior hematologic stem cell transplantation <6 months from study enrollment or any ongoing GVHD
• Prior exposure to ibrutinib

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, Germany, New Zealand, Sweden, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT01744691
• Other Study ID Numbers: PCYC-1117-CA; 2012-004476-19 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Pharmacyclics LLC.
• Original Responsible Party: Same as current
• Current Study Sponsor: Pharmacyclics LLC.
• Original Study Sponsor: Same as current
• Collaborators: Janssen Research & Development, LLC

Investigators

• Study Director: Alvina Chu, MD; Pharmacyclics LLC.

• PRS Account: Pharmacyclics LLC.
• Verification Date: January 2017