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Efficacy and Safety Study of PCI-32765 Combine With Ofatumumab in CLL (PCYC-1109-CA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01217749
Recruitment Status : Completed
First Posted : October 8, 2010
Results First Posted : April 16, 2015
Last Update Posted : June 25, 2015
Ohio State University
Information provided by (Responsible Party):
Pharmacyclics LLC.

Tracking Information
First Submitted Date  ICMJE October 7, 2010
First Posted Date  ICMJE October 8, 2010
Results First Submitted Date  ICMJE April 2, 2015
Results First Posted Date  ICMJE April 16, 2015
Last Update Posted Date June 25, 2015
Study Start Date  ICMJE December 2010
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2015)
  • Percentage of Participants Achieving Response [ Time Frame: The median follow-up time on study for all treated participants is 12.5 (range 0.5-19.6) months ]
    The primary endpoint for the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR), CR with incomplete blood count recovery (Cri), or partial response (PR), according to the guidelines from the International Workshop on Chronic Lymphocytic Leukemia (IWCLL1) published in 2008 for CLL participants and International Working Group for non-Hodgkin's lymphoma (IWG NHL) 2007 criteria for SLL participants, with the modification that treatment-related lymphocytosis will not be considered progressive disease, as evaluated by the investigators. Assessment of disease is based on radiological exams, physical exam, hematological evaluations and, when appropriate, bone marrow results.
  • Safety During Dose-Limiting Toxicity (DLT) Observation Period [ Time Frame: 56 days for Group 1 and 28 days for Group 2 ]
    Number of dose-limiting toxicities observed in the first 6 participants enrolled in treatment Groups 1 and 2
Original Primary Outcome Measures  ICMJE
 (submitted: October 7, 2010)
Response and safety of PCI-32765 [ Time Frame: 1-3 cycles after last dose of study drug ]
Response rate as defined by recent guidelines in Chronic Lymphocytic Leukemia
Change History Complete list of historical versions of study NCT01217749 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2015)
  • Number of Participants With Treatment Emergent Adverse Events (AEs) [ Time Frame: From first dose of study treatment to within 30 days of last dose or until study closure ]
    Number of participants who had experienced at least one treatment emergent AE
  • Progression Free Survival (PFS) at 12 Months [ Time Frame: From first dose of study treatment until disease progression, death, or until 12 months ]
    Progressive disease for CLL (Hallek) is characterized by ≥1 of the following:
    • Appearance of any new lesion, eg lymph nodes (> 1.5 cm), de novo hepatomegaly or splenomegaly, or other organ infiltrates
    • Increase of ≥50%
      • in longest diameter of any previous site
      • in hepatomegaly or splenomegaly
      • in blood lymphocytes with ≥5x109/L B cells with enlarging lymph node, liver, or spleen
    Progressive disease for B cell lymphoma (Cheson) is characterized by any new lesion or increase by ≥ 50% of previously involved sites from nadir:
    • Appearance of a new lesion(s) >1.5 cm in any axis, ≥ 50% increase in the SPD of >1 node, or ≥50% increase in longest diameter of a previously identified node >1 cm in short axis
    • Lesions PET+ if FDG-avid lymphoma or PET+ before therapy
    • 50% increase from nadir in the SPD of any liver or spleen lesions
    • New or recurrent BM involvement
    • Increase of ≥50% in blood lymphocytes with ≥5x109/L B cells within enlarging lymph node, liver, or spleen
Original Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2010)
  • Pharmacokinetic/Pharmacodynamic assessments [ Time Frame: during 1-2 cycles ]
    Designed as safety issue Pharmacodynamics of PCI-32765 (ie, drug occupancy of Btk and effect on biologicial market 1/2) of PCI-32765.
  • Tumor Response [ Time Frame: at the end of Cycles 2,4 and 6 (28 days for each cycle) ]
    Overall response rate as defined by recent guidelines on CLL
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of PCI-32765 Combine With Ofatumumab in CLL
Official Title  ICMJE An Open-label, Phase 1b/2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, and Ofatumumab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Prolymphocytic Leukemia
Brief Summary The purpose of this study is to determine the efficacy and safety of a fixed-dose, daily regimen of orally administered PCI-32765 combined with ofatumumab in subjects with relapsed/refractory CLL/SLL and related diseases
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • B-cell Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Prolymphocyctic Leukemia
  • Richter's Transformation
Intervention  ICMJE
  • Drug: PCI-32765
    420 mg PO daily
    Other Name: ibrutinib
  • Drug: ofatumumab
    per package insert as an IV infusion
    Other Name: Arzerra
Study Arms  ICMJE
  • Experimental: Group 1
    In Group 1, PCI-32765 420 mg PO was administered daily for 1 cycle (28 days) before the start of ofatumumab IV dosing
    • Drug: PCI-32765
    • Drug: ofatumumab
  • Experimental: Group 2
    In Group 2, PCI-32765 420 mg PO daily was initiated concomitantly with ofatumumab IV (PCI-32765 initiated on Day 2 of Cycle 1)
    • Drug: PCI-32765
    • Drug: ofatumumab
  • Experimental: Group 3
    In Group 3, two cycles of ofatumumab IV were administered prior to the start of PCI-32765 420 mg PO daily
    • Drug: PCI-32765
    • Drug: ofatumumab
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 29, 2012)
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2010)
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subjects with histologically confirmed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), prolymphocytic leukemia (PLL), or Richter's transformation arising out of CLL/SLL as defined by WHO classification of hematopoietic neoplasms and satisfying ≥ 1 of the following conditions:

    • Progressive splenomegaly and/or lymphadenopathy identified by physical examination or radiographic studies
    • Anemia (<11 g/dL) or thrombocytopenia (<100,000/μL) due to bone marrow involvement
    • Presence of unintentional weight loss > 10% over the preceding 6 months
    • NCI CTCAE Grade 2 or 3 fatigue
    • Fevers > 100.5 degree or night sweats for > 2 weeks without evidence of infection
    • Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of < 6 months
    • Need for cytoreduction prior to stem cell transplant
  2. Subjects must have failed ≥ 2 prior therapies for CLL including a nucleoside analog or ≥ 2 prior therapies not including nucleoside analog if there is a contraindication to such therapy
  3. 10% expression of CD20 on CLL/SLL cells
  4. ECOG performance status ≤ 2
  5. Life expectancy ≥ 12 weeks
  6. Subjects must have organ and marrow function as defined below:

    • Absolute neutrophil count (ANC) ≥ 1000/µL in the absence of bone marrow involvement
    • Platelets ≥ 30,000/μL in the absence of bone marrow involvement
    • Total bilirubin ≤ 1.5 x institutional upper limit of normal unless due to Gilbert's disease
    • AST (SGOT) ≤ 2.5 x institutional upper limit of normal unless due to infiltration of the liver
    • Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min
  7. No history of prior exposure to ofatumumab
  8. Age ≥ 18 years
  9. Body weight ≥ 40 kg

Exclusion Criteria:

  1. 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
  2. Significant cardiovascular disease
  3. Any condition which could interfere with the absorption or metabolism of PCI-32765 including unable to swallow capsules, 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
  4. Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection
  5. Any anticancer immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 4 weeks before first dose of study drug. Corticosteroids for disease-related symptoms are allowed provided 1 week washout occurs
  6. Active central nervous system (CNS) involvement by lymphoma
  7. Major surgery within 4 weeks before first dose of study drug
  8. Lactating or pregnant
  9. Known moderate to severe chronic obstructive pulmonary disease (COPD)
  10. History of prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least 2 years or which will not limit survival to < 2 years
  11. History of Grade ≥ 2 toxicity continuing from prior anticancer therapy including radiation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01217749
Other Study ID Numbers  ICMJE PCYC-1109-CA
PCI-32765 ( Other Identifier: Pharmacyclics )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pharmacyclics LLC.
Study Sponsor  ICMJE Pharmacyclics LLC.
Collaborators  ICMJE Ohio State University
Investigators  ICMJE
Principal Investigator: Samantha Jaglowski, MD Ohio State University
PRS Account Pharmacyclics LLC.
Verification Date May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP