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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.

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

Condition or disease Intervention/treatment Phase
B-cell Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Prolymphocyctic Leukemia Richter's Transformation Drug: PCI-32765 Drug: ofatumumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 71 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : December 2010
Actual Primary Completion Date : June 2013
Actual Study Completion Date : May 2014

Arm Intervention/treatment
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
420 mg PO daily
Other Name: ibrutinib

Drug: ofatumumab
per package insert as an IV infusion
Other Name: Arzerra

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
420 mg PO daily
Other Name: ibrutinib

Drug: ofatumumab
per package insert as an IV infusion
Other Name: Arzerra

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
420 mg PO daily
Other Name: ibrutinib

Drug: ofatumumab
per package insert as an IV infusion
Other Name: Arzerra

Primary Outcome Measures :
  1. 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.

  2. 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

Secondary Outcome Measures :
  1. 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

  2. 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

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01217749

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United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Pharmacyclics LLC.
Ohio State University
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Principal Investigator: Samantha Jaglowski, MD Ohio State University
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):

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Responsible Party: Pharmacyclics LLC. Identifier: NCT01217749    
Other Study ID Numbers: PCYC-1109-CA
PCI-32765 ( Other Identifier: Pharmacyclics )
First Posted: October 8, 2010    Key Record Dates
Results First Posted: April 16, 2015
Last Update Posted: June 25, 2015
Last Verified: May 2015
Additional relevant MeSH terms:
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Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents