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

Sponsor
Pharmacyclics LLC. (Industry)
Overall Status
Completed
CT.gov ID
NCT01217749
Collaborator
Ohio State University (Other)
71
Enrollment
1
Location
3
Arms
41
Duration (Months)
1.7
Patients Per Site Per Month

Study Details

Study Description

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
Phase 1/Phase 2

Study Design

Study Type:
Interventional
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 :
Dec 1, 2010
Actual Primary Completion Date :
Jun 1, 2013
Actual Study Completion Date :
May 1, 2014

Arms and Interventions

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 Names:
  • ibrutinib

    • Drug: ofatumumab
    per package insert as an IV infusion
    Other Names:
  • 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 Names:
  • ibrutinib

    • Drug: ofatumumab
    per package insert as an IV infusion
    Other Names:
  • 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 Names:
  • ibrutinib

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Achieving Response [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 [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) [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 [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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

    1. 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

    2. 10% expression of CD20 on CLL/SLL cells

    3. ECOG performance status ≤ 2

    4. Life expectancy ≥ 12 weeks

    5. 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

    1. No history of prior exposure to ofatumumab

    2. Age ≥ 18 years

    3. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Ohio State University Columbus Ohio United States 43210

    Sponsors and Collaborators

    • Pharmacyclics LLC.
    • Ohio State University

    Investigators

    • Principal Investigator: Samantha Jaglowski, MD, Ohio State University

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pharmacyclics LLC.
    ClinicalTrials.gov Identifier:
    NCT01217749
    Other Study ID Numbers:
    • PCYC-1109-CA
    • PCI-32765
    First Posted:
    Oct 8, 2010
    Last Update Posted:
    Jun 25, 2015
    Last Verified:
    May 1, 2015
    Additional relevant MeSH terms:
    Lymphoma
    Leukemia
    Leukemia, Lymphoid
    Leukemia, Lymphocytic, Chronic, B-Cell
    Ofatumumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Group 1 Group 2 Group 3
    Arm/Group Description In Group 1, PCI-32765 420 mg PO was administered daily for 1 cycle (28 days) before the start of ofatumumab IV dosing In Group 2, PCI-32765 420 mg PO daily was initiated concomitantly with ofatumumab IV (PCI-32765 initiated on Day 2 of Cycle 1) In Group 3, two cycles of ofatumumab IV were administered prior to the start of PCI-32765 420 mg PO daily
    Period Title: Overall Study
    STARTED 27 20 24
    COMPLETED 24 17 22
    NOT COMPLETED 3 3 2

    Baseline Characteristics

    Arm/Group Title Group 1 Group 2 Group 3 Total
    Arm/Group Description In Group 1, PCI-32765 420 mg PO was administered daily for 1 cycle (28 days) before the start of ofatumumab IV dosing In Group 2, PCI-32765 420 mg PO daily was initiated concomitantly with ofatumumab IV (PCI-32765 initiated on Day 2 of Cycle 1) In Group 3, two cycles of ofatumumab IV were administered prior to the start of PCI-32765 420 mg PO daily Total of all reporting groups
    Overall Participants 27 20 24 71
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    13
    48.1%
    12
    60%
    15
    62.5%
    40
    56.3%
    >=65 years
    14
    51.9%
    8
    40%
    9
    37.5%
    31
    43.7%
    Sex: Female, Male (Count of Participants)
    Female
    8
    29.6%
    7
    35%
    7
    29.2%
    22
    31%
    Male
    19
    70.4%
    13
    65%
    17
    70.8%
    49
    69%
    Region of Enrollment (participants) [Number]
    United States
    27
    100%
    20
    100%
    24
    100%
    71
    100%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Achieving Response
    Description 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.
    Time Frame The median follow-up time on study for all treated participants is 12.5 (range 0.5-19.6) months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group 1 Group 2 Group 3
    Arm/Group Description In Group 1, PCI-32765 420 mg PO administered daily for 1 cycle (28 days) before the start of ofatumumab IV dosing In Group 2, PCI-32765 420 mg PO daily was initiated concomitantly with ofatumumab IV (PCI-32765 initiated on Day 2 of Cycle 1) In Group 3, two cycles of ofatumumab IV were administered prior to the start of PCI-32765 420 mg PO daily
    Measure Participants 27 20 24
    Number (95% Confidence Interval) [percentage of participants]
    92.6
    343%
    80.0
    400%
    70.8
    295%
    2. Secondary Outcome
    Title Number of Participants With Treatment Emergent Adverse Events (AEs)
    Description Number of participants who had experienced at least one treatment emergent AE
    Time Frame From first dose of study treatment to within 30 days of last dose or until study closure

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group 1 Group 2 Group 3
    Arm/Group Description In Group 1, PCI-32765 420 mg PO was administered daily for 1 cycle (28 days) before the start of ofatumumab IV dosing In Group 2, PCI-32765 420 mg PO daily was initiated concomitantly with ofatumumab IV (PCI-32765 initiated on Day 2 of Cycle 1) In Group 3, two cycles of ofatumumab IV were administered prior to the start of PCI-32765 420 mg PO daily
    Measure Participants 27 20 24
    Number [participants]
    27
    100%
    20
    100%
    24
    100%
    3. Secondary Outcome
    Title Progression Free Survival (PFS) at 12 Months
    Description 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
    Time Frame From first dose of study treatment until disease progression, death, or until 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group 1 Group 2 Group 3
    Arm/Group Description In Group 1, PCI-32765 420 mg PO daily was administered daily for 1 cycle (28 days) before the start of ofatumumab IV dosing In Group 2, PCI-32765 420 mg PO daily was initiated concomitantly with ofatumumab IV (PCI-32765 initiated on Day 2 of Cycle 1) In Group 3, two cycles of ofatumumab IV were administered prior to the start of PCI-32765 420 mg PO daily
    Measure Participants 27 20 24
    Mean (95% Confidence Interval) [percentage of event free participants]
    88.7
    328.5%
    85.0
    425%
    75.0
    312.5%
    4. Primary Outcome
    Title Safety During Dose-Limiting Toxicity (DLT) Observation Period
    Description Number of dose-limiting toxicities observed in the first 6 participants enrolled in treatment Groups 1 and 2
    Time Frame 56 days for Group 1 and 28 days for Group 2

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group 1 Group 2
    Arm/Group Description In Group 1, PCI-32765 420 mg PO was administered daily for 1 cycle (28 days) before the start of ofatumumab IV dosing In Group 2, PCI-32765 420 mg PO daily was initiated concomitantly with ofatumumab IV (PCI-32765 initiated on Day 2 of Cycle 1)
    Measure Participants 6 6
    Number [participants who experienced DLT]
    0
    0%
    0
    0%

    Adverse Events

    Time Frame From first dose of study treatment to within 30 days of last dose or until study closure
    Adverse Event Reporting Description
    Arm/Group Title Group 1 Group 2 Group 3
    Arm/Group Description In Group 1, PCI-32765 420 mg PO was administered daily for 1 cycle (28 days) before the start of ofatumumab IV dosing In Group 2, PCI-32765 420 mg PO daily was initiated concomitantly with ofatumumab IV (PCI-32765 initiated on Day 2 of Cycle 1) In Group 3, two cycles of ofatumumab IV were administered prior to the start of PCI-32765 420 mg PO daily
    All Cause Mortality
    Group 1 Group 2 Group 3
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Group 1 Group 2 Group 3
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 12/27 (44.4%) 9/20 (45%) 10/24 (41.7%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/27 (0%) 1/20 (5%) 1/24 (4.2%)
    Neutropenia 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Cardiac disorders
    Atrial fibrillation 2/27 (7.4%) 1/20 (5%) 1/24 (4.2%)
    Cardio-respiratory arrest 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Myocardial infarction 2/27 (7.4%) 0/20 (0%) 0/24 (0%)
    Gastrointestinal disorders
    Gastric ulcer 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    General disorders
    Pyrexia 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Infections and infestations
    Pneumonia 4/27 (14.8%) 3/20 (15%) 4/24 (16.7%)
    Cellulitis 1/27 (3.7%) 0/20 (0%) 2/24 (8.3%)
    Pneumonia fungal 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Sepsis 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Staphylococcal sepsis 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Urinary tract infection 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Atypical pneumonia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Gastroenteritis 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Pneumonia pseudomonas aeruginosa 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Viral upper respiratory tract infection 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Injury, poisoning and procedural complications
    Post procedural haemorrhage 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Subdural haematoma 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Metabolism and nutrition disorders
    Dehydration 2/27 (7.4%) 0/20 (0%) 0/24 (0%)
    Electrolyte imbalance 1/27 (3.7%) 1/20 (5%) 0/24 (0%)
    Fluid overload 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Gout 1/27 (3.7%) 1/20 (5%) 0/24 (0%)
    Hyponatraemia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Chronic lymphocytic leukaemia 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Renal cell carcinoma 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Richter's syndrome 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Nervous system disorders
    Ischaemic stroke 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    VIIth nerve paralysis 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Renal and urinary disorders
    Urinary retention 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/27 (0%) 1/20 (5%) 2/24 (8.3%)
    Haemothorax 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Organising pneumonia 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Other (Not Including Serious) Adverse Events
    Group 1 Group 2 Group 3
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 27/27 (100%) 20/20 (100%) 24/24 (100%)
    Blood and lymphatic system disorders
    Neutropenia 4/27 (14.8%) 5/20 (25%) 3/24 (12.5%)
    Anaemia 7/27 (25.9%) 2/20 (10%) 2/24 (8.3%)
    Increased tendency to bruise 10/27 (37%) 5/20 (25%) 2/24 (8.3%)
    Thrombocytopenia 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Lymph node pain 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Cardiac disorders
    Atrial fibrillation 0/27 (0%) 1/20 (5%) 2/24 (8.3%)
    Left ventricular dysfunction 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Palpitations 3/27 (11.1%) 1/20 (5%) 0/24 (0%)
    Ear and labyrinth disorders
    Ear pain 2/27 (7.4%) 0/20 (0%) 2/24 (8.3%)
    Deafness 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Hearing impaired 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Haematotympanum 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Motion sickness 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Tinnitus 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Eye disorders
    Conjunctival haemorrhage 0/27 (0%) 1/20 (5%) 3/24 (12.5%)
    Eye haemorrhage 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Eye pain 1/27 (3.7%) 1/20 (5%) 1/24 (4.2%)
    Vision blurred 0/27 (0%) 3/20 (15%) 1/24 (4.2%)
    Cataract 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Conjunctivitis 4/27 (14.8%) 0/20 (0%) 0/24 (0%)
    Intraocular haematoma 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Iridocyclitis 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Iris adhesions 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Ocular hyperaemia 1/27 (3.7%) 1/20 (5%) 0/24 (0%)
    Photophobia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Retinal haemorrhage 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Vitreous floaters 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Gastrointestinal disorders
    Diarrhoea 18/27 (66.7%) 16/20 (80%) 16/24 (66.7%)
    Stomatitis 11/27 (40.7%) 9/20 (45%) 7/24 (29.2%)
    Nausea 5/27 (18.5%) 6/20 (30%) 6/24 (25%)
    Abdominal distension 2/27 (7.4%) 1/20 (5%) 2/24 (8.3%)
    Abdominal pain 3/27 (11.1%) 1/20 (5%) 2/24 (8.3%)
    Dry mouth 3/27 (11.1%) 2/20 (10%) 2/24 (8.3%)
    Dyspepsia 5/27 (18.5%) 4/20 (20%) 2/24 (8.3%)
    Oral pain 0/27 (0%) 0/20 (0%) 2/24 (8.3%)
    Abdominal pain upper 2/27 (7.4%) 1/20 (5%) 1/24 (4.2%)
    Cheilitis 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Colitis 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Gastrooesophageal reflux disease 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Glossodynia 2/27 (7.4%) 0/20 (0%) 1/24 (4.2%)
    Oral mucosal blistering 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Paraesthesia oral 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Toothache 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Abdominal discomfort 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Abdominal hernia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Ascites 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Constipation 4/27 (14.8%) 1/20 (5%) 0/24 (0%)
    Dysphagia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Eructation 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Flatulence 3/27 (11.1%) 0/20 (0%) 0/24 (0%)
    Gastrointestinal motility disorder 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Gingival pain 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Haematemesis 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Haemorrhoidal haemorrhage 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Inguinal hernia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Oesophageal varices haemorrhage 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Swollen tongue 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Tongue blistering 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Tongue discolouration 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Tongue disorder 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Vomiting 4/27 (14.8%) 3/20 (15%) 0/24 (0%)
    General disorders
    Oedema peripheral 7/27 (25.9%) 2/20 (10%) 4/24 (16.7%)
    Chills 2/27 (7.4%) 0/20 (0%) 3/24 (12.5%)
    Pain 1/27 (3.7%) 0/20 (0%) 2/24 (8.3%)
    Chest discomfort 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Chest pain 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Fatigue 13/27 (48.1%) 1/20 (5%) 1/24 (4.2%)
    Localised oedema 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Asthenia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Axillary pain 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Catheter site pain 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Catheter site rash 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Injection site bruising 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Irritability 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Pyrexia 1/27 (3.7%) 1/20 (5%) 0/24 (0%)
    Temperature intolerance 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Hepatobiliary disorders
    Liver disorder 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Portal hypertension 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Immune system disorders
    Sarcoidosis 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Infections and infestations
    Upper respiratory tract infection 7/27 (25.9%) 8/20 (40%) 5/24 (20.8%)
    Sinusitis 6/27 (22.2%) 2/20 (10%) 3/24 (12.5%)
    Urinary tract infection 5/27 (18.5%) 2/20 (10%) 3/24 (12.5%)
    Bronchitis 2/27 (7.4%) 1/20 (5%) 1/24 (4.2%)
    Cellulitis 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Ear infection 1/27 (3.7%) 1/20 (5%) 1/24 (4.2%)
    Infection 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Nasal abscess 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Nasopharyngitis 0/27 (0%) 1/20 (5%) 1/24 (4.2%)
    Oral herpes 0/27 (0%) 2/20 (10%) 1/24 (4.2%)
    Pneumonia fungal 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Eye infection 1/27 (3.7%) 2/20 (10%) 0/24 (0%)
    Eye infection toxoplasmal 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Folliculitis 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Fungal skin infection 2/27 (7.4%) 1/20 (5%) 0/24 (0%)
    Furuncle 1/27 (3.7%) 1/20 (5%) 0/24 (0%)
    Gastroenteritis viral 4/27 (14.8%) 1/20 (5%) 0/24 (0%)
    Herpes simplex 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Herpes zoster 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Infected bites 1/27 (3.7%) 1/20 (5%) 0/24 (0%)
    Lower respiratory tract infection 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Onychomycosis 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Otitis media 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Pneumonia 6/27 (22.2%) 3/20 (15%) 0/24 (0%)
    Rash pustular 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Skin infection 2/27 (7.4%) 0/20 (0%) 0/24 (0%)
    Staphylococcal bacteraemia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Tinea infection 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Tinea pedis 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Viral upper respiratory tract infection 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Injury, poisoning and procedural complications
    Infusion related reaction 9/27 (33.3%) 14/20 (70%) 9/24 (37.5%)
    Contusion 9/27 (33.3%) 8/20 (40%) 3/24 (12.5%)
    Arthropod bite 2/27 (7.4%) 5/20 (25%) 1/24 (4.2%)
    Fall 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Foot fracture 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Meniscus injury 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Procedural pain 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Thermal burn 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Animal bite 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Jaw fracture 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Laceration 3/27 (11.1%) 0/20 (0%) 0/24 (0%)
    Periorbital contusion 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Post procedural haematoma 2/27 (7.4%) 0/20 (0%) 0/24 (0%)
    Skin wound 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Wound 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Wound haemorrhage 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Wrist fracture 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Investigations
    Neutrophil count decreased 1/27 (3.7%) 2/20 (10%) 1/24 (4.2%)
    Activated partial thromboplastin time prolonged 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Blood creatinine increased 1/27 (3.7%) 1/20 (5%) 0/24 (0%)
    Grip strength decreased 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    International normalised ratio increased 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Weight decreased 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Weight increased 2/27 (7.4%) 0/20 (0%) 0/24 (0%)
    Metabolism and nutrition disorders
    Hyperglycaemia 1/27 (3.7%) 0/20 (0%) 2/24 (8.3%)
    Hypokalaemia 5/27 (18.5%) 2/20 (10%) 2/24 (8.3%)
    Decreased appetite 4/27 (14.8%) 2/20 (10%) 1/24 (4.2%)
    Hypocalcaemia 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Hypoglycaemia 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Dehydration 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Gout 2/27 (7.4%) 1/20 (5%) 0/24 (0%)
    Hyperkalaemia 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Hypernatraemia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Hyperuricaemia 4/27 (14.8%) 2/20 (10%) 0/24 (0%)
    Hypervolaemia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Hyponatraemia 3/27 (11.1%) 0/20 (0%) 0/24 (0%)
    Hypophosphataemia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 5/27 (18.5%) 2/20 (10%) 5/24 (20.8%)
    Pain in extremity 6/27 (22.2%) 3/20 (15%) 3/24 (12.5%)
    Muscle spasms 10/27 (37%) 4/20 (20%) 2/24 (8.3%)
    Musculoskeletal chest pain 0/27 (0%) 2/20 (10%) 2/24 (8.3%)
    Myalgia 2/27 (7.4%) 1/20 (5%) 2/24 (8.3%)
    Back pain 3/27 (11.1%) 1/20 (5%) 1/24 (4.2%)
    Musculoskeletal pain 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Arthritis 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Bone pain 2/27 (7.4%) 1/20 (5%) 0/24 (0%)
    Exostosis 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Joint swelling 1/27 (3.7%) 1/20 (5%) 0/24 (0%)
    Muscular weakness 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Neck pain 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Osteoarthritis 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Pain in jaw 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Plantar fasciitis 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Tendon pain 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Tendonitis 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/27 (0%) 1/20 (5%) 1/24 (4.2%)
    Lipoma 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Squamous cell carcinoma 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Malignant melanoma 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Meningioma benign 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Squamous cell carcinoma of skin 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Uterine leiomyoma 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Nervous system disorders
    Peripheral sensory neuropathy 11/27 (40.7%) 8/20 (40%) 12/24 (50%)
    Headache 2/27 (7.4%) 1/20 (5%) 3/24 (12.5%)
    Dizziness 4/27 (14.8%) 4/20 (20%) 1/24 (4.2%)
    Dizziness postural 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Dysgeusia 4/27 (14.8%) 1/20 (5%) 1/24 (4.2%)
    Hypoaesthesia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Neuropathy peripheral 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Peripheral motor neuropathy 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Psychiatric disorders
    Anxiety 2/27 (7.4%) 0/20 (0%) 1/24 (4.2%)
    Confusional state 4/27 (14.8%) 0/20 (0%) 0/24 (0%)
    Insomnia 5/27 (18.5%) 6/20 (30%) 0/24 (0%)
    Renal and urinary disorders
    Dysuria 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Pollakiuria 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Renal mass 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Chromaturia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Renal failure 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Renal failure acute 1/27 (3.7%) 1/20 (5%) 0/24 (0%)
    Urinary retention 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Reproductive system and breast disorders
    Erectile dysfunction 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Vaginal haemorrhage 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Vulvovaginal pruritus 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Respiratory, thoracic and mediastinal disorders
    Sinus congestion 0/27 (0%) 2/20 (10%) 4/24 (16.7%)
    Oropharyngeal pain 3/27 (11.1%) 0/20 (0%) 3/24 (12.5%)
    Epistaxis 3/27 (11.1%) 3/20 (15%) 2/24 (8.3%)
    Dyspnoea 3/27 (11.1%) 0/20 (0%) 1/24 (4.2%)
    Dyspnoea exertional 3/27 (11.1%) 0/20 (0%) 1/24 (4.2%)
    Haemoptysis 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Pleural effusion 2/27 (7.4%) 1/20 (5%) 1/24 (4.2%)
    Throat irritation 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Upper-airway cough syndrome 2/27 (7.4%) 0/20 (0%) 1/24 (4.2%)
    Vocal cord cyst 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Wheezing 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Chronic obstructive pulmonary disease 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Cough 1/27 (3.7%) 1/20 (5%) 0/24 (0%)
    Dry throat 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Dysphonia 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Hiccups 2/27 (7.4%) 0/20 (0%) 0/24 (0%)
    Hypoxia 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Paranasal sinus hypersecretion 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Pneumothorax 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Productive cough 3/27 (11.1%) 3/20 (15%) 0/24 (0%)
    Stridor 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Skin and subcutaneous tissue disorders
    Petechiae 6/27 (22.2%) 5/20 (25%) 6/24 (25%)
    Rash 3/27 (11.1%) 2/20 (10%) 5/24 (20.8%)
    Alopecia 0/27 (0%) 2/20 (10%) 3/24 (12.5%)
    Ecchymosis 1/27 (3.7%) 0/20 (0%) 2/24 (8.3%)
    Eczema 0/27 (0%) 0/20 (0%) 2/24 (8.3%)
    Rash erythematous 0/27 (0%) 1/20 (5%) 2/24 (8.3%)
    Actinic keratosis 1/27 (3.7%) 0/20 (0%) 1/24 (4.2%)
    Blister 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Dermatitis contact 1/27 (3.7%) 1/20 (5%) 1/24 (4.2%)
    Ingrowing nail 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Onychoclasis 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Pruritus 2/27 (7.4%) 0/20 (0%) 1/24 (4.2%)
    Rash pruritic 0/27 (0%) 1/20 (5%) 1/24 (4.2%)
    Blood blister 2/27 (7.4%) 0/20 (0%) 0/24 (0%)
    Decubitus ulcer 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Dermatitis bullous 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Drug eruption 2/27 (7.4%) 1/20 (5%) 0/24 (0%)
    Erythema 0/27 (0%) 2/20 (10%) 0/24 (0%)
    Erythema nodosum 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Hyperhidrosis 2/27 (7.4%) 0/20 (0%) 0/24 (0%)
    Leukocytoclastic vasculitis 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Rash macular 2/27 (7.4%) 2/20 (10%) 0/24 (0%)
    Rash maculo-papular 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Rash papular 1/27 (3.7%) 3/20 (15%) 0/24 (0%)
    Skin fissures 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Skin hyperpigmentation 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Skin lesion 3/27 (11.1%) 2/20 (10%) 0/24 (0%)
    Skin mass 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Skin ulcer 3/27 (11.1%) 0/20 (0%) 0/24 (0%)
    Urticaria 1/27 (3.7%) 0/20 (0%) 0/24 (0%)
    Vascular disorders
    Hypertension 5/27 (18.5%) 0/20 (0%) 2/24 (8.3%)
    Deep vein thrombosis 0/27 (0%) 0/20 (0%) 1/24 (4.2%)
    Flushing 4/27 (14.8%) 2/20 (10%) 1/24 (4.2%)
    Haematoma 0/27 (0%) 1/20 (5%) 0/24 (0%)
    Hypotension 2/27 (7.4%) 3/20 (15%) 0/24 (0%)
    Peripheral artery aneurysm 1/27 (3.7%) 0/20 (0%) 0/24 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Jutta K. Neuenburg
    Organization Pharmacyclics, Inc.
    Phone 877-877-3536
    Email medinfo@pcyc.com
    Responsible Party:
    Pharmacyclics LLC.
    ClinicalTrials.gov Identifier:
    NCT01217749
    Other Study ID Numbers:
    • PCYC-1109-CA
    • PCI-32765
    First Posted:
    Oct 8, 2010
    Last Update Posted:
    Jun 25, 2015
    Last Verified:
    May 1, 2015