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Efficacy and Safety Study of Fostamatinib Tablets to Treat B-cell Lymphoma

Sponsor
Rigel Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00446095
Collaborator
(none)
81
Enrollment
11
Locations
1
Arm
42
Duration (Months)
7.4
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients: B-cell lymphoma, refractory, diffuse, nodular, mantle, other Phase I : Two groups of 6 patients, escalating dose tolerability- 28 days Phase II: Three groups of 16 patients (nodular, diffuse large cell, mantle cell plus others). Oral bid dosing with highest tolerable dose until toxicity, progression, or withdrawal

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

This multicenter, open-label study of fostamatinib will take place in two phases.

Phase I Two cohorts, of 6 patients each, will be sequentially assigned to receive 200 mg (Cohort 1) and 250 mg (Cohort 2) PO bid of R788. Patients will be enrolled at 250 mg bid in Cohort 2 only if < 1/6 patients in Cohort 1 experience dose-limiting toxicity (DLT) during the initial 28-day treatment period. If 2 or more patients in Cohort 1 experience DLT during the initial 28-day treatment period, patients in Cohort 2 will receive 150 mg PO bid.

Patients who do not experience DLT or disease progression may continue treatment at the assigned dose level until disease progression, toxicity or withdrawal. Patients who experience DLT may resume treatment at a lower dose level (dose will be decreased by 50 mg) when the toxicity grade has decreased to ≤ 1. Once all patients in Phase I have completed 28 days of treatment, the optimal dose of fostamatinib, based on safety and anti-tumor activity, will be determined.

Phase II 48 additional patients, 3 groups of 16 patients each, will receive fostamatinib at the optimal biologic dose PO bid until tumor progression, limiting toxicity or withdrawal. Group 1 will consist of patients with diffuse large B-cell lymphoma (DLBCL), Group 2 will consist of patients with follicular lymphoma, and Group 3 will consist of patients with mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphomas, small lymphocytic lymphomas (SLL), and chronic lymphocytic leukemia (CLL).

Study Design

Study Type:
Interventional
Actual Enrollment :
81 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Multi-Center, Open Label Trial of the Safety and Efficacy of Fostamatinib in Patients With Relapsed/Refractory B-Cell Lymphoma
Study Start Date :
Apr 1, 2007
Actual Primary Completion Date :
Apr 1, 2010
Actual Study Completion Date :
Oct 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: fostamatinib

Drug: fostamatinib
200 mg PO BID
Other Names:
  • R935788, R788, fostamatinib

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate as Assessed According to the"Revised Response Criteria for Malignant Lymphoma" (Cheson 2007). [Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response . (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days)]

      Proportion of patients with Complete Response (CR) or Partial Response (PR). Revised Response Criteria for Malignant Lymphoma categorises the response of the treatment of a patient's tumour to; CR: the disappearance of all evidence of disease; PR: ≥ 50% decrease in the sum of the perpendicular diameters (SPD) of the six largest dominant nodes plus no increase in the size of other nodes and no new sites of disease; Stable Disease (SD): less than a PR but not progressive disease; Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir. Primary efficacy is based on Phase II patients only.

    2. Clinical Benefit Rate as Assessed According to the "Revised Response Criteria for Malignant Lymphoma" (Cheson 2007). [Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days)]

      Proportion of patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD)

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) [Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days)]

      PFS: Time from date of first study drug administration to the date of progressive disease as assessed according to the "Revised Response Criteria for Malignant Lymphoma"(Cheson 2007) or the date of death due to any cause, whichever occurred first.

    2. Overall Survival (OS) [Overall survival is measured from the time of first administration of study drug to death. (Maximum duration of treatment 511days, Maximum duration of follow-up 812 Days)]

      OS: Time from date of first study drug administration to the date of death.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Patients must be > 18 years old.

    2. Patients must be willing and able to give written informed consent by signing an IRB-approved Informed Consent Form prior to admission to this study and must fully understand the requirements of the study and be willing to comply with all study visits and assessments.

    3. Patients with relapsed/refractory B-cell malignancy, (DLBCL, follicular lymphoma, mantle cell lymphoma, MALT lymphoma, marginal zone lymphoma, CLL or SLL), who have failed at least one prior treatment regimen and for whom no standard therapy exists; patients who are intolerant of standard therapy or who are not candidates for available standard therapy may also be included.

    4. Patients must have measurable disease.

    5. Patients may be male or female. Men, if sexually active, must agree to use at least one medically acceptable form of birth control for the duration of the study and for 30 days thereafter. Sexually active women of childbearing potential must have a negative serum pregnancy test, and agree to use two independent methods of birth control for the duration of the study and for 30 days thereafter.

    Exclusion Criteria:

    1. Patients with T-cell lymphoma or primary CNS lymphoma

    2. Patients with a history of malignancy other than lymphoma, except basal cell carcinoma of the skin and in situ cervical carcinoma, if < 2 years since curative treatment

    3. Chemotherapy within 4 weeks of Day 1 of treatment (6 weeks for mitomycin C and nitrosoureas)

    4. Antibody therapy or lymphoma vaccine therapy within 6 weeks of Day 1

    5. Radiotherapy within 2 weeks of Day 1, 4 weeks if to marrow-bearing sites (sternum, pelvis)

    6. Any other investigational therapy within 4 weeks of Day 1

    7. Significant gastrointestinal disease (Crohn's or ulcerative colitis) or major gastric or small bowel surgery

    8. Difficulty swallowing or malabsorption

    9. Patients with bone marrow impairment: Hgb < 9.0 g/dL; ANC < 1500/μL; platelets < 75,000/μL

    10. Patients with impairment of renal function: creatinine > 2.0 g/dL

    11. Patients with abnormal liver function: AST/ALT > 3x ULN (up to 5x ULN with liver involvement); bilirubin > 1.5 mg/dL

    12. Patients who have been treated with a CYP3A4 inducer/inhibitor within 1 week prior to Day 1 or who are expected to require treatment with CYP3A4 inducer/inhibitor during the course of the study (Appendix IV)

    13. Patients with Karnofsky performance status < 60% (Appendix I)

    14. Patients whose life expectancy is < 3 months

    15. Patients who are known to be HIV positive

    16. Patients who have a history of any other significant medical or physical condition that might impair the patient's well being or preclude full participation in the study

    17. Pregnant or nursing females

    18. Patients receiving systemic or chronic inhaled steroids, with the exception of intermittent dexamethasone for the treatment of emesis or intermittent steroid inhalers for exacerbations of asthma

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Los Angeles California United States 90095
    2 Research Site Stanford California United States 94305
    3 Research Site Atlanta Georgia United States 30322
    4 Research Site Chicago Illinois United States 60612
    5 Research Site Indianapolis Indiana United States 46202
    6 Research Site Boston Massachusetts United States 02115
    7 Research Site Rochester Minnesota United States 59905
    8 Research Site Omaha Nebraska United States 68198
    9 Research Site New York New York United States 10065
    10 Research Site Rochester New York United States 14642
    11 Research Site Cleveland Ohio United States 44195

    Sponsors and Collaborators

    • Rigel Pharmaceuticals

    Investigators

    • Study Director: Jeffrey Skolnik, M.D., AstraZeneca

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Rigel Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00446095
    Other Study ID Numbers:
    • D4300C00023
    • C-935788-009
    First Posted:
    Mar 12, 2007
    Last Update Posted:
    Sep 19, 2016
    Last Verified:
    Aug 1, 2016
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Rigel Pharmaceuticals
    DLCL
    Nodular lymphoma
    Mantle cell lymphoma
    Syk kinase
    Additional relevant MeSH terms:
    Lymphoma

    Study Results

    Participant Flow

    Recruitment Details A total of 81 patients with lymphoid malignancy were enrolled from 22 March 2007 until 31 January 2008, of which 13 were in Phase I and 68 in Phase II. This study was conducted by 11 investigators at 11 sites in U.S. Primary efficacy analysis was based on Phase II patients so only results from Phase II are posted.
    Pre-assignment Detail There was screening period of up to 21 days, after which if all inclusion/exclusion criteria were met, patients were dosed with fostamatinib treatment for a treatment period of 8 weeks. Patients could then continue treatment until disease progression, toxicity or withdrawal from the study
    Arm/Group Title Phase II: DLBCL Phase II: 250mg R788 BID Phase II: Other Lymphomas Phase I: 200mg R788 BID Phase I: 250mg R788 BID
    Arm/Group Description Patients with diffuse large B-cell lymphoma (DLBCL) in Phase II Patients who received 250mg R788 orally twice daily (PO BID) in Phase II Patients with mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphomas, small lymphocytic lymphomas and chronic lymphocytic leukemia (SLL/CLL) in Phase II Patients who received 200mg R788 orally twice daily (PO BID) in Phase I Patients who received 250mg R788 orally twice daily (PO BID) in Phase I
    Period Title: Phase II (8 Weeks)
    STARTED 23 21 24 0 0
    COMPLETED 11 18 21 0 0
    NOT COMPLETED 12 3 3 0 0
    Period Title: Phase II (8 Weeks)
    STARTED 0 0 0 6 7
    COMPLETED 0 0 0 5 4
    NOT COMPLETED 0 0 0 1 3

    Baseline Characteristics

    Arm/Group Title Phase II: DLBCL Phase II: 250mg R788 BID Phase II: Other Lymphomas Phase I: 200mg R788 BID Phase I: 250mg R788 BID Total
    Arm/Group Description Patients with diffuse large B-cell lymphoma (DLBCL) in Phase II Patients who received 250mg R788 orally twice daily (PO BID) in Phase II Patients with mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphomas, small lymphocytic lymphomas and chronic lymphocytic leukemia (SLL/CLL) in Phase II Patients who received 200mg R788 orally twice daily (PO BID) in Phase I Patients who received 250mg R788 orally twice daily (PO BID) in Phase I Total of all reporting groups
    Overall Participants 23 21 24 6 7 81
    Age (Years) [Mean (Full Range) ]
    Mean (Full Range) [Years]
    63.0
    (63)
    59.0
    (59)
    62.0
    (62)
    78.5
    61
    61.5
    (61.5)
    Sex: Female, Male (Count of Participants)
    Female
    5
    21.7%
    8
    38.1%
    7
    29.2%
    4
    66.7%
    5
    71.4%
    29
    35.8%
    Male
    18
    78.3%
    13
    61.9%
    17
    70.8%
    2
    33.3%
    2
    28.6%
    52
    64.2%
    Race/Ethnicity, Customized (Number) [Number]
    Caucasian
    20
    87%
    19
    90.5%
    21
    87.5%
    6
    100%
    5
    71.4%
    71
    87.7%
    Black/African American
    2
    8.7%
    0
    0%
    3
    12.5%
    0
    0%
    1
    14.3%
    6
    7.4%
    Asian
    0
    0%
    2
    9.5%
    0
    0%
    0
    0%
    1
    14.3%
    3
    3.7%
    Other: Russian
    1
    4.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.2%

    Outcome Measures

    1. Primary Outcome
    Title Overall Response Rate as Assessed According to the"Revised Response Criteria for Malignant Lymphoma" (Cheson 2007).
    Description Proportion of patients with Complete Response (CR) or Partial Response (PR). Revised Response Criteria for Malignant Lymphoma categorises the response of the treatment of a patient's tumour to; CR: the disappearance of all evidence of disease; PR: ≥ 50% decrease in the sum of the perpendicular diameters (SPD) of the six largest dominant nodes plus no increase in the size of other nodes and no new sites of disease; Stable Disease (SD): less than a PR but not progressive disease; Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir. Primary efficacy is based on Phase II patients only.
    Time Frame Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response . (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days)

    Outcome Measure Data

    Analysis Population Description
    Intention to treat (ITT) population is defined as all patients who received at least one dose of fostamatinib.
    Arm/Group Title Phase II: DLBCL Phase II: 250mg R788 BID Phase II: Other Lymphomas Phase 1: 200mg and 250mg R788 BID
    Arm/Group Description Patients with diffuse large B-cell lymphoma (DLBCL) in Phase II Patients who received 250mg R788 orally twice daily (PO BID) in Phase II Patients with mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphomas, small lymphocytic lymphomas and chronic lymphocytic leukemia (SLL/CLL) in Phase II Patients who received 200mg or 250mg R788 orally twice daily (PO BID) in Phase I
    Measure Participants 23 21 24 13
    Number [Participants]
    5
    21.7%
    2
    9.5%
    7
    29.2%
    1
    16.7%
    2. Primary Outcome
    Title Clinical Benefit Rate as Assessed According to the "Revised Response Criteria for Malignant Lymphoma" (Cheson 2007).
    Description Proportion of patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD)
    Time Frame Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days)

    Outcome Measure Data

    Analysis Population Description
    Intention to treat (ITT) population is defined as all patients who received at least one dose of fostamatinib.
    Arm/Group Title Phase II: DLBCL Phase II: 250mg R788 BID Phase II: Other Lymphomas Phase 1: 200mg and 250mg R788 BID
    Arm/Group Description Patients with diffuse large B-cell lymphoma (DLBCL) in Phase II Patients who received 250mg R788 orally twice daily (PO BID) in Phase II Patients with mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphomas, small lymphocytic lymphomas and chronic lymphocytic leukemia (SLL/CLL) in Phase II Patients who received 200mg or 250mg R788 orally twice daily (PO BID) in Phase I
    Measure Participants 23 21 24 13
    Number [Participants]
    9
    39.1%
    13
    61.9%
    14
    58.3%
    9
    150%
    3. Secondary Outcome
    Title Progression Free Survival (PFS)
    Description PFS: Time from date of first study drug administration to the date of progressive disease as assessed according to the "Revised Response Criteria for Malignant Lymphoma"(Cheson 2007) or the date of death due to any cause, whichever occurred first.
    Time Frame Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days)

    Outcome Measure Data

    Analysis Population Description
    Phase II only as was not collected in Phase I. Intention to treat (ITT) population is defined as all patients who received at least one dose of fostamatinib.
    Arm/Group Title Phase II: DLBCL Phase II: 250mg R788 BID Phase II: Other Lymphomas
    Arm/Group Description Patients with diffuse large B-cell lymphoma (DLBCL) in Phase II Patients who received 250mg R788 orally twice daily (PO BID) in Phase II Patients with mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphomas, small lymphocytic lymphomas and chronic lymphocytic leukemia (SLL/CLL) in Phase II
    Measure Participants 23 21 24
    Median (95% Confidence Interval) [Days]
    83.0
    141.0
    126.0
    4. Secondary Outcome
    Title Overall Survival (OS)
    Description OS: Time from date of first study drug administration to the date of death.
    Time Frame Overall survival is measured from the time of first administration of study drug to death. (Maximum duration of treatment 511days, Maximum duration of follow-up 812 Days)

    Outcome Measure Data

    Analysis Population Description
    Phase II only as was not collected in Phase I. Intention to treat (ITT) population is defined as all patients who received at least one dose of fostamatinib.
    Arm/Group Title Phase II: DLBCL Phase II: 250mg R788 BID Phase II: Other Lymphomas
    Arm/Group Description Patients with diffuse large B-cell lymphoma (DLBCL) in Phase II Patients who received 250mg R788 orally twice daily (PO BID) in Phase II Patients with mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphomas, small lymphocytic lymphomas and chronic lymphocytic leukemia (SLL/CLL) in Phase II
    Measure Participants 23 21 24
    Median (95% Confidence Interval) [Days]
    166.0
    NA
    NA

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Phase II: DLBCL Phase II: 250mg R788 BID Phase II: Other Lymphomas Phase I: 200mg R788 BID Phase I: 250mg R788 BID
    Arm/Group Description Patients with diffuse large B-cell lymphoma (DLBCL) in Phase II Patients who received 250mg R788 orally twice daily (PO BID) in Phase II Patients with mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphomas, small lymphocytic lymphomas and chronic lymphocytic leukemia (SLL/CLL) in Phase II Patients who received 200mg R788 orally twice daily (PO BID) in Phase I Patients who received 250mg R788 orally twice daily (PO BID) in Phase I
    All Cause Mortality
    Phase II: DLBCL Phase II: 250mg R788 BID Phase II: Other Lymphomas Phase I: 200mg R788 BID Phase I: 250mg R788 BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Phase II: DLBCL Phase II: 250mg R788 BID Phase II: Other Lymphomas Phase I: 200mg R788 BID Phase I: 250mg R788 BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/23 (60.9%) 7/21 (33.3%) 10/24 (41.7%) 6/6 (100%) 3/7 (42.9%)
    Blood and lymphatic system disorders
    Febrile Neutropenia 1/23 (4.3%) 1/21 (4.8%) 3/24 (12.5%) 0/6 (0%) 1/7 (14.3%)
    Pancytopenia 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Neutropenia 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Cardiac disorders
    Cardio-Respiratory Arrest 2/23 (8.7%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Cardiac Arrest 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Myocardial Ischaemia 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Cardiac failure 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Gastrointestinal disorders
    Abdominal Pain 2/23 (8.7%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Abdominal Pain Upper 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Ascites 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Diarrhoea 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Duodenal obstruction 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    General disorders
    Pyrexia 1/23 (4.3%) 0/21 (0%) 2/24 (8.3%) 1/6 (16.7%) 0/7 (0%)
    Chest Pain 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Infections and infestations
    Pneumonia 1/23 (4.3%) 1/21 (4.8%) 2/24 (8.3%) 2/6 (33.3%) 1/7 (14.3%)
    Cellulitis 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Gastroenteritis Viral 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Lung Infection Pseudomonal 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Pneumococcal Sepsis 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Sepsis 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 2/6 (33.3%) 0/7 (0%)
    Staphylococcal Infection 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Urinary Tract Infection 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 2/6 (33.3%) 0/7 (0%)
    Klebsiella bacteraemia 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Musculoskeletal and connective tissue disorders
    Pathological Fracture 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Tumour necrosis 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Nervous system disorders
    Lethargy 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Spinal Cord Compression 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Syncope 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Multifocal motor neuropathy 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Psychiatric disorders
    Mental Status Changes 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Renal and urinary disorders
    Renal Failure 0/23 (0%) 1/21 (4.8%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Renal Failure Acute 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Distress Syndrome 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Dyspnoea Exacerbated 1/23 (4.3%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Hypoxia 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Dyspnoea 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Vascular disorders
    Superior Vena Caval Occlusion 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Other (Not Including Serious) Adverse Events
    Phase II: DLBCL Phase II: 250mg R788 BID Phase II: Other Lymphomas Phase I: 200mg R788 BID Phase I: 250mg R788 BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 22/23 (95.7%) 21/21 (100%) 24/24 (100%) 6/6 (100%) 6/7 (85.7%)
    Blood and lymphatic system disorders
    Anaemia 5/23 (21.7%) 7/21 (33.3%) 9/24 (37.5%) 4/6 (66.7%) 2/7 (28.6%)
    Thrombocytopenia 7/23 (30.4%) 5/21 (23.8%) 8/24 (33.3%) 4/6 (66.7%) 1/7 (14.3%)
    Leukopenia 1/23 (4.3%) 7/21 (33.3%) 2/24 (8.3%) 4/6 (66.7%) 1/7 (14.3%)
    Neutropenia 7/23 (30.4%) 9/21 (42.9%) 11/24 (45.8%) 4/6 (66.7%) 2/7 (28.6%)
    Febrile neutropenia 1/23 (4.3%) 1/21 (4.8%) 3/24 (12.5%) 0/6 (0%) 1/7 (14.3%)
    Bone marrow failure 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Cardiac disorders
    Tachycardia 3/23 (13%) 0/21 (0%) 2/24 (8.3%) 1/6 (16.7%) 1/7 (14.3%)
    Atrial fibrillation 0/23 (0%) 1/21 (4.8%) 1/24 (4.2%) 1/6 (16.7%) 0/7 (0%)
    Cardiac failure congestive 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 2/6 (33.3%) 0/7 (0%)
    Cardiac failure 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 1/6 (16.7%) 0/7 (0%)
    Myocardial ischaemia 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 1/7 (14.3%)
    Palpitations 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Arrhythmia 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Intracardiac thrombus 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Ventricular tachycardia 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Ear and labyrinth disorders
    Tinnitus 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Eye disorders
    Conjunctival Haemorrhage 0/23 (0%) 0/21 (0%) 2/24 (8.3%) 0/6 (0%) 0/7 (0%)
    Vision Blurred 0/23 (0%) 2/21 (9.5%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Eye swelling 1/23 (4.3%) 0/21 (0%) 1/24 (4.2%) 1/6 (16.7%) 0/7 (0%)
    Lacrimation increased 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 1/6 (16.7%) 0/7 (0%)
    Visual disturbance 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Gastrointestinal disorders
    Diarrhoea 8/23 (34.8%) 10/21 (47.6%) 12/24 (50%) 5/6 (83.3%) 5/7 (71.4%)
    Nausea 5/23 (21.7%) 11/21 (52.4%) 8/24 (33.3%) 0/6 (0%) 4/7 (57.1%)
    Vomiting 5/23 (21.7%) 4/21 (19%) 6/24 (25%) 3/6 (50%) 3/7 (42.9%)
    Constipation 4/23 (17.4%) 3/21 (14.3%) 3/24 (12.5%) 1/6 (16.7%) 1/7 (14.3%)
    Frequent Bowel Movements 0/23 (0%) 4/21 (19%) 4/24 (16.7%) 0/6 (0%) 0/7 (0%)
    Abdominal Distension 0/23 (0%) 3/21 (14.3%) 2/24 (8.3%) 1/6 (16.7%) 1/7 (14.3%)
    Abdominal Pain Upper 1/23 (4.3%) 1/21 (4.8%) 3/24 (12.5%) 0/6 (0%) 1/7 (14.3%)
    Dyspepsia 2/23 (8.7%) 3/21 (14.3%) 1/24 (4.2%) 1/6 (16.7%) 2/7 (28.6%)
    Flatulence 0/23 (0%) 3/21 (14.3%) 2/24 (8.3%) 0/6 (0%) 1/7 (14.3%)
    Abdominal Pain 1/23 (4.3%) 1/21 (4.8%) 2/24 (8.3%) 2/6 (33.3%) 1/7 (14.3%)
    Dysphagia 2/23 (8.7%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Hypoaesthesia Oral 0/23 (0%) 2/21 (9.5%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Dry mouth 1/23 (4.3%) 0/21 (0%) 1/24 (4.2%) 1/6 (16.7%) 1/7 (14.3%)
    Gastrooesophageal reflux disease 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 1/6 (16.7%) 0/7 (0%)
    Haemorrhoidal haemorrhage 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Rectal haemorrhage 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 1/6 (16.7%) 0/7 (0%)
    Stomach discomfort 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Abdominal discomfort 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Faeces discoloured 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Toothache 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    General disorders
    Fatigue 8/23 (34.8%) 13/21 (61.9%) 16/24 (66.7%) 5/6 (83.3%) 3/7 (42.9%)
    Pyrexia 8/23 (34.8%) 3/21 (14.3%) 7/24 (29.2%) 3/6 (50%) 1/7 (14.3%)
    Oedema Peripheral 4/23 (17.4%) 3/21 (14.3%) 4/24 (16.7%) 5/6 (83.3%) 0/7 (0%)
    Asthenia 2/23 (8.7%) 1/21 (4.8%) 1/24 (4.2%) 4/6 (66.7%) 3/7 (42.9%)
    Axillary Pain 2/23 (8.7%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Chills 2/23 (8.7%) 1/21 (4.8%) 2/24 (8.3%) 1/6 (16.7%) 1/7 (14.3%)
    Chest discomfort 1/23 (4.3%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Malaise 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 2/6 (33.3%) 0/7 (0%)
    Chest pain 0/23 (0%) 0/21 (0%) 2/24 (8.3%) 0/6 (0%) 0/7 (0%)
    Early satiety 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 1/6 (16.7%) 0/7 (0%)
    Discomfort 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Nodule 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Secretion discharge 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Infections and infestations
    Upper Respiratory Tract Infection 2/23 (8.7%) 5/21 (23.8%) 5/24 (20.8%) 1/6 (16.7%) 1/7 (14.3%)
    Bronchitis 2/23 (8.7%) 2/21 (9.5%) 1/24 (4.2%) 0/6 (0%) 1/7 (14.3%)
    Candidiasis 1/23 (4.3%) 2/21 (9.5%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Gastroenteritis Viral 0/23 (0%) 0/21 (0%) 2/24 (8.3%) 0/6 (0%) 0/7 (0%)
    Influenza 2/23 (8.7%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Pneumonia 0/23 (0%) 0/21 (0%) 2/24 (8.3%) 2/6 (33.3%) 1/7 (14.3%)
    Sinusitis 1/23 (4.3%) 1/21 (4.8%) 2/24 (8.3%) 0/6 (0%) 1/7 (14.3%)
    Urinary Tract Infection 2/23 (8.7%) 2/21 (9.5%) 0/24 (0%) 2/6 (33.3%) 1/7 (14.3%)
    Cellulitis 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 2/6 (33.3%) 0/7 (0%)
    Sepsis 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 2/6 (33.3%) 0/7 (0%)
    Gastroenteritis 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Herpes simplex 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 1/6 (16.7%) 0/7 (0%)
    Clostridium difficile colitis 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Klebsiella bacteraemia 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Pneumonia primary atypical 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Viral infection 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Wound infection 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Injury, poisoning and procedural complications
    Procedural Pain 0/23 (0%) 2/21 (9.5%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Rib fracture 0/23 (0%) 0/21 (0%) 0/24 (0%) 2/6 (33.3%) 0/7 (0%)
    Donor site complication 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Excoriation 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Wound 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Investigations
    Aspartate Aminotransferase Increased 6/23 (26.1%) 4/21 (19%) 3/24 (12.5%) 0/6 (0%) 0/7 (0%)
    Blood Lactate Dehydrogenase Increased 5/23 (21.7%) 3/21 (14.3%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Blood Alkaline Phosphatase Increased 4/23 (17.4%) 3/21 (14.3%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Alanine Aminotransferase Increased 2/23 (8.7%) 3/21 (14.3%) 2/24 (8.3%) 0/6 (0%) 0/7 (0%)
    Blood Bilirubin Increased 1/23 (4.3%) 1/21 (4.8%) 3/24 (12.5%) 0/6 (0%) 0/7 (0%)
    Blood Creatinine Increased 0/23 (0%) 3/21 (14.3%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Blood Bicarbonate Increased 2/23 (8.7%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Blood Phosphorus Decreased 2/23 (8.7%) 0/21 (0%) 2/24 (8.3%) 1/6 (16.7%) 1/7 (14.3%)
    Blood Sodium Decreased 2/23 (8.7%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Haemoglobin Decreased 2/23 (8.7%) 2/21 (9.5%) 2/24 (8.3%) 0/6 (0%) 0/7 (0%)
    Weight Decreased 2/23 (8.7%) 1/21 (4.8%) 2/24 (8.3%) 4/6 (66.7%) 1/7 (14.3%)
    White Blood Cell Count Decreased 1/23 (4.3%) 2/21 (9.5%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Heart rate increased 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Blood potassium decreased 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Breath sounds abnormal 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Cardioactive drug level increased 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Heart sounds abnormal 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Metabolism and nutrition disorders
    Dehydration 3/23 (13%) 0/21 (0%) 4/24 (16.7%) 2/6 (33.3%) 2/7 (28.6%)
    Anorexia 3/23 (13%) 1/21 (4.8%) 1/24 (4.2%) 2/6 (33.3%) 0/7 (0%)
    Hyperglycaemia 3/23 (13%) 1/21 (4.8%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Hypokalaemia 3/23 (13%) 2/21 (9.5%) 2/24 (8.3%) 0/6 (0%) 1/7 (14.3%)
    Hyperkalaemia 0/23 (0%) 0/21 (0%) 2/24 (8.3%) 0/6 (0%) 0/7 (0%)
    Hypocalcaemia 2/23 (8.7%) 1/21 (4.8%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Hypomagnesaemia 2/23 (8.7%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Hyponatraemia 0/23 (0%) 0/21 (0%) 2/24 (8.3%) 0/6 (0%) 1/7 (14.3%)
    Increased Appetite 1/23 (4.3%) 2/21 (9.5%) 2/24 (8.3%) 0/6 (0%) 1/7 (14.3%)
    Hypophosphataemia 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Food craving 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 5/23 (21.7%) 3/21 (14.3%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Muscle Spasms 2/23 (8.7%) 5/21 (23.8%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Back Pain 3/23 (13%) 0/21 (0%) 1/24 (4.2%) 3/6 (50%) 1/7 (14.3%)
    Myalgia 3/23 (13%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Muscular Weakness 0/23 (0%) 1/21 (4.8%) 2/24 (8.3%) 0/6 (0%) 1/7 (14.3%)
    Musculoskeletal Chest Pain 2/23 (8.7%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Musculoskeletal Discomfort 0/23 (0%) 2/21 (9.5%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Shoulder Pain 2/23 (8.7%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Joint swelling 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 2/6 (33.3%) 0/7 (0%)
    Musculoskeletal stiffness 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lymphoma 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Skin neoplasm bleeding 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Squamous cell carcinoma 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Tumour necrosis 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Nervous system disorders
    Headache 4/23 (17.4%) 10/21 (47.6%) 8/24 (33.3%) 0/6 (0%) 3/7 (42.9%)
    Dizziness 1/23 (4.3%) 7/21 (33.3%) 7/24 (29.2%) 3/6 (50%) 2/7 (28.6%)
    Dysgeusia 2/23 (8.7%) 4/21 (19%) 2/24 (8.3%) 0/6 (0%) 2/7 (28.6%)
    Hypoaesthesia 0/23 (0%) 3/21 (14.3%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Neuropathy Peripheral 0/23 (0%) 1/21 (4.8%) 2/24 (8.3%) 0/6 (0%) 1/7 (14.3%)
    Paraesthesia 0/23 (0%) 2/21 (9.5%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Balance disorder 0/23 (0%) 0/21 (0%) 0/24 (0%) 3/6 (50%) 0/7 (0%)
    Lethargy 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Peripheral sensory neuropathy 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 2/7 (28.6%)
    Carpal tunnel syndrome 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Dizziness postural 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Multifocal motor neuropathy 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Sensory disturbance 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Psychiatric disorders
    Anxiety 2/23 (8.7%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 0/7 (0%)
    Insomnia 0/23 (0%) 0/21 (0%) 2/24 (8.3%) 0/6 (0%) 2/7 (28.6%)
    Confusional state 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 2/6 (33.3%) 0/7 (0%)
    Mental status changes 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 2/6 (33.3%) 0/7 (0%)
    Renal and urinary disorders
    Dysuria 1/23 (4.3%) 0/21 (0%) 2/24 (8.3%) 0/6 (0%) 0/7 (0%)
    Renal failure acute 2/23 (8.7%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Nocturia 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 9/23 (39.1%) 5/21 (23.8%) 7/24 (29.2%) 1/6 (16.7%) 2/7 (28.6%)
    Dyspnoea 5/23 (21.7%) 6/21 (28.6%) 9/24 (37.5%) 2/6 (33.3%) 2/7 (28.6%)
    Sinus Congestion 2/23 (8.7%) 3/21 (14.3%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Dyspnoea Exertional 2/23 (8.7%) 2/21 (9.5%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Nasal Congestion 0/23 (0%) 1/21 (4.8%) 2/24 (8.3%) 0/6 (0%) 0/7 (0%)
    Pharyngolaryngeal Pain 2/23 (8.7%) 0/21 (0%) 2/24 (8.3%) 0/6 (0%) 0/7 (0%)
    Productive Cough 2/23 (8.7%) 1/21 (4.8%) 1/24 (4.2%) 0/6 (0%) 0/7 (0%)
    Rhinorrhoea 1/23 (4.3%) 0/21 (0%) 2/24 (8.3%) 0/6 (0%) 1/7 (14.3%)
    Epistaxis 1/23 (4.3%) 1/21 (4.8%) 1/24 (4.2%) 0/6 (0%) 1/7 (14.3%)
    Rales 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Skin and subcutaneous tissue disorders
    Night Sweats 2/23 (8.7%) 3/21 (14.3%) 3/24 (12.5%) 0/6 (0%) 1/7 (14.3%)
    Rash 3/23 (13%) 2/21 (9.5%) 2/24 (8.3%) 1/6 (16.7%) 2/7 (28.6%)
    Erythema 1/23 (4.3%) 1/21 (4.8%) 1/24 (4.2%) 1/6 (16.7%) 0/7 (0%)
    Pruritus 0/23 (0%) 1/21 (4.8%) 1/24 (4.2%) 0/6 (0%) 1/7 (14.3%)
    Alopecia 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Hyperhidrosis 0/23 (0%) 0/21 (0%) 1/24 (4.2%) 0/6 (0%) 1/7 (14.3%)
    Petechiae 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Ecchymosis 0/23 (0%) 1/21 (4.8%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Photodermatosis 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Pruritus generalised 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Vascular disorders
    Hypertension 3/23 (13%) 10/21 (47.6%) 7/24 (29.2%) 0/6 (0%) 4/7 (57.1%)
    Hypotension 1/23 (4.3%) 0/21 (0%) 1/24 (4.2%) 1/6 (16.7%) 0/7 (0%)
    Orthostatic hypotension 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 2/7 (28.6%)
    Subclavian vein thrombosis 1/23 (4.3%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)
    Pallor 0/23 (0%) 0/21 (0%) 0/24 (0%) 0/6 (0%) 1/7 (14.3%)
    Thrombosis 0/23 (0%) 0/21 (0%) 0/24 (0%) 1/6 (16.7%) 0/7 (0%)

    Limitations/Caveats

    This is a small, non-randomized study. Comparisons between the 3 groups cannot be reliably made and should be interpreted with caution.

    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 Anne-Marie Duliege, MD
    Organization Rigel
    Phone 650-624-1100
    Email clinicaltrials@rigel.com
    Responsible Party:
    Rigel Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00446095
    Other Study ID Numbers:
    • D4300C00023
    • C-935788-009
    First Posted:
    Mar 12, 2007
    Last Update Posted:
    Sep 19, 2016
    Last Verified:
    Aug 1, 2016