Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
ClinicalTrials.gov Identifier: NCT00446095
Recruitment Status : Completed
First Posted : March 12, 2007
Results First Posted : December 18, 2014
Last Update Posted : September 19, 2016
Sponsor:
Information provided by (Responsible Party):
Rigel Pharmaceuticals

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphoma
Intervention Drug: fostamatinib
Enrollment 81
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 Details 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
Hide 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
Reason Not Completed
Lost to Follow-up             1             0             0             0             0
Adverse Event             0             1             1             0             0
Withdrawal by Subject             1             0             0             0             0
Physician Decision             1             0             0             0             0
Lack of Efficacy             9             2             1             0             0
Ongoing             0             0             1             0             0
Period Title: Phase I (28 Days)
Started 0 0 0 6 7
Completed 0 0 0 5 4
Not Completed 0 0 0 1 3
Reason Not Completed
Adverse Event             0             0             0             1             0
Lack of Efficacy             0             0             0             0             3
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
Hide 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 Number of Baseline Participants 23 21 24 6 7 81
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 23 participants 21 participants 24 participants 6 participants 7 participants 81 participants
63.0
(41 to 87)
59.0
(41 to 74)
62.0
(51 to 77)
78.5
(70 to 91)
61
(52 to 80)
61.5
(41 to 87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 21 participants 24 participants 6 participants 7 participants 81 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants 21 participants 24 participants 6 participants 7 participants 81 participants
Caucasian 20 19 21 6 5 71
Black/African American 2 0 3 0 1 6
Asian 0 2 0 0 1 3
Other: Russian 1 0 0 0 0 1
1.Primary Outcome
Title Overall Response Rate as Assessed According to the“Revised Response Criteria for Malignant Lymphoma” (Cheson 2007).
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 23 21 24 13
Measure Type: Number
Unit of Measure: Participants
5 2 7 1
2.Primary Outcome
Title Clinical Benefit Rate as Assessed According to the “Revised Response Criteria for Malignant Lymphoma” (Cheson 2007).
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 23 21 24 13
Measure Type: Number
Unit of Measure: Participants
9 13 14 9
3.Secondary Outcome
Title Progression Free Survival (PFS)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 23 21 24
Median (95% Confidence Interval)
Unit of Measure: Days
83.0
(41.0 to 137.0)
141.0
(61.0 to 253.0)
126.0
(64.0 to 169.0)
4.Secondary Outcome
Title Overall Survival (OS)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 23 21 24
Median (95% Confidence Interval)
Unit of Measure: Days
166.0 [1] 
(130.0 to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
[1]
The upper limit of the 95% CI for the median overall survival was not estimable due to small sample size and too few death events and therefore can't be presented.
[2]
The median overall survival could not be calculated due to too few death events.The upper & lower limits of the 95% CI for the median overall survival were not estimable due to small sample size and too few death events, therefore can't be presented.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/23 (60.87%)   7/21 (33.33%)   10/24 (41.67%)   6/6 (100.00%)   3/7 (42.86%) 
Blood and lymphatic system disorders           
Febrile Neutropenia  1  1/23 (4.35%)  1/21 (4.76%)  3/24 (12.50%)  0/6 (0.00%)  1/7 (14.29%) 
Pancytopenia  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Neutropenia  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Cardiac disorders           
Cardio-Respiratory Arrest  1  2/23 (8.70%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Cardiac Arrest  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Myocardial Ischaemia  1  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Cardiac failure  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Gastrointestinal disorders           
Abdominal Pain  1  2/23 (8.70%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Abdominal Pain Upper  1  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Ascites  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Diarrhoea  1  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Duodenal obstruction  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
General disorders           
Pyrexia  1  1/23 (4.35%)  0/21 (0.00%)  2/24 (8.33%)  1/6 (16.67%)  0/7 (0.00%) 
Chest Pain  1  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Infections and infestations           
Pneumonia  1  1/23 (4.35%)  1/21 (4.76%)  2/24 (8.33%)  2/6 (33.33%)  1/7 (14.29%) 
Cellulitis  1  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Gastroenteritis Viral  1  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Lung Infection Pseudomonal  1  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Pneumococcal Sepsis  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Sepsis  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  2/6 (33.33%)  0/7 (0.00%) 
Staphylococcal Infection  1  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Urinary Tract Infection  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  2/6 (33.33%)  0/7 (0.00%) 
Klebsiella bacteraemia  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Metabolism and nutrition disorders           
Dehydration  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Musculoskeletal and connective tissue disorders           
Pathological Fracture  1  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Squamous cell carcinoma  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Tumour necrosis  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Nervous system disorders           
Lethargy  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Spinal Cord Compression  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Syncope  1  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Multifocal motor neuropathy  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Psychiatric disorders           
Mental Status Changes  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Renal and urinary disorders           
Renal Failure  1  0/23 (0.00%)  1/21 (4.76%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Renal Failure Acute  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Acute Respiratory Distress Syndrome  1  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Dyspnoea Exacerbated  1  1/23 (4.35%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Hypoxia  1  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Dyspnoea  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Vascular disorders           
Superior Vena Caval Occlusion  1  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/23 (95.65%)   21/21 (100.00%)   24/24 (100.00%)   6/6 (100.00%)   6/7 (85.71%) 
Blood and lymphatic system disorders           
Anaemia  1  5/23 (21.74%)  7/21 (33.33%)  9/24 (37.50%)  4/6 (66.67%)  2/7 (28.57%) 
Thrombocytopenia  1  7/23 (30.43%)  5/21 (23.81%)  8/24 (33.33%)  4/6 (66.67%)  1/7 (14.29%) 
Leukopenia  1  1/23 (4.35%)  7/21 (33.33%)  2/24 (8.33%)  4/6 (66.67%)  1/7 (14.29%) 
Neutropenia  1  7/23 (30.43%)  9/21 (42.86%)  11/24 (45.83%)  4/6 (66.67%)  2/7 (28.57%) 
Febrile neutropenia  1/23 (4.35%)  1/21 (4.76%)  3/24 (12.50%)  0/6 (0.00%)  1/7 (14.29%) 
Bone marrow failure  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Cardiac disorders           
Tachycardia  1  3/23 (13.04%)  0/21 (0.00%)  2/24 (8.33%)  1/6 (16.67%)  1/7 (14.29%) 
Atrial fibrillation  0/23 (0.00%)  1/21 (4.76%)  1/24 (4.17%)  1/6 (16.67%)  0/7 (0.00%) 
Cardiac failure congestive  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  2/6 (33.33%)  0/7 (0.00%) 
Cardiac failure  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  1/6 (16.67%)  0/7 (0.00%) 
Myocardial ischaemia  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  1/7 (14.29%) 
Palpitations  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Arrhythmia  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Intracardiac thrombus  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Ventricular tachycardia  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Ear and labyrinth disorders           
Tinnitus  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Eye disorders           
Conjunctival Haemorrhage  1  0/23 (0.00%)  0/21 (0.00%)  2/24 (8.33%)  0/6 (0.00%)  0/7 (0.00%) 
Vision Blurred  1  0/23 (0.00%)  2/21 (9.52%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Eye swelling  1/23 (4.35%)  0/21 (0.00%)  1/24 (4.17%)  1/6 (16.67%)  0/7 (0.00%) 
Lacrimation increased  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  1/6 (16.67%)  0/7 (0.00%) 
Visual disturbance  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Gastrointestinal disorders           
Diarrhoea  1  8/23 (34.78%)  10/21 (47.62%)  12/24 (50.00%)  5/6 (83.33%)  5/7 (71.43%) 
Nausea  1  5/23 (21.74%)  11/21 (52.38%)  8/24 (33.33%)  0/6 (0.00%)  4/7 (57.14%) 
Vomiting  1  5/23 (21.74%)  4/21 (19.05%)  6/24 (25.00%)  3/6 (50.00%)  3/7 (42.86%) 
Constipation  1  4/23 (17.39%)  3/21 (14.29%)  3/24 (12.50%)  1/6 (16.67%)  1/7 (14.29%) 
Frequent Bowel Movements  1  0/23 (0.00%)  4/21 (19.05%)  4/24 (16.67%)  0/6 (0.00%)  0/7 (0.00%) 
Abdominal Distension  1  0/23 (0.00%)  3/21 (14.29%)  2/24 (8.33%)  1/6 (16.67%)  1/7 (14.29%) 
Abdominal Pain Upper  1  1/23 (4.35%)  1/21 (4.76%)  3/24 (12.50%)  0/6 (0.00%)  1/7 (14.29%) 
Dyspepsia  1  2/23 (8.70%)  3/21 (14.29%)  1/24 (4.17%)  1/6 (16.67%)  2/7 (28.57%) 
Flatulence  1  0/23 (0.00%)  3/21 (14.29%)  2/24 (8.33%)  0/6 (0.00%)  1/7 (14.29%) 
Abdominal Pain  1  1/23 (4.35%)  1/21 (4.76%)  2/24 (8.33%)  2/6 (33.33%)  1/7 (14.29%) 
Dysphagia  1  2/23 (8.70%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Hypoaesthesia Oral  1  0/23 (0.00%)  2/21 (9.52%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Dry mouth  1/23 (4.35%)  0/21 (0.00%)  1/24 (4.17%)  1/6 (16.67%)  1/7 (14.29%) 
Gastrooesophageal reflux disease  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  1/6 (16.67%)  0/7 (0.00%) 
Haemorrhoidal haemorrhage  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Rectal haemorrhage  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  1/6 (16.67%)  0/7 (0.00%) 
Stomach discomfort  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Abdominal discomfort  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Faeces discoloured  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Toothache  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
General disorders           
Fatigue  1  8/23 (34.78%)  13/21 (61.90%)  16/24 (66.67%)  5/6 (83.33%)  3/7 (42.86%) 
Pyrexia  1  8/23 (34.78%)  3/21 (14.29%)  7/24 (29.17%)  3/6 (50.00%)  1/7 (14.29%) 
Oedema Peripheral  1  4/23 (17.39%)  3/21 (14.29%)  4/24 (16.67%)  5/6 (83.33%)  0/7 (0.00%) 
Asthenia  1  2/23 (8.70%)  1/21 (4.76%)  1/24 (4.17%)  4/6 (66.67%)  3/7 (42.86%) 
Axillary Pain  1  2/23 (8.70%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Chills  1  2/23 (8.70%)  1/21 (4.76%)  2/24 (8.33%)  1/6 (16.67%)  1/7 (14.29%) 
Chest discomfort  1/23 (4.35%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Malaise  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  2/6 (33.33%)  0/7 (0.00%) 
Chest pain  0/23 (0.00%)  0/21 (0.00%)  2/24 (8.33%)  0/6 (0.00%)  0/7 (0.00%) 
Early satiety  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  1/6 (16.67%)  0/7 (0.00%) 
Discomfort  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Nodule  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Secretion discharge  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Infections and infestations           
Upper Respiratory Tract Infection  1  2/23 (8.70%)  5/21 (23.81%)  5/24 (20.83%)  1/6 (16.67%)  1/7 (14.29%) 
Bronchitis  1  2/23 (8.70%)  2/21 (9.52%)  1/24 (4.17%)  0/6 (0.00%)  1/7 (14.29%) 
Candidiasis  1  1/23 (4.35%)  2/21 (9.52%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Gastroenteritis Viral  1  0/23 (0.00%)  0/21 (0.00%)  2/24 (8.33%)  0/6 (0.00%)  0/7 (0.00%) 
Influenza  1  2/23 (8.70%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Pneumonia  1  0/23 (0.00%)  0/21 (0.00%)  2/24 (8.33%)  2/6 (33.33%)  1/7 (14.29%) 
Sinusitis  1  1/23 (4.35%)  1/21 (4.76%)  2/24 (8.33%)  0/6 (0.00%)  1/7 (14.29%) 
Urinary Tract Infection  1  2/23 (8.70%)  2/21 (9.52%)  0/24 (0.00%)  2/6 (33.33%)  1/7 (14.29%) 
Cellulitis  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  2/6 (33.33%)  0/7 (0.00%) 
Sepsis  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  2/6 (33.33%)  0/7 (0.00%) 
Gastroenteritis  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Herpes simplex  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  1/6 (16.67%)  0/7 (0.00%) 
Clostridium difficile colitis  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Klebsiella bacteraemia  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Pneumonia primary atypical  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Viral infection  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Wound infection  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Injury, poisoning and procedural complications           
Procedural Pain  1  0/23 (0.00%)  2/21 (9.52%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Rib fracture  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  2/6 (33.33%)  0/7 (0.00%) 
Donor site complication  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Excoriation  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Wound  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Investigations           
Aspartate Aminotransferase Increased  1  6/23 (26.09%)  4/21 (19.05%)  3/24 (12.50%)  0/6 (0.00%)  0/7 (0.00%) 
Blood Lactate Dehydrogenase Increased  1  5/23 (21.74%)  3/21 (14.29%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Blood Alkaline Phosphatase Increased  1  4/23 (17.39%)  3/21 (14.29%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Alanine Aminotransferase Increased  1  2/23 (8.70%)  3/21 (14.29%)  2/24 (8.33%)  0/6 (0.00%)  0/7 (0.00%) 
Blood Bilirubin Increased  1  1/23 (4.35%)  1/21 (4.76%)  3/24 (12.50%)  0/6 (0.00%)  0/7 (0.00%) 
Blood Creatinine Increased  1  0/23 (0.00%)  3/21 (14.29%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Blood Bicarbonate Increased  1  2/23 (8.70%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Blood Phosphorus Decreased  1  2/23 (8.70%)  0/21 (0.00%)  2/24 (8.33%)  1/6 (16.67%)  1/7 (14.29%) 
Blood Sodium Decreased  1  2/23 (8.70%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Haemoglobin Decreased  1  2/23 (8.70%)  2/21 (9.52%)  2/24 (8.33%)  0/6 (0.00%)  0/7 (0.00%) 
Weight Decreased  1  2/23 (8.70%)  1/21 (4.76%)  2/24 (8.33%)  4/6 (66.67%)  1/7 (14.29%) 
White Blood Cell Count Decreased  1  1/23 (4.35%)  2/21 (9.52%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Heart rate increased  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Blood potassium decreased  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Breath sounds abnormal  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Cardioactive drug level increased  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Heart sounds abnormal  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Metabolism and nutrition disorders           
Dehydration  1  3/23 (13.04%)  0/21 (0.00%)  4/24 (16.67%)  2/6 (33.33%)  2/7 (28.57%) 
Anorexia  1  3/23 (13.04%)  1/21 (4.76%)  1/24 (4.17%)  2/6 (33.33%)  0/7 (0.00%) 
Hyperglycaemia  1  3/23 (13.04%)  1/21 (4.76%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Hypokalaemia  1  3/23 (13.04%)  2/21 (9.52%)  2/24 (8.33%)  0/6 (0.00%)  1/7 (14.29%) 
Hyperkalaemia  1  0/23 (0.00%)  0/21 (0.00%)  2/24 (8.33%)  0/6 (0.00%)  0/7 (0.00%) 
Hypocalcaemia  1  2/23 (8.70%)  1/21 (4.76%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Hypomagnesaemia  1  2/23 (8.70%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Hyponatraemia  1  0/23 (0.00%)  0/21 (0.00%)  2/24 (8.33%)  0/6 (0.00%)  1/7 (14.29%) 
Increased Appetite  1  1/23 (4.35%)  2/21 (9.52%)  2/24 (8.33%)  0/6 (0.00%)  1/7 (14.29%) 
Hypophosphataemia  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Food craving  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  5/23 (21.74%)  3/21 (14.29%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Muscle Spasms  1  2/23 (8.70%)  5/21 (23.81%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Back Pain  1  3/23 (13.04%)  0/21 (0.00%)  1/24 (4.17%)  3/6 (50.00%)  1/7 (14.29%) 
Myalgia  1  3/23 (13.04%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Muscular Weakness  1  0/23 (0.00%)  1/21 (4.76%)  2/24 (8.33%)  0/6 (0.00%)  1/7 (14.29%) 
Musculoskeletal Chest Pain  1  2/23 (8.70%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Musculoskeletal Discomfort  1  0/23 (0.00%)  2/21 (9.52%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Shoulder Pain  1  2/23 (8.70%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Joint swelling  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  2/6 (33.33%)  0/7 (0.00%) 
Musculoskeletal stiffness  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Lymphoma  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Skin neoplasm bleeding  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Squamous cell carcinoma  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Tumour necrosis  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Nervous system disorders           
Headache  1  4/23 (17.39%)  10/21 (47.62%)  8/24 (33.33%)  0/6 (0.00%)  3/7 (42.86%) 
Dizziness  1  1/23 (4.35%)  7/21 (33.33%)  7/24 (29.17%)  3/6 (50.00%)  2/7 (28.57%) 
Dysgeusia  1  2/23 (8.70%)  4/21 (19.05%)  2/24 (8.33%)  0/6 (0.00%)  2/7 (28.57%) 
Hypoaesthesia  1  0/23 (0.00%)  3/21 (14.29%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Neuropathy Peripheral  1  0/23 (0.00%)  1/21 (4.76%)  2/24 (8.33%)  0/6 (0.00%)  1/7 (14.29%) 
Paraesthesia  1  0/23 (0.00%)  2/21 (9.52%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Balance disorder  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  3/6 (50.00%)  0/7 (0.00%) 
Lethargy  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Peripheral sensory neuropathy  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  2/7 (28.57%) 
Carpal tunnel syndrome  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Dizziness postural  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Multifocal motor neuropathy  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Sensory disturbance  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Psychiatric disorders           
Anxiety  1  2/23 (8.70%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  0/7 (0.00%) 
Insomnia  1  0/23 (0.00%)  0/21 (0.00%)  2/24 (8.33%)  0/6 (0.00%)  2/7 (28.57%) 
Confusional state  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  2/6 (33.33%)  0/7 (0.00%) 
Mental status changes  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  2/6 (33.33%)  0/7 (0.00%) 
Renal and urinary disorders           
Dysuria  1  1/23 (4.35%)  0/21 (0.00%)  2/24 (8.33%)  0/6 (0.00%)  0/7 (0.00%) 
Renal failure acute  2/23 (8.70%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Nocturia  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  9/23 (39.13%)  5/21 (23.81%)  7/24 (29.17%)  1/6 (16.67%)  2/7 (28.57%) 
Dyspnoea  1  5/23 (21.74%)  6/21 (28.57%)  9/24 (37.50%)  2/6 (33.33%)  2/7 (28.57%) 
Sinus Congestion  1  2/23 (8.70%)  3/21 (14.29%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Dyspnoea Exertional  1  2/23 (8.70%)  2/21 (9.52%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Nasal Congestion  1  0/23 (0.00%)  1/21 (4.76%)  2/24 (8.33%)  0/6 (0.00%)  0/7 (0.00%) 
Pharyngolaryngeal Pain  1  2/23 (8.70%)  0/21 (0.00%)  2/24 (8.33%)  0/6 (0.00%)  0/7 (0.00%) 
Productive Cough  1  2/23 (8.70%)  1/21 (4.76%)  1/24 (4.17%)  0/6 (0.00%)  0/7 (0.00%) 
Rhinorrhoea  1  1/23 (4.35%)  0/21 (0.00%)  2/24 (8.33%)  0/6 (0.00%)  1/7 (14.29%) 
Epistaxis  1/23 (4.35%)  1/21 (4.76%)  1/24 (4.17%)  0/6 (0.00%)  1/7 (14.29%) 
Rales  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Skin and subcutaneous tissue disorders           
Night Sweats  1  2/23 (8.70%)  3/21 (14.29%)  3/24 (12.50%)  0/6 (0.00%)  1/7 (14.29%) 
Rash  1  3/23 (13.04%)  2/21 (9.52%)  2/24 (8.33%)  1/6 (16.67%)  2/7 (28.57%) 
Erythema  1/23 (4.35%)  1/21 (4.76%)  1/24 (4.17%)  1/6 (16.67%)  0/7 (0.00%) 
Pruritus  0/23 (0.00%)  1/21 (4.76%)  1/24 (4.17%)  0/6 (0.00%)  1/7 (14.29%) 
Alopecia  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Hyperhidrosis  0/23 (0.00%)  0/21 (0.00%)  1/24 (4.17%)  0/6 (0.00%)  1/7 (14.29%) 
Petechiae  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Ecchymosis  0/23 (0.00%)  1/21 (4.76%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Photodermatosis  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Pruritus generalised  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Vascular disorders           
Hypertension  1  3/23 (13.04%)  10/21 (47.62%)  7/24 (29.17%)  0/6 (0.00%)  4/7 (57.14%) 
Hypotension  1/23 (4.35%)  0/21 (0.00%)  1/24 (4.17%)  1/6 (16.67%)  0/7 (0.00%) 
Orthostatic hypotension  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  2/7 (28.57%) 
Subclavian vein thrombosis  1/23 (4.35%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Pallor  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  0/6 (0.00%)  1/7 (14.29%) 
Thrombosis  0/23 (0.00%)  0/21 (0.00%)  0/24 (0.00%)  1/6 (16.67%)  0/7 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.0
This is a small, non-randomized study. Comparisons between the 3 groups cannot be reliably made and should be interpreted with caution.
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
Responsible Party: Rigel Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00446095     History of Changes
Other Study ID Numbers: D4300C00023
C-935788-009 ( Other Identifier: Rigel Pharmaceuticals )
First Submitted: March 8, 2007
First Posted: March 12, 2007
Results First Submitted: May 14, 2014
Results First Posted: December 18, 2014
Last Update Posted: September 19, 2016