ABI-007 In Combination With Bevacizumab in Women With Metastatic Breast Cancer

• Sponsor: Celgene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00394082
• Collaborator: (none)
• Enrollment: 50
• Locations: 20
• Arm: 1
• Actual Duration (Months): 56
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of weekly ABI-007 in combination with bevacizumab.

The evaluation of progression-free survival of weekly ABI-007 in combination with bevacizumab for patients with previously untreated advanced/metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: ABI-007; Drug: Bevacizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Weekly Administration of ABI-007 In Combination With Bevacizumab in Women With Metastatic Breast Cancer
• Actual Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: ABI-007 plus Bevacizumab ABI-007 is administered on days 1, 8 and 15 at 125 mg/m^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient.

Drug: ABI-007; 125 mg/m^2 of ABI-007 administered by intravenously (IV) over 30 minutes on days 1, 8 and 15 of each 28 day cycle.; Other Names: Abraxane® Nab-paclitaxel ; Drug: Bevacizumab; Bevacizumab administered once every 2 weeks (10 mg/kg) by IV infusion after ABI-007 has been given. The first dose is one Day 1, cycle 1.; Other Names: NSC 704865 RhuMAb VEGF Recombinant Humanized Monoclonal Bevacizumab Antibody

Outcome Measures

Primary Outcome Measures

1. Participants With At Least One Treatment-Emergent Adverse Event (TEAE) [up to 25 months]

   Count of study participants who had at least one treatment-emergent adverse event (TEAE) defined as any adverse event that began or worsened in grade after the start of study drug through 30 days after the last dose of study drug.

2. Kaplan-Meier Estimates for Progression-free Survival [up to 39 months]

   Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first. Patients who do not have disease progression or have not died at the end of follow-up were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Response Evaluation Criteria in Solid Tumors (RECIST) defines progressive disease (PD) as a >= 20% increase taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

Secondary Outcome Measures

1. Percentage of Participants With Objective Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) [up to 39 months]

   Objective response is complete response (CR) + partial response (PR). RECIST defines overall response of CR as the disappearance of all target and non-target lesions and no appearance of new lesions, confirmed at least 4 weeks after initial documentation. Overall response of PR is defined as >= 30% decrease from baseline in the sum of the longest diameters of target lesions and no progression of non-target lesions and no appearance of new lesions, confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing and no appearance of new lesions. The objective response is determined by combining the response of target and non-target lesions and the appearance of new lesion(s) or not together.

2. Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST) [up to 39 months]

   Disease control is stable disease (SD) for >=16 weeks + complete response (CR) + partial response (PR). RECIST defines SD as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease and no new lesions. Definitions for CR and PR can be found in outcome #3.

3. Kaplan-Meier Estimate for Duration of Response [up to 39 months]

   Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Patients that did not have progression or have not died were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Progressive disease is defined in outcome #2. Complete response (CR) and partial response (PR) are defined in outcome #3.

4. Kaplan-Meier Estimates for Participant Survival [up to 39 months]

   Participant survival is the time from the first dose of study drug to patient death from any cause. Patients that did not die were censored at the last known time the patient was alive.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pathologically confirmed adenocarcinoma of the breast.

• Stage IV disease.

• Measurable disease (defined as the presence of at least one lesion that can be accurately measured in at least one dimension with longest diameter greater or = 1.0 cm with spiral computed tomography (CT) scan).

• Patients must not be a candidate for Herceptin therapy (i.e., patients with HER-2 positive disease (gene amplification by fluorescence in situ hybridization (FISH) or 3

• overexpression by ICH) and patients with unknown HER-2 status are ineligible unless the treating physicians has determined that Herceptin-based therapy would be inappropriate or not indicated).

• For subjects with prior anthracycline exposure, normal cardiac function including a baseline left ventricle ejection fraction >50% or above institution's lower limit of normal and a normal electrocardiogram (ECG) (as assessed by the investigator).

• At least 2 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be pathologic proof of progressive disease within the radiation portal.

• International Normalized Ratio (INR) < 1.5 and activated partial thromboplastin time within normal limits (APTT WNL).

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

• Female > 18 years of age.

• Patients have the following blood counts at Baseline: absolute neutrophil count (ANC) greater or equal to 1.5 x 10^{9 cells/L; platelets greater or equal 100 x 10}9 cells/L; hemoglobin (Hgb) greater or equal to 9g/dL.

• Patients have the following blood chemistry levels at Baseline: aspartate aminotransferase (AST or SGOT), alanine aminotransferase (ALT or SGPT) less than or equal 2.5x upper limit of normal (ULN) range (less than or equal 5x ULN if patient has known liver metastases); total bilirubin greater than or equal to ULN; creatinine greater or equal to 1.5mg/dL.

• if female of childbearing potential, pregnancy test is negative within 72 hours of first dose of study drug.

• if fertile, the patient agrees to use an effective method to avoid pregnancy for the duration of the study.

• Informed consent has been obtained.

Exclusion Criteria:

• No prior chemotherapy for metastatic or locally recurrent disease is allowed.

• Prio neo-adjuvant chemotherapy is allowed, and patients must have recovered from the acute toxicity of such therapies.

• if a taxane was part of the adjuvant regimen, at least 12 months must have elapsed between the last dose of the taxane and the date of diagnosis of metastatic disease.

• if a non-taxane-based adjuvant therapy was administered, at least six months must have elapsed between the last dose of the non- taxane-containing chemotherapy and the date of diagnosis of metastatic disease.

• Concurrent immunotherapy or hormonal therapy.

• Parenchymal brain metastases, including leptomeningeal involvement.

• Uncontrolled hypertension (defined as blood pressure of > 150/100 mmHg)

• NYHA Grade 2 or greater congestive heart failure

• History of coagulopathy, bleeding diathesis, therapeutic anticoagulation other than low dose or chronic ASA greater than or equal to 325 mg per day. Low dose coumadin for anticoagulation of venous access device or low dose molecular weight heparin (LMWH)for deep vein thrombosis prophylaxis or low dose (325 mg or less) ASA prophylaxis are allowed, but are best avoided if the treating physician feels it is safe to do so.

• Urine protein:creatinine ratio less than or equal to 1.0 at screening.

• No history of cerebrovascular accident within six months of study entry.

• Active symptomatic peripheral vascular disease (e.g. aortic aneurysm, claudication) within six months of study entry.

• Uncontrolled or severe cardiovascular disease including myocardial infarction or unstable angina within six months of study entry.

• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal process within six months of study entry.

• No serious non-healing wound, ulcer, or bone fracture

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first dose, or anticipation of need for major surgical procedure during the course of the study. No minor surgical procedure within seven days of study entry. Serious intercurrent medical or psychiatric illness, including serious active infection.

• History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.

• Pregnant or nursing women.

• Patients with current sensory neuropathy of > Grade 1 will be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Melbourne	Florida	United States	32901
2		Ocoee	Florida	United States	34761
3		Niles	Illinois	United States	60714
4		Terre Haute	Indiana	United States	47802
5		Columbia	Maryland	United States	21044
6		Westminister	Maryland	United States	21157
7		Saint Joseph	Missouri	United States	64507
8		Rochester	New York	United States	14623
9		Bedford	Texas	United States	76022
10		Dallas	Texas	United States	75246
11		El Paso	Texas	United States	79915
12		Odessa	Texas	United States	79761
13		San Antonio	Texas	United States	78229
14		Tyler	Texas	United States	75702
15		Fairfax	Virginia	United States	22031
16		Norfolk	Virginia	United States	23502
17		Salem	Virginia	United States	24153
18		Burien	Washington	United States	98166
19		Edmonds	Washington	United States	98026
20		Vancouver	Washington	United States	98684

Sponsors and Collaborators

• Celgene

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Danso M, et al. Phase II trial of weekly nab-paclitaxel in combination with bevacizumab as first-line treatment in metastatic breast cancer. Presented at 2008 ASCO Annual Meeting, May 30-June 3, 2008, Chicago, IL. Abstract No. 1075.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT00394082
• Other Study ID Numbers: CA043
• First Posted: Oct 31, 2006
• Last Update Posted: Nov 25, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Celgene: Metastatic breast cancer, Abraxane, Bevacizumab
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Bevacizumab; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Arm/Group Title	ABI-007 Plus Bevacizumab
Arm/Group Description	ABI-007 is administered on days 1, 8 and 15 at 125 mg/m^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient.
Period Title: Overall Study
STARTED	50
At Least One Response Assessment	43
COMPLETED	24
NOT COMPLETED	26

Baseline Characteristics

Arm/Group Title	ABI-007 Plus Bevacizumab
Arm/Group Description	ABI-007 is administered on days 1, 8 and 15 at 125 mg/m^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient.
Overall Participants	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.6 (11.03)
Sex: Female, Male (Count of Participants)
Female	50 100%
Male	0 0%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 6%
White, Non-Hispanic and Non-Latino	40 80%
White, Hispanic or Latino	7 14%
Other	0 0%
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	74.52 (15.430)
Menopausal status (participants) [Number]
Pre-menopausal	7 14%
Post-menopausal	43 86%
Eastern Cooperative Oncology Group (ECOG) status (participants) [Number]
0 (Fully Active)	23 46%
1 (Restrictive but Ambulatory)	25 50%
2 (Ambulatory but Unable to Work)	2 4%
3 (Limited Self-Care)	0 0%
4 (Completely Disabled)	0 0%
Time from First Documented Metastasis/Relapse to Study Entry (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	1.01 (3.123)
Dominant Current Site of Metastasis/Relapse (participants) [Number]
Visceral	49 98%
Non Visceral	1 2%

Outcome Measures

1. Primary Outcome

Title	Participants With At Least One Treatment-Emergent Adverse Event (TEAE)
Description	Count of study participants who had at least one treatment-emergent adverse event (TEAE) defined as any adverse event that began or worsened in grade after the start of study drug through 30 days after the last dose of study drug.
Time Frame	up to 25 months

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	ABI-007 Plus Bevacizumab
Arm/Group Description	ABI-007 is administered on days 1, 8 and 15 at 125 mg/m^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient.
Measure Participants	50
Number [participants]	50 100%

2. Primary Outcome

Title	Kaplan-Meier Estimates for Progression-free Survival
Description	Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first. Patients who do not have disease progression or have not died at the end of follow-up were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Response Evaluation Criteria in Solid Tumors (RECIST) defines progressive disease (PD) as a >= 20% increase taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.
Time Frame	up to 39 months

Outcome Measure Data

Analysis Population Description

Treated population.

Arm/Group Title	ABI-007 Plus Bevacizumab
Arm/Group Description	ABI-007 is administered on days 1, 8 and 15 at 125 mg/m^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient.
Measure Participants	50
Median (95% Confidence Interval) [months]	8.0

3. Secondary Outcome

Title	Percentage of Participants With Objective Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
Description	Objective response is complete response (CR) + partial response (PR). RECIST defines overall response of CR as the disappearance of all target and non-target lesions and no appearance of new lesions, confirmed at least 4 weeks after initial documentation. Overall response of PR is defined as >= 30% decrease from baseline in the sum of the longest diameters of target lesions and no progression of non-target lesions and no appearance of new lesions, confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing and no appearance of new lesions. The objective response is determined by combining the response of target and non-target lesions and the appearance of new lesion(s) or not together.
Time Frame	up to 39 months

Outcome Measure Data

Analysis Population Description

Treated population.

Arm/Group Title	ABI-007 Plus Bevacizumab
Arm/Group Description	ABI-007 is administered on days 1, 8 and 15 at 125 mg/m^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient.
Measure Participants	50
Overall response (CR + PR)	30 60%
Complete response (CR)	0 0%
Partial response (PR)	30 60%

4. Secondary Outcome

Title	Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
Description	Disease control is stable disease (SD) for >=16 weeks + complete response (CR) + partial response (PR). RECIST defines SD as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease and no new lesions. Definitions for CR and PR can be found in outcome #3.
Time Frame	up to 39 months

Outcome Measure Data

Analysis Population Description

Treated population

Arm/Group Title	ABI-007 Plus Bevacizumab
Arm/Group Description	ABI-007 is administered on days 1, 8 and 15 at 125 mg/m^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient.
Measure Participants	50
CR + PR + SD>=16 weeks	50 100%
Complete response (CR)	0 0%
Partial response (PR)	30 60%
Stable disease >=16 weeks (SD>=16 weeks)	20 40%

5. Secondary Outcome

Title	Kaplan-Meier Estimate for Duration of Response
Description	Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Patients that did not have progression or have not died were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Progressive disease is defined in outcome #2. Complete response (CR) and partial response (PR) are defined in outcome #3.
Time Frame	up to 39 months

Outcome Measure Data

Analysis Population Description

Treated population of participants who had a response.

Arm/Group Title	ABI-007 Plus Bevacizumab
Arm/Group Description	ABI-007 is administered on days 1, 8 and 15 at 125 mg/m^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient.
Measure Participants	15
Median (95% Confidence Interval) [months]	10.3

6. Secondary Outcome

Title	Kaplan-Meier Estimates for Participant Survival
Description	Participant survival is the time from the first dose of study drug to patient death from any cause. Patients that did not die were censored at the last known time the patient was alive.
Time Frame	up to 39 months

Outcome Measure Data

Analysis Population Description

Treated population

Arm/Group Title	ABI-007 Plus Bevacizumab
Arm/Group Description	ABI-007 is administered on days 1, 8 and 15 at 125 mg/m^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient.
Measure Participants	50
Median (95% Confidence Interval) [months]	17.1

Adverse Events

Time Frame	up to 25 months
Arm/Group Title	ABI-007 Plus Bevacizumab
Arm/Group Description	ABI-007 is administered on days 1, 8 and 15 at 125 mg/m^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient.
All Cause Mortality
	ABI-007 Plus Bevacizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	ABI-007 Plus Bevacizumab
	Affected / at Risk (%)	# Events
Total	13/50 (26%)
Blood and lymphatic system disorders
Febrile neutropenia	3/50 (6%)
Neutropenia	1/50 (2%)
Gastrointestinal disorders
Pancreatitis	1/50 (2%)
Hepatobiliary disorders
Cholangitis	1/50 (2%)
Cholelithiasis	1/50 (2%)
Immune system disorders
Anaphylactic reaction	1/50 (2%)
Infections and infestations
Pneumonia	1/50 (2%)
Injury, poisoning and procedural complications
Pneumonitis chemical	1/50 (2%)
Spinal compression fracture	1/50 (2%)
Metabolism and nutrition disorders
Dehydration	1/50 (2%)
Electrolyte imbalance	1/50 (2%)
Hypovolaemia	1/50 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges	1/50 (2%)
Nervous system disorders
Dizziness	1/50 (2%)
Psychiatric disorders
Bipolar disorder	1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/50 (2%)
Pulmonary embolism	1/50 (2%)
Other (Not Including Serious) Adverse Events
	ABI-007 Plus Bevacizumab
	Affected / at Risk (%)	# Events
Total	50/50 (100%)
Blood and lymphatic system disorders
Neutropenia	20/50 (40%)
Anaemia	14/50 (28%)
Leukopenia	5/50 (10%)
Cardiac disorders
Palpitations	3/50 (6%)
Eye disorders
Vision blurred	5/50 (10%)
Conjunctivitis	4/50 (8%)
Lacrimation increased	3/50 (6%)
Gastrointestinal disorders
Nausea	34/50 (68%)
Diarrhoea	19/50 (38%)
Constipation	16/50 (32%)
Vomiting	13/50 (26%)
Abdominal distension	7/50 (14%)
Abdominal pain	7/50 (14%)
Stomatitis	6/50 (12%)
Dyspepsia	4/50 (8%)
Gastrooesophageal reflux disease	4/50 (8%)
Abdominal pain upper	3/50 (6%)
Flatulence	3/50 (6%)
General disorders
Fatigue	35/50 (70%)
Oedema peripheral	12/50 (24%)
Asthenia	9/50 (18%)
Mucosal inflammation	8/50 (16%)
Pyrexia	7/50 (14%)
Pain	6/50 (12%)
Chills	5/50 (10%)
Infusion site pain	3/50 (6%)
Infections and infestations
Urinary tract infection	11/50 (22%)
Upper respiratory tract infection	7/50 (14%)
Cellulitis	3/50 (6%)
Vulvovaginal mycotic infection	3/50 (6%)
Investigations
Weight decreased	4/50 (8%)
Neutrophil count decreased	3/50 (6%)
White blood cell count decreased	3/50 (6%)
Metabolism and nutrition disorders
Anorexia	9/50 (18%)
Decreased appetite	5/50 (10%)
Dehydration	4/50 (8%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/50 (20%)
Pain in extremity	7/50 (14%)
Back pain	5/50 (10%)
Muscle spasms	5/50 (10%)
Myalgia	4/50 (8%)
Neck pain	3/50 (6%)
Nervous system disorders
Headache	18/50 (36%)
Neuropathy	15/50 (30%)
Neuropathy peripheral	13/50 (26%)
Peripheral sensory neuropathy	13/50 (26%)
Dizziness	8/50 (16%)
Dysgeusia	8/50 (16%)
Hypoaesthesia	3/50 (6%)
Paraesthesia	3/50 (6%)
Psychiatric disorders
Insomnia	12/50 (24%)
Anxiety	5/50 (10%)
Renal and urinary disorders
Dysuria	6/50 (12%)
Proteinuria	4/50 (8%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	26/50 (52%)
Dyspnoea	17/50 (34%)
Cough	13/50 (26%)
Pharyngolaryngeal pain	9/50 (18%)
Nasal congestion	6/50 (12%)
Rhinorrhoea	6/50 (12%)
Sinus congestion	4/50 (8%)
Dysphonia	3/50 (6%)
Pulmonary congestion	3/50 (6%)
Skin and subcutaneous tissue disorders
Alopecia	31/50 (62%)
Nail disorder	12/50 (24%)
Rash	11/50 (22%)
Dermatitis acneiform	5/50 (10%)
Dry skin	4/50 (8%)
Erythema	4/50 (8%)
Nail discolouration	4/50 (8%)
Vascular disorders
Hypertension	14/50 (28%)
Hot flush	4/50 (8%)
Hypotension	3/50 (6%)
Lymphoedema	3/50 (6%)

Limitations/Caveats

Interpretation of results is limited since the cell receptor subtype status of patients is not known.

More Information

Certain Agreements

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

Results from a center cannot be submitted for publication before results of multicenter study are published unless it has been more than 2 years since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decided publication would hinder patent applications, Investigator must delay submission for up to 1 year. Investigator must delete confidential information before submission.