Epratuzumab and Rituximab in Treating Patients With Previously Untreated Follicular Non-Hodgkin Lymphoma

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00553501
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 60
• Locations: 43
• Arm: 1
• Duration (Months): 76
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as epratuzumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving epratuzumab and rituximab together may be more effective in treating follicular non-Hodgkin lymphoma.

PURPOSE: This phase II trial is studying how well giving epratuzumab together with rituximab works in treating patients with previously untreated follicular non-Hodgkin lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: epratuzumab; Biological: rituximab	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine the response rate (overall and complete) after extended induction therapy comprising epratuzumab and rituximab in patients with previously untreated CD20+ follicular non-Hodgkin lymphoma (NHL).

• To determine the time to progression after extended induction therapy comprising epratuzumab and rituximab in patients with previously untreated CD20+ follicular NHL.

Secondary

• To determine the toxicity profile of epratuzumab and rituximab in patients with previously untreated CD20+ follicular NHL.

• To establish whether the therapeutic effects of the combination of epratuzumab and rituximab are sufficiently promising to warrant evaluation in a subsequent randomized trial (in comparison to rituximab alone).

• To determine the relationship between the change in fludeoxyglucose F 18 uptake early after epratuzumab and rituximab treatment with response rate and time to progression.

OUTLINE:

• Induction therapy (month 1): Patients receive epratuzumab IV over 5-30 minutes on days 1, 8, 15, and 22 and rituximab IV on days 3, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity.

• Extended induction therapy (months 3, 5, 7, and 9): Patients receive epratuzumab IV over 5-30 minutes followed by rituximab IV in weeks 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity.

Patients receive fludeoxyglucose F 18 (FDG) subcutaneously and undergo positron emission tomography at baseline and after induction therapy to assess the degree of FDG uptake.

After completion of study treatment, patients are followed every 4 months for 2 years then every 6 months for up to 10 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Extended Induction Epratuzumab (Anti-CD22 Monoclonal Antibody) (CALGB IND #XXXXX) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin's Lymphoma (NHL)
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Epratuzumab Plus Rituximab Induction Therapy (Month 1): Epratuzumab 360 mg/m^2 by IV days 1, 8, 15 & 22; Rituximab 375 mg/m^2 by IV day 3, 8, 15 & 22 Extended Induction (Weeks 12, 20, 28 & 36) Epratuzumab 360 mg/m^2 by IV weeks 12, 20, 28 & 36; Rituximab 375 mg/m^2 by IV weeks 12, 20, 28 & 36	Biological: epratuzumab; Days 1, 8, 15, 22 and weeks 12, 20, 28, & 36: 360mg/sq m IV; Biological: rituximab; Day 3, 8, 15, 22 and weeks 12, 20, 28, & 36: 375mg/sq m IV

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Overall Response [12 months]

   Overall response is defined as achievement of a complete response (CR) or partial response (PR) as defined by the Revised Response Criteria for Malignant Lymphoma. CR: complete disappearance of all detectable disease PR: >=50% decrease in the sum of the product of diameters of indicator lesions

Secondary Outcome Measures

1. Progression Free Survival [Duration of study (up to 10 years)]

   Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically* confirmed follicular non-Hodgkin lymphoma (NHL)

• Previously untreated disease

• WHO classification grade 1, 2, or 3a (> 15 centroblasts per high power field with centrocytes present) that is stage III, IV, or bulky (i.e., single mass ≥ 7 cm in any unidimensional measurement) stage II disease NOTE: *Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine-needle aspirates are not acceptable for diagnosis

• Confirmed CD20 antigen expression by flow cytometry or immunohistochemistry

• Measurable disease by physical examination or imaging studies

• Any tumor mass > 1 cm is acceptable

• No nonmeasurable disease only, including any of the following:

• Bone lesions

• Ascites

• Pleural/pericardial effusion

• Lymphangitis cutis/pulmonis

• Bone marrow (involvement by NHL should be noted)

• No known CNS involvement by lymphoma

• Required to participate in companion FDG-PET imaging study CALGB 580701

PATIENT CHARACTERISTICS:

• ECOG performance status ≤ 2

• Absolute neutrophil count ≥ 1,000/μL

• Platelet count ≥ 50,000/μL

• Patients with HIV infection are eligible provided they meet the following criteria:

• No evidence of coinfection with hepatitis B or C

• CD4+ cell count ≥ 400/mm^3

• No evidence of resistant strains of HIV

• If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV RNA/mL

• If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL

• No history of AIDS-defining conditions

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for 3 months after completion of study therapy

• No known Human Anti-Chimeric Antibody (HACA)-positivity

PRIOR CONCURRENT THERAPY:

• No prior therapy for NHL including chemotherapy, radiotherapy, or immunotherapy (e.g., monoclonal antibody-based therapy)

• More than 2 weeks since prior corticosteroids except for maintenance therapy for non-malignant disease

• No concurrent dexamethasone or other steroids as antiemetics except for the following circumstances:

• Treatment of acute infusion reactions according to institutional procedures

• No concurrent hormonal therapy except steroids for adrenal failure OR hormones for non-disease-related conditions (e.g., insulin for diabetes)

• No other concurrent chemotherapeutic agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente Medical Office -Vandever Medical Office	San Diego	California	United States	92120
2	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
3	Middlesex Hospital Cancer Center	Middletown	Connecticut	United States	06457
4	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
5	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
6	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
7	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5001
8	University of Illinois Cancer Center	Chicago	Illinois	United States	60612-7243
9	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
10	Elkhart General Hospital	Elkhart	Indiana	United States	46515
11	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46845
12	Howard Community Hospital	Kokomo	Indiana	United States	46904
13	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
14	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
15	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
16	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
17	South Bend Clinic	South Bend	Indiana	United States	46617
18	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa	United States	52722
19	Union Hospital Cancer Program at Union Hospital	Elkton MD	Maryland	United States	21921
20	Dana-Farber/Brigham and Women's Cancer Center	Boston	Massachusetts	United States	02115
21	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
22	Oncology Care Associates, PLLC	Saint Joseph	Michigan	United States	49085
23	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
24	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
25	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
26	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care	Concord	New Hampshire	United States	03301
27	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire	United States	03106
28	Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
29	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
30	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
31	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
32	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
33	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
34	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
35	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
36	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
37	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio	United States	43210-1240
38	Mountainview Medical	Berlin	Vermont	United States	05602
39	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
40	Danville Regional Medical Center	Danville	Virginia	United States	24541
41	Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County	Martinsville	Virginia	United States	24115
42	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
43	St. Mary's Regional Cancer Center at St. Mary's Medical Center	Huntington	West Virginia	United States	25702

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Barbara Grant, MD, University of Vermont

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00553501
• Other Study ID Numbers: CALGB-50701; U10CA031946; CALGB-50701; CDR0000572604
• First Posted: Nov 4, 2007
• Last Update Posted: Jul 6, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Alliance for Clinical Trials in Oncology: stage II grade 1 follicular lymphoma; stage II grade 2 follicular lymphoma; stage II grade 3 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Rituximab; Epratuzumab

Study Results

Participant Flow

Recruitment Details	Between March 2008 and July 2009, 60 participants were recruited.
Pre-assignment Detail	One participant was deemed ineligible and excluded from all analyses per study design.

Arm/Group Title	Epratuzumab Plus Rituximab
Arm/Group Description	Induction Therapy (Month 1): Epratuzumab 360 mg/m^2 by IV days 1, 8, 15 & 22; Rituximab 375 mg/m^2 by IV day 3, 8, 15 & 22 Extended Induction (Weeks 12, 20, 28 & 36) Epratuzumab 360 mg/m^2 by IV weeks 12, 20, 28 & 36; Rituximab 375 mg/m^2 by IV weeks 12, 20, 28 & 36
Period Title: Overall Study
STARTED	59
COMPLETED	55
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Epratuzumab Plus Rituximab
Arm/Group Description	Induction Therapy (Month 1): Epratuzumab 360 mg/m^2 by IV days 1, 8, 15 & 22; Rituximab 375 mg/m^2 by IV day 3, 8, 15 & 22 Extended Induction (Weeks 12, 20, 28 & 36) Epratuzumab 360 mg/m^2 by IV weeks 12, 20, 28 & 36; Rituximab 375 mg/m^2 by IV weeks 12, 20, 28 & 36
Overall Participants	59
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54
Sex: Female, Male (Count of Participants)
Female	35 59.3%
Male	24 40.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 1.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 3.4%
White	54 91.5%
More than one race	0 0%
Unknown or Not Reported	2 3.4%
Region of Enrollment (participants) [Number]
United States	59 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Overall Response
Description	Overall response is defined as achievement of a complete response (CR) or partial response (PR) as defined by the Revised Response Criteria for Malignant Lymphoma. CR: complete disappearance of all detectable disease PR: >=50% decrease in the sum of the product of diameters of indicator lesions
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epratuzumab Plus Rituximab
Arm/Group Description	Induction Therapy (Month 1): Epratuzumab 360 mg/m^2 by IV days 1, 8, 15 & 22; Rituximab 375 mg/m^2 by IV day 3, 8, 15 & 22 Extended Induction (Weeks 12, 20, 28 & 36) Epratuzumab 360 mg/m^2 by IV weeks 12, 20, 28 & 36; Rituximab 375 mg/m^2 by IV weeks 12, 20, 28 & 36
Measure Participants	59
Complete Response	25 42.4%
Partial Response	27 45.8%

2. Secondary Outcome

Title	Progression Free Survival
Description	Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.
Time Frame	Duration of study (up to 10 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epratuzumab Plus Rituximab
Arm/Group Description	Induction Therapy (Month 1): Epratuzumab 360 mg/m^2 by IV days 1, 8, 15 & 22; Rituximab 375 mg/m^2 by IV day 3, 8, 15 & 22 Extended Induction (Weeks 12, 20, 28 & 36) Epratuzumab 360 mg/m^2 by IV weeks 12, 20, 28 & 36; Rituximab 375 mg/m^2 by IV weeks 12, 20, 28 & 36
Measure Participants	59
Median (95% Confidence Interval) [years]	3.5

3. Post-Hoc Outcome

Title	3-Year Overall Survival
Description	Percentage of participants who were alive at 3 years. The 3 year survival, with 95% confidence interval, was estimated using the Kaplan Meier method.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epratuzumab Plus Rituximab
Arm/Group Description	Induction Therapy (Month 1): Epratuzumab 360 mg/m^2 by IV days 1, 8, 15 & 22; Rituximab 375 mg/m^2 by IV day 3, 8, 15 & 22 Extended Induction (Weeks 12, 20, 28 & 36) Epratuzumab 360 mg/m^2 by IV weeks 12, 20, 28 & 36; Rituximab 375 mg/m^2 by IV weeks 12, 20, 28 & 36
Measure Participants	59
Number (95% Confidence Interval) [percentage of participants]	91 154.2%

Adverse Events

Arm/Group Title	Epratuzumab Plus Rituximab
Arm/Group Description	Induction Therapy (Month 1): Epratuzumab 360 mg/m^2 by IV days 1, 8, 15 & 22; Rituximab 375 mg/m^2 by IV day 3, 8, 15 & 22 Extended Induction (Weeks 12, 20, 28 & 36) Epratuzumab 360 mg/m^2 by IV weeks 12, 20, 28 & 36; Rituximab 375 mg/m^2 by IV weeks 12, 20, 28 & 36
All Cause Mortality
	Epratuzumab Plus Rituximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Epratuzumab Plus Rituximab
	Affected / at Risk (%)	# Events
Total	10/59 (16.9%)
Blood and lymphatic system disorders
Hemoglobin decreased	6/59 (10.2%)	7
Cardiac disorders
Atrial fibrillation	1/59 (1.7%)	1
Cardiac disorder	1/59 (1.7%)	1
Left ventricular failure	1/59 (1.7%)	1
Myocardial ischemia	2/59 (3.4%)	2
Gastrointestinal disorders
Abdominal pain	1/59 (1.7%)	2
Diarrhea	2/59 (3.4%)	3
Nausea	3/59 (5.1%)	4
Rectal hemorrhage	1/59 (1.7%)	1
Rectal pain	1/59 (1.7%)	1
Vomiting	1/59 (1.7%)	2
General disorders
Edema limbs	1/59 (1.7%)	1
Fatigue	8/59 (13.6%)	9
Fever	1/59 (1.7%)	1
Localized edema	1/59 (1.7%)	1
Pain	1/59 (1.7%)	1
Visceral edema	1/59 (1.7%)	1
Immune system disorders
Cytokine release syndrome	1/59 (1.7%)	1
Hypersensitivity	1/59 (1.7%)	1
Infections and infestations
Catheter related infection	1/59 (1.7%)	1
Endocarditis infective	1/59 (1.7%)	1
Infection	1/59 (1.7%)	1
Peripheral nerve infection	1/59 (1.7%)	1
Pneumonia	1/59 (1.7%)	1
Sepsis	1/59 (1.7%)	1
Investigations
Alanine aminotransferase increased	2/59 (3.4%)	2
Alkaline phosphatase increased	2/59 (3.4%)	2
Aspartate aminotransferase increased	3/59 (5.1%)	3
Blood bilirubin increased	2/59 (3.4%)	2
Cardiac troponin I increased	2/59 (3.4%)	2
Creatinine increased	2/59 (3.4%)	2
Laboratory test abnormal	1/59 (1.7%)	1
Lymphocyte count decreased	2/59 (3.4%)	2
Platelet count decreased	3/59 (5.1%)	3
Metabolism and nutrition disorders
Anorexia	1/59 (1.7%)	1
Blood glucose increased	5/59 (8.5%)	6
Blood uric acid increased	2/59 (3.4%)	2
Dehydration	1/59 (1.7%)	2
Serum albumin decreased	2/59 (3.4%)	2
Serum calcium decreased	2/59 (3.4%)	3
Serum glucose decreased	1/59 (1.7%)	2
Serum potassium decreased	1/59 (1.7%)	1
Serum potassium increased	1/59 (1.7%)	1
Serum sodium decreased	1/59 (1.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/59 (3.4%)	2
Muscle weakness	3/59 (5.1%)	4
Myalgia	1/59 (1.7%)	1
Nervous system disorders
Dizziness	1/59 (1.7%)	1
Headache	2/59 (3.4%)	2
Mini mental status examination abnormal	1/59 (1.7%)	1
Psychiatric disorders
Anxiety	1/59 (1.7%)	1
Renal and urinary disorders
Bladder hemorrhage	1/59 (1.7%)	1
Renal failure	1/59 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/59 (5.1%)	3
Dyspnea	3/59 (5.1%)	3
Hypoxia	1/59 (1.7%)	1
Respiratory disorder	1/59 (1.7%)	1
Skin and subcutaneous tissue disorders
Sweating	2/59 (3.4%)	2
Vascular disorders
Hot flashes	1/59 (1.7%)	1
Hypertension	1/59 (1.7%)	1
Hypotension	2/59 (3.4%)	2
Thrombosis	2/59 (3.4%)	2
Other (Not Including Serious) Adverse Events
	Epratuzumab Plus Rituximab
	Affected / at Risk (%)	# Events
Total	58/59 (98.3%)
Blood and lymphatic system disorders
Hemoglobin decreased	15/59 (25.4%)	37
Lymph node pain	7/59 (11.9%)	13
Cardiac disorders
Cardiac disorder	2/59 (3.4%)	2
Palpitations	1/59 (1.7%)	2
Sinus tachycardia	1/59 (1.7%)	1
Eye disorders
Dry eye syndrome	1/59 (1.7%)	3
Eye disorder	1/59 (1.7%)	2
Vision blurred	1/59 (1.7%)	1
Gastrointestinal disorders
Abdominal distension	3/59 (5.1%)	3
Abdominal pain	10/59 (16.9%)	14
Constipation	11/59 (18.6%)	21
Diarrhea	5/59 (8.5%)	10
Dry mouth	2/59 (3.4%)	4
Dyspepsia	5/59 (8.5%)	5
Dysphagia	1/59 (1.7%)	1
Ear, nose and throat examination abnormal	1/59 (1.7%)	1
Gastrointestinal disorder	3/59 (5.1%)	3
Gingival pain	1/59 (1.7%)	1
Nausea	21/59 (35.6%)	29
Stomach pain	1/59 (1.7%)	2
Vomiting	6/59 (10.2%)	8
General disorders
Chills	8/59 (13.6%)	8
Edema limbs	6/59 (10.2%)	10
Fatigue	35/59 (59.3%)	100
Fever	11/59 (18.6%)	15
Flu-like symptoms	1/59 (1.7%)	1
General symptom	1/59 (1.7%)	1
Pain	6/59 (10.2%)	9
Immune system disorders
Cytokine release syndrome	5/59 (8.5%)	9
Hypersensitivity	2/59 (3.4%)	4
Immune system disorder	1/59 (1.7%)	1
Infections and infestations
Bladder infection	1/59 (1.7%)	1
Bronchitis	2/59 (3.4%)	2
Catheter related infection	1/59 (1.7%)	1
Infection	1/59 (1.7%)	1
Otitis media	1/59 (1.7%)	1
Upper respiratory infection	6/59 (10.2%)	11
Urinary tract infection	3/59 (5.1%)	3
Vaginal infection	1/59 (1.7%)	1
Injury, poisoning and procedural complications
Fracture	1/59 (1.7%)	1
Wound dehiscence	1/59 (1.7%)	1
Investigations
Alanine aminotransferase increased	7/59 (11.9%)	19
Alkaline phosphatase increased	4/59 (6.8%)	12
Aspartate aminotransferase increased	11/59 (18.6%)	22
Blood bilirubin increased	13/59 (22%)	29
Creatinine increased	4/59 (6.8%)	15
Laboratory test abnormal	5/59 (8.5%)	12
Leukocyte count decreased	12/59 (20.3%)	28
Lymphocyte count decreased	10/59 (16.9%)	18
Neutrophil count decreased	6/59 (10.2%)	13
Platelet count decreased	12/59 (20.3%)	24
Weight loss	1/59 (1.7%)	2
Metabolism and nutrition disorders
Anorexia	2/59 (3.4%)	2
Blood glucose increased	22/59 (37.3%)	60
Blood uric acid increased	4/59 (6.8%)	6
Dehydration	2/59 (3.4%)	3
Serum albumin decreased	7/59 (11.9%)	11
Serum calcium decreased	7/59 (11.9%)	13
Serum calcium increased	2/59 (3.4%)	2
Serum glucose decreased	7/59 (11.9%)	11
Serum phosphate decreased	5/59 (8.5%)	12
Serum potassium decreased	9/59 (15.3%)	11
Serum potassium increased	9/59 (15.3%)	14
Serum sodium decreased	13/59 (22%)	20
Musculoskeletal and connective tissue disorders
Arthralgia	7/59 (11.9%)	20
Back pain	11/59 (18.6%)	16
Bone pain	2/59 (3.4%)	4
Chest wall pain	1/59 (1.7%)	1
Muscle weakness	1/59 (1.7%)	1
Muscle weakness upper limb	1/59 (1.7%)	1
Myalgia	6/59 (10.2%)	8
Neck pain	3/59 (5.1%)	7
Pain in extremity	2/59 (3.4%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	1/59 (1.7%)	1
Nervous system disorders
Dizziness	5/59 (8.5%)	6
Dysgeusia	2/59 (3.4%)	3
Extrapyramidal disorder	1/59 (1.7%)	1
Headache	9/59 (15.3%)	13
Memory impairment	1/59 (1.7%)	2
Neuralgia	1/59 (1.7%)	5
Neurological disorder NOS	1/59 (1.7%)	1
Peripheral sensory neuropathy	7/59 (11.9%)	11
Tremor	1/59 (1.7%)	1
Psychiatric disorders
Agitation	1/59 (1.7%)	1
Anxiety	6/59 (10.2%)	8
Depression	2/59 (3.4%)	2
Insomnia	8/59 (13.6%)	17
Libido decreased	1/59 (1.7%)	2
Renal and urinary disorders
Glomerular filtration rate decreased	1/59 (1.7%)	1
Urinary frequency	1/59 (1.7%)	2
Urine discoloration	1/59 (1.7%)	1
Urogenital disorder	4/59 (6.8%)	4
Reproductive system and breast disorders
Pelvic pain	1/59 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	6/59 (10.2%)	7
Cough	10/59 (16.9%)	12
Dyspnea	6/59 (10.2%)	9
Epistaxis	1/59 (1.7%)	1
Pharyngolaryngeal pain	1/59 (1.7%)	1
Respiratory disorder	3/59 (5.1%)	3
Skin and subcutaneous tissue disorders
Alopecia	1/59 (1.7%)	1
Dry skin	2/59 (3.4%)	2
Hand-and-foot syndrome	1/59 (1.7%)	3
Pruritus	11/59 (18.6%)	11
Rash desquamating	6/59 (10.2%)	7
Skin disorder	5/59 (8.5%)	6
Sweating	5/59 (8.5%)	8
Vascular disorders
Flushing	2/59 (3.4%)	3
Hot flashes	5/59 (8.5%)	10
Hypertension	4/59 (6.8%)	8
Hypotension	2/59 (3.4%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.