Study of Single Agent Lenalidomide in Older Adults With Newly Diagnosed Multiple Myeloma

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01054144
• Collaborator: Celgene (Industry)
• Enrollment: 27
• Location: 1
• Arm: 1
• Actual Duration (Months): 130.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research is to estimate the effectiveness of a response adapted approach with the use of the drug, lenalidomide in the treatment of older adults with newly diagnosed standard risk multiple myeloma. This means that participants will be given the study drug, lenalidomide but depending on how they respond to this drug they may also be given dexamethasone and/or prednisone to help with their treatment.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Lenalidomide; Drug: Prednisone; Drug: Dexamethasone	Phase 2

Detailed Description

Summary: Patients will be started on the study drug, lenalidomide on Day 1, Cycle 1. Lenalidomide is a capsule that is to be taken orally (by mouth). If the patient's disease progresses after 2 cycles of therapy, a low dose of dexamethasone will be added. If the patient's disease is stable after 2 cycles of therapy, the use of an alternate corticosteroid (prednisone) will be added to the lenalidomide therapy they are receiving. Dexamethasone and prednisone are in tablet form and will be taken orally (by mouth). However, if the patient has a minimal response after an additional 2 cycles of lenalidomide therapy, the therapy will be continued until their disease progresses. See the intervention descriptions for further details.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Response Adapted Therapy Using Single Agent Lenalidomide in Older Adults With Newly Diagnosed, Standard Risk Multiple Myeloma
• Actual Study Start Date: Jan 14, 2010
• Actual Primary Completion Date: Aug 1, 2020
• Actual Study Completion Date: Nov 24, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Response Adapted Therapy Lenalidomide, prednisone and dexamethasone as outlined in Intervention Descriptions.

Drug: Lenalidomide; Starting Dose: 25 mg by mouth (PO) days 1-21 of a 28 days cycle; Dose Level -1: 15 mg PO days 1-21 of a 28 days cycle; Dose Level -2: 10 mg PO days 1-21 of a 28 days cycle; Dose Level -3: 5 mg PO days 1-21 of a 28 days cycle; Dose Level -4: Discontinue; Other Names: Revlimid® ; Drug: Prednisone; Starting Dose: 100 mg PO days 1-5 every 28 days; Dose level -1: 50 mg PO days 1-5 of a 28 day cycle; Dose level -2: 25 mg PO days 1-5 of a 28 day cycle; Dose level -3: Discontinue; Drug: Dexamethasone; Starting Dose: 40 mg daily on days 1 - 4 every 28 days; Dose level -1: 20 mg daily on days 1 - 4 every 28 days; Dose level -1a: 40 mg daily on days 1, 2, and 3 followed by 20 mg on day 4 followed by 12 mg on day 5 followed by 8 mg on day 6; Dose level -2: 10 mg daily on days 1 - 4 every 28 days; Dose level -3: Discontinue; Other Names: Decadron

Outcome Measures

Primary Outcome Measures

1. Combined Therapy - Median Progression Free Survival [up to 36 months]

   Progression free survival (PFS) of older adults with mildly symptomatic multiple myeloma treated on this response adapted approach (i.e. time from start of lenalidomide to failure of lenalidomide and low dose dexamethasone)

Secondary Outcome Measures

1. Response Rate [Every 8 weeks up to 12 months]

   Response rate in older adults with mildly symptomatic multiple myeloma to single agent lenalidomide, lenalidomide prednisone and lenalidomide low dose dexamethasone in patients with suboptimal responses to lenalidomide monotherapy. The study used the uniform response assessment of the International Myeloma Working Group with the addition of MR (minimal response) (Durie et al, 2006; Kumar et al, 2016). MR was defined as a 25-49% decrease in serum M spike, and a 50-89% improvement in urine M spike. For patients without a measurable serum or urine M spike, a 25-49% decrease in the difference between the involved and uninvolved free light chains was required. The response in this trial is defined as complete remission (CR), stringent complete remission (SRC), very good partial remission (VGPR) and partial remission (PR) and minimal response (MR).

2. Number of Participants With Serious Adverse Events [Day 1 through Off Study Date, an average of 48 months]

   Number of participants with serious adverse events

3. Single Agent - Median Progressive Free Survival (PFS) [First measure at 8 weeks]

   The progression free survival of patients treated with single agent lenalidomide

4. Number of Participants With 1 Year Overall Survival (OS) [1 Year]

   The 1 year overall survival of older adults with mildly symptomatic multiple myeloma treated on this response adapted approach

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Understand and voluntarily sign an informed consent form

• Age ≥65 years or not eligible for high dose therapy and autologous stem cell transplant

• Able to adhere to study visit schedule and other protocol requirements

• Diagnosed with multiple myeloma and considered to have active disease. Patients must not have received an active chemotherapy regimen or Dexamethasone. Patients may have received palliative radiotherapy at least 2 weeks prior to the study start.

• Measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL), urine (≥ 0.2 g excreted in a 24-hour urine collection sample) or by serum free light chains (involved free light chain greater than 100mg/L)

• Eastern Cooperative Group (ECOG) Performance Status of 0 or 1

• Serum bilirubin levels ≤1.5 times the upper limit of the normal (ULN) range for the laboratory

• Serum aspartate transaminase (AST) or serum alanine transaminase (ALT) levels ≤2 x ULN

• Adequate bone marrow function: Absolute neutrophil count ≥ 1,000 cells/mm³ (1.0 x 10^9/L); Platelets ≥ 100,000 /mm³

• Hemoglobin > 8 g/dL

• Adequate renal function: Calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula

• Low risk myeloma is defined as the absence of the following adverse features[21]: t(4;14) by FISH or metaphase cytogenetics; t(14,16) or t(14;20) by FISH or metaphase cytogenetics; Deletion 17q13 by FISH; Deletion 13 by metaphase analysis; Aneuploidy by metaphase analysis; Β2 microglobulin > 5.5.

• Able to tolerate one of the following thromboprophylactic strategies: aspirin, low molecular weight heparin or warfarin (coumadin)

• Must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-international units per milliliter (mIU/mL) within 10 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy.

Exclusion Criteria:

• Ongoing severe infection requiring intravenous antibiotic treatment

• Life expectancy of less than 3 months

• Performance status of 2, 3 or 4

• Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the patient has been disease-free for at least 2 years

• Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia

• Uncontrolled medical problems such as diabetes mellitus, congestive heart failure, coronary artery disease, hypertension, unstable angina, arrhythmias), pulmonary, hepatic and renal diseases unless renal insufficiency is felt to be secondary to multiple myeloma.

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form

• Pregnant or lactating

• Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

• Known hypersensitivity to thalidomide

• Use of any other experimental drug or therapy within 28 days of baseline.

• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs

• Any prior use of lenalidomide

• Concurrent use of other anti-cancer agents or treatments

• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute
• Celgene

Investigators

• Principal Investigator: Rachid Baz, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 15, 2016

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT01054144
• Other Study ID Numbers: MCC-16018; 108562; RV-MM-PI-0454
• First Posted: Jan 22, 2010
• Last Update Posted: Oct 13, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: Newly Diagnosed Standard Risk Multiple Myeloma; Senior Adults
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Prednisone; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Response Adapted Therapy
Arm/Group Description	Lenalidomide, prednisone and dexamethasone as outlined in Intervention Descriptions. Lenalidomide: - Starting Dose: 25 mg by mouth (PO) days 1-21 of a 28 days cycle; Dose Level -1: 15 mg PO days 1-21 of a 28 days cycle; Dose Level -2: 10 mg PO days 1-21 of a 28 days cycle; Dose Level -3: 5 mg PO days 1-21 of a 28 days cycle; Dose Level -4: Discontinue Prednisone: - Starting Dose: 100 mg PO days 1-5 every 28 days; Dose level -1: 50 mg PO days 1-5 of a 28 day cycle; Dose level -2: 25 mg PO days 1-5 of a 28 day cycle; Dose level -3: Discontinue Dexamethasone: - Starting Dose: 40 mg daily on days 1 - 4 every 28 days; Dose level -1: 20 mg daily on days 1 - 4 every 28 days; Dose level -1a: 40 mg daily on days 1, 2, and 3 followed by 20 mg on day 4 followed by 12 mg on day 5 followed by 8 mg on day 6; Dose level -2: 10 mg daily on days 1 - 4 every 28 days; Dose level -3: Discontinue
Period Title: Overall Study
STARTED	27
COMPLETED	25
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Response Adapted Therapy
Arm/Group Description	Lenalidomide, prednisone and dexamethasone as outlined in Intervention Descriptions. Lenalidomide: - Starting Dose: 25 mg by mouth (PO) days 1-21 of a 28 days cycle; Dose Level -1: 15 mg PO days 1-21 of a 28 days cycle; Dose Level -2: 10 mg PO days 1-21 of a 28 days cycle; Dose Level -3: 5 mg PO days 1-21 of a 28 days cycle; Dose Level -4: Discontinue Prednisone: - Starting Dose: 100 mg PO days 1-5 every 28 days; Dose level -1: 50 mg PO days 1-5 of a 28 day cycle; Dose level -2: 25 mg PO days 1-5 of a 28 day cycle; Dose level -3: Discontinue Dexamethasone: - Starting Dose: 40 mg daily on days 1 - 4 every 28 days; Dose level -1: 20 mg daily on days 1 - 4 every 28 days; Dose level -1a: 40 mg daily on days 1, 2, and 3 followed by 20 mg on day 4 followed by 12 mg on day 5 followed by 8 mg on day 6; Dose level -2: 10 mg daily on days 1 - 4 every 28 days; Dose level -3: Discontinue
Overall Participants	27
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	27 100%
Sex: Female, Male (Count of Participants)
Female	11 40.7%
Male	16 59.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 7.4%
Not Hispanic or Latino	25 92.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 7.4%
White	25 92.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	27 100%

Outcome Measures

1. Primary Outcome

Title	Combined Therapy - Median Progression Free Survival
Description	Progression free survival (PFS) of older adults with mildly symptomatic multiple myeloma treated on this response adapted approach (i.e. time from start of lenalidomide to failure of lenalidomide and low dose dexamethasone)
Time Frame	up to 36 months

Outcome Measure Data

Analysis Population Description

Number of participants who received response adaptive therapy

Arm/Group Title	Response Adapted Therapy
Arm/Group Description	Lenalidomide, prednisone and dexamethasone as outlined in Intervention Descriptions. Lenalidomide: - Starting Dose: 25 mg by mouth (PO) days 1-21 of a 28 days cycle; Dose Level -1: 15 mg PO days 1-21 of a 28 days cycle; Dose Level -2: 10 mg PO days 1-21 of a 28 days cycle; Dose Level -3: 5 mg PO days 1-21 of a 28 days cycle; Dose Level -4: Discontinue Prednisone: - Starting Dose: 100 mg PO days 1-5 every 28 days; Dose level -1: 50 mg PO days 1-5 of a 28 day cycle; Dose level -2: 25 mg PO days 1-5 of a 28 day cycle; Dose level -3: Discontinue Dexamethasone: - Starting Dose: 40 mg daily on days 1 - 4 every 28 days; Dose level -1: 20 mg daily on days 1 - 4 every 28 days; Dose level -1a: 40 mg daily on days 1, 2, and 3 followed by 20 mg on day 4 followed by 12 mg on day 5 followed by 8 mg on day 6; Dose level -2: 10 mg daily on days 1 - 4 every 28 days; Dose level -3: Discontinue
Measure Participants	9
Median (95% Confidence Interval) [months]	36

2. Secondary Outcome

Title	Response Rate
Description	Response rate in older adults with mildly symptomatic multiple myeloma to single agent lenalidomide, lenalidomide prednisone and lenalidomide low dose dexamethasone in patients with suboptimal responses to lenalidomide monotherapy. The study used the uniform response assessment of the International Myeloma Working Group with the addition of MR (minimal response) (Durie et al, 2006; Kumar et al, 2016). MR was defined as a 25-49% decrease in serum M spike, and a 50-89% improvement in urine M spike. For patients without a measurable serum or urine M spike, a 25-49% decrease in the difference between the involved and uninvolved free light chains was required. The response in this trial is defined as complete remission (CR), stringent complete remission (SRC), very good partial remission (VGPR) and partial remission (PR) and minimal response (MR).
Time Frame	Every 8 weeks up to 12 months

Outcome Measure Data

Analysis Population Description

1 participant could not be evaluated for response.

Arm/Group Title	Response Adapted Therapy	Single Agent Lenalidomide
Arm/Group Description	Lenalidomide, prednisone and dexamethasone as outlined in Intervention Descriptions.	Participants treated with single agent lenalidomide
Measure Participants	9	26
Complete Response & Stringent Complete Response	1 3.7%	4 NaN
Very Good Partial Response (VGPR)	1 3.7%	3 NaN
Partial Response (PR)	2 7.4%	12 NaN
Minimal Response (MR)	5 18.5%	4 NaN
Stable Disease	0 0%	3 NaN
Overall Response >/= PR	4 14.8%	19 NaN

3. Secondary Outcome

Title	Number of Participants With Serious Adverse Events
Description	Number of participants with serious adverse events
Time Frame	Day 1 through Off Study Date, an average of 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Response Adapted Therapy
Arm/Group Description	Lenalidomide, prednisone and dexamethasone as outlined in Intervention Descriptions. Lenalidomide: - Starting Dose: 25 mg by mouth (PO) days 1-21 of a 28 days cycle; Dose Level -1: 15 mg PO days 1-21 of a 28 days cycle; Dose Level -2: 10 mg PO days 1-21 of a 28 days cycle; Dose Level -3: 5 mg PO days 1-21 of a 28 days cycle; Dose Level -4: Discontinue Prednisone: - Starting Dose: 100 mg PO days 1-5 every 28 days; Dose level -1: 50 mg PO days 1-5 of a 28 day cycle; Dose level -2: 25 mg PO days 1-5 of a 28 day cycle; Dose level -3: Discontinue Dexamethasone: - Starting Dose: 40 mg daily on days 1 - 4 every 28 days; Dose level -1: 20 mg daily on days 1 - 4 every 28 days; Dose level -1a: 40 mg daily on days 1, 2, and 3 followed by 20 mg on day 4 followed by 12 mg on day 5 followed by 8 mg on day 6; Dose level -2: 10 mg daily on days 1 - 4 every 28 days; Dose level -3: Discontinue
Measure Participants	27
Number [participants]	20 74.1%

4. Secondary Outcome

Title	Single Agent - Median Progressive Free Survival (PFS)
Description	The progression free survival of patients treated with single agent lenalidomide
Time Frame	First measure at 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Agent
Arm/Group Description	Participants who were treated with single agent lenalidomide only
Measure Participants	18
Median (95% Confidence Interval) [months]	29

5. Secondary Outcome

Title	Number of Participants With 1 Year Overall Survival (OS)
Description	The 1 year overall survival of older adults with mildly symptomatic multiple myeloma treated on this response adapted approach
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Response Adapted Therapy
Arm/Group Description	Lenalidomide, prednisone and dexamethasone as outlined in Intervention Descriptions. Lenalidomide: - Starting Dose: 25 mg by mouth (PO) days 1-21 of a 28 days cycle; Dose Level -1: 15 mg PO days 1-21 of a 28 days cycle; Dose Level -2: 10 mg PO days 1-21 of a 28 days cycle; Dose Level -3: 5 mg PO days 1-21 of a 28 days cycle; Dose Level -4: Discontinue Prednisone: - Starting Dose: 100 mg PO days 1-5 every 28 days; Dose level -1: 50 mg PO days 1-5 of a 28 day cycle; Dose level -2: 25 mg PO days 1-5 of a 28 day cycle; Dose level -3: Discontinue Dexamethasone: - Starting Dose: 40 mg daily on days 1 - 4 every 28 days; Dose level -1: 20 mg daily on days 1 - 4 every 28 days; Dose level -1a: 40 mg daily on days 1, 2, and 3 followed by 20 mg on day 4 followed by 12 mg on day 5 followed by 8 mg on day 6; Dose level -2: 10 mg daily on days 1 - 4 every 28 days; Dose level -3: Discontinue
Measure Participants	27
Number [participants]	27 100%

Adverse Events

Time Frame	Adverse Events collected from consent through off treatment date, an average of 24 months. Serious Adverse events collected from consent to off-study date, an average of 48 months
Arm/Group Title	All Participants
Arm/Group Description	All participants treated with Lenalidomide, prednisone and lenalidomide, prednisone and dexamethasone as outlined in Intervention Descriptions.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	2/27 (7.4%)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	20/27 (74.1%)
Cardiac disorders
General Cardiac Disorders - Other	3/27 (11.1%)	4
Hypertension	1/27 (3.7%)	2
Hypotension	2/27 (7.4%)	2
Gastrointestinal disorders
Dehydration	1/27 (3.7%)	1
Diarrhea	1/27 (3.7%)	1
Gastrointestinal disorders, other	1/27 (3.7%)	1
Colon Obstruction	1/27 (3.7%)	1
Hemorrhage, Stomach	1/27 (3.7%)	1
Cholecystitis	1/27 (3.7%)	1
General disorders
Coagulation	1/27 (3.7%)	1
General disorders - Other	1/27 (3.7%)	1
Fever	1/27 (3.7%)	2
Death	1/27 (3.7%)	1
Chest wall pain	1/27 (3.7%)	1
Limb pain	2/27 (7.4%)	2
Pain -Other	1/27 (3.7%)	1
Infections and infestations
Colitis, Infectious (e.g. Clostridium difficile)	2/27 (7.4%)	2
Febrile neutropenia	3/27 (11.1%)	3
Infection -Blood	2/27 (7.4%)	2
Infection - Lung	3/27 (11.1%)	3
Infection - Other	1/27 (3.7%)	2
Cellulitis	3/27 (11.1%)	3
Infection - Bladder	1/27 (3.7%)	1
Injury, poisoning and procedural complications
Fracture	1/27 (3.7%)	2
Investigations
Hypercalcemia	1/27 (3.7%)	1
Hyperglycemia	1/27 (3.7%)	1
Investigations -Other	1/27 (3.7%)	1
Hypokalemia	1/27 (3.7%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness	1/27 (3.7%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary malignancy	1/27 (3.7%)	1
Nervous system disorders
Confusion	1/27 (3.7%)	1
Syncope	1/27 (3.7%)	1
Psychiatric disorders
Mental status	1/27 (3.7%)	1
Renal and urinary disorders
Renal failure	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/27 (7.4%)	2
Skin and subcutaneous tissue disorders
Wound complication	1/27 (3.7%)	1
Vascular disorders
Hemorrhage, CNS	1/27 (3.7%)	1
Cerebrovascular ischemia	1/27 (3.7%)	1
Vascular -Other	1/27 (3.7%)	3
Non-myocardial vascular arterial ischemia	1/27 (3.7%)	1
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	27/27 (100%)
Blood and lymphatic system disorders
Neutrophils/granulocytes	25/27 (92.6%)	265
Leukopenia	22/27 (81.5%)	264
Low platelet count	20/27 (74.1%)	78
Hemoglobin, low	16/27 (59.3%)	75
Hemolysis	1/27 (3.7%)	1
Ear and labyrinth disorders
Pain - external ear	1/27 (3.7%)	1
Eye disorders
Pain - eye	1/27 (3.7%)	2
Gastrointestinal disorders
Constipation	24/27 (88.9%)	46
Diarrhea	23/27 (85.2%)	66
Nausea	17/27 (63%)	37
Gastrointestinal disorders - Other	12/27 (44.4%)	13
Vomiting	11/27 (40.7%)	14
Dehydration	9/27 (33.3%)	12
Heartburn/dyspepsia	7/27 (25.9%)	9
Distension/bloating, Abdominal	5/27 (18.5%)	6
Dysphagia	5/27 (18.5%)	5
Flatulence	2/27 (7.4%)	3
Dry mouth	2/27 (7.4%)	3
Mucositis/stomatitis - oral cavity	2/27 (7.4%)	2
Dysgeusia	2/27 (7.4%)	2
Enteritis	1/27 (3.7%)	1
Gastritis	1/27 (3.7%)	1
Hemorrhoids	1/27 (3.7%)	2
Obstruction, GI - Colon	1/27 (3.7%)	1
Abdominal Pain NOS	12/27 (44.4%)	18
Gallbladder pain	1/27 (3.7%)	1
General disorders
Fatigue	23/27 (85.2%)	63
Insomnia	13/27 (48.1%)	20
Fever (in absence of neutropenia)	10/27 (37%)	25
Rigors/chills	5/27 (18.5%)	7
Diaphoresis	4/27 (14.8%)	4
Constitutional symptoms - Other	3/27 (11.1%)	3
Back pain	21/27 (77.8%)	45
Pain - extremity/limb	16/27 (59.3%)	29
Headache	16/27 (59.3%)	26
Joint pain	10/27 (37%)	12
Chest wall pain	6/27 (22.2%)	7
Chest/thorax pain	5/27 (18.5%)	7
Neck pain	5/27 (18.5%)	7
Pain-throat/pharynx/larynx	5/27 (18.5%)	6
Pain - stomach	4/27 (14.8%)	4
Pain - NOS	3/27 (11.1%)	3
Bone pain	2/27 (7.4%)	3
Pain - lymph node	2/27 (7.4%)	2
Pain - oral, gum	2/27 (7.4%)	4
Breast pain	1/27 (3.7%)	1
Buttock pain	1/27 (3.7%)	1
Pain - dental	1/27 (3.7%)	1
Pain - face	1/27 (3.7%)	1
Oral cavity pain	1/27 (3.7%)	1
Pelvic pain	1/27 (3.7%)	1
Sinus pain	1/27 (3.7%)	1
Pain - testicle	1/27 (3.7%)	1
Edema - limb	21/27 (77.8%)	52
Edema -head and neck	3/27 (11.1%)	4
Edema - trunk	1/27 (3.7%)	1
Gait changes	5/27 (18.5%)	8
Gingivitus	2/27 (7.4%)	2
Infections and infestations
Febrile neutropenia	6/27 (22.2%)	7
Cellulitis	9/27 (33.3%)	11
Infection -Other	4/27 (14.8%)	4
Urinary Tract Infection	4/27 (14.8%)	4
Bronchus infection	3/27 (11.1%)	3
Eye infection	2/27 (7.4%)	2
Pneumonia	3/27 (11.1%)	3
Sinus infection	3/27 (11.1%)	3
Upper airway infection	1/27 (3.7%)	1
Conjunctiva infection	2/27 (7.4%)	2
Peripheral nerve infection	1/27 (3.7%)	1
Nail infection	1/27 (3.7%)	1
wound infection	1/27 (3.7%)	1
Bladder infection	1/27 (3.7%)	1
Colon infection	1/27 (3.7%)	1
Tooth infection	1/27 (3.7%)	1
Mucosal infection	1/27 (3.7%)	1
Investigations
Hyperglycemia	9/27 (33.3%)	13
Creatinine	7/27 (25.9%)	14
Hyperkalemia	7/27 (25.9%)	8
ALT, SGPT high	4/27 (14.8%)	6
Hyperbilirubinemia	4/27 (14.8%)	9
Hypoalbuminemia	3/27 (11.1%)	4
Alkaline phosphatase	3/27 (11.1%)	3
Hypokalemia	3/27 (11.1%)	5
Investigations - Other	11/27 (40.7%)	12
Hypercalcemia	2/27 (7.4%)	3
Hypocalcemia	2/27 (7.4%)	5
Hypoglycemia	2/27 (7.4%)	2
AST, SGOT	1/27 (3.7%)	1
Hypomagnesemia	1/27 (3.7%)	1
Hypernatremia	1/27 (3.7%)	1
Metabolism and nutrition disorders
Anorexia	12/27 (44.4%)	27
Weight loss	8/27 (29.6%)	11
Weight gain	4/27 (14.8%)	4
Musculoskeletal and connective tissue disorders
Pain - muscle	3/27 (11.1%)	3
Musculoskeletal and connective tissue disorders - Other	12/27 (44.4%)	19
Muscle weakess, generalized	11/27 (40.7%)	12
Muscle weakness, extraocular	3/27 (11.1%)	3
Muscle weakness, lower extremities	3/27 (11.1%)	3
Fracture	3/27 (11.1%)	3
Muscle weakness, trunk	2/27 (7.4%)	2
Arthritis	2/27 (7.4%)	2
Myositis	1/27 (3.7%)	1
Nervous system disorders
Neuropathy, sensory	19/27 (70.4%)	38
Dizziness	15/27 (55.6%)	29
Nervous system disorders -Other	9/27 (33.3%)	15
Tremor	8/27 (29.6%)	16
Neuropathy, motor	5/27 (18.5%)	6
Confusion	2/27 (7.4%)	3
CNS cerebrovascular ischemia	1/27 (3.7%)	1
Memory impairment	1/27 (3.7%)	1
Neuropathy, cranial	1/27 (3.7%)	1
Speech impairment	1/27 (3.7%)	1
Syncope	1/27 (3.7%)	1
Psychiatric disorders
Depression	6/27 (22.2%)	9
Agitation/Iritability	6/27 (22.2%)	8
Anxiety	3/27 (11.1%)	6
Personality/Behavior changes	1/27 (3.7%)	1
Reproductive system and breast disorders
Cough	16/27 (59.3%)	28
Respiratory, thoracic and mediastinal disorders
Dyspnea	14/27 (51.9%)	25
Respirator, thoracic and mediastrinal disorders -Other	9/27 (33.3%)	14
Loss or alteration of voice	4/27 (14.8%)	5
Bronchospasm, wheezing	1/27 (3.7%)	1
Paranasal/sinus reaction	1/27 (3.7%)	1
Obstruction of airway	1/27 (3.7%)	1
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders -Other	14/27 (51.9%)	27
Rash/desquamation	14/27 (51.9%)	15
Dry skin	11/27 (40.7%)	18
Pruritus/itching	10/27 (37%)	18
Rash, erythema multiforme	10/27 (37%)	16
Brusing	9/27 (33.3%)	13
Hyperpigmentation	2/27 (7.4%)	2
Nail changes	2/27 (7.4%)	3
Rash, acne/acneiform	2/27 (7.4%)	2
Wound complication, non-infectious	2/27 (7.4%)	3
Rash	1/27 (3.7%)	1
Skin breakdown/decubitus ulcer	1/27 (3.7%)	1
Urticaria	1/27 (3.7%)	1
Vascular disorders
Flushing	5/27 (18.5%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.