LBH589 in Relapsed or Relapsed and Refractory Waldenstrom's Macroglobulinemia

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00936611
• Collaborator: Brigham and Women's Hospital (Other), Novartis (Industry)
• Enrollment: 39
• Locations: 2
• Arm: 1
• Actual Duration (Months): 40
• Patients Per Site: 19.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this research study is to assess the overall response rate of LBH589 in patients with relapsed or refractory Waldenstrom's Macroglobulinemia. LBH589 is a newly discovered compound that has killed Waldenstrom cells in laboratory studies, however, it is not known if LBH589 will show the same activity in people with Waldenstrom's Macroglobulinemia. This drug has been used in research for the treatment of other types of cancer, such as multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Waldenstrom's Macroglobulinemia	Drug: LBH589	Phase 2

Detailed Description

This phase II study is designed to assess the toxicity profile and the proportion of overall response in patients with relapsed or refractory WM. This will study the effect of single agent LBH589 on response in these patients. Efficacy measures will include both objective clinical measurements and investigator-reported outcomes. Response and time to event analyses will follow the criteria set forth in the International Waldenstrom consortium recommendations. Prior to the start of the study, investigators will assess disease and perform a CT scan of the chest, abdomen and pelvis.

Response will be assessed after 2 cycles. If patients have stable disease or response, then they will continue on therapy until progression or unacceptable toxicity, being assessed every cycle until the sixth cycle and then every 3 months. Patients who show progression after 2 cycles will come off therapy and undergo event monitoring every 3 months. All responses will be assessed by M-protein quantification and immunofixation from serum and IgM monoclonal protein level. In addition, BM biopsies will be done at baseline, at the end of cycle 6 and at the end of all therapy. The protocol was amended because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of LBH589 (Panobinostat) in Relapsed or Relapsed and Refractory Waldenstrom's Macroglobulinemia
• Actual Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: LBH589 30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: 25 mg, 20 mg three times a week every week Or 20 mg three times a week every other week. No dose re-escalation was allowed. The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose.

Drug: LBH589; Other Names: panobinostat

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [Assessed after 2nd cycle and then every subsequent cycle for 6 cycles. The median number of completed cycles of therapy was 5 (0- 32). As such observed up to ~32 months.]

   Overall response rate is percentage of participants with complete (CR), very good partial (VGPR), partial (PR), or minimal response (MR) as best response during treatment. CR Disappearance of monoclonal protein by immunofixation No histologic evidence of bone marrow involvement Resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM. Second immunofixation required for confirmation. VGPR -At least 90% reduction of serum monoclonal IgM concentration on protein electrophoresis. PR At least 50% reduction of serum monoclonal IgM concentration on protein electrophoresis and at least 50% decrease in adenopathy/organomegaly on physical examination or on CT scan. No new symptoms or signs of active disease. MR At least 25% but less than 50% reduction of serum monoclonal IgM by protein electrophoresis. No new symptoms or signs of active disease.

Secondary Outcome Measures

1. Median Progression Free Survival [Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).]

   Progression free survival (PFS) is defined as the time from start of treatment to disease progression or death from any cause as estimated by Kaplan Meier methods. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free.

2. Median Time to Progression [Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).]

   Time to progression (TTP) is defined as the time from start of treatment to progression. Patients who have not progressed are censored at the date the patient is last known to be progression free.

3. Median Duration of Response [Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).]

   Duration of response DR is defined as the time from the date of first response after treatment to the date of disease progression Patients who have died for any cause or are alive without progression are censored at the date the patient is last know to be progression-free. Duration of response DR is defined as the time from the date of first response after treatment to the date of disease progression or death for any cause. Patients who are alive without progression are censored at the date the patient is last know to be progression-free.

4. Number of Participants With Grade 3 and 4 Treatment-Related Thrombocytopenia [Assessed after 2nd cycle, every subsequent cycle for 6 cycles and then every 3 months. Once off-treatment, adverse events will be assessed for 30 days. The median (range) number of completed cycles of therapy was 5 (0- 32). Therefore, up to ~33 months.]

   Grade 3 thrombocytopenia is defined as having 25,000-50,000 /uL platelets Grade 4 thrombocytopenia is defined as having < 25,000 /uL platelets

5. Acetylated Histone H3 and Overall Response Association [Bone marrow biopsies were obtained at the start of treatment (baseline) and after the 6th cycle.]

   Acetylated-histone-H3 levels were obtained through bone marrow biopsies and measured using established methods. This analysis aimed to analyze the association between overall response and percent change of acetylated histone h3 in samples using a paired t-test.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female patients aged 18 years or older

• Must have received prior therapy for their WM, any number of prior therapies is allowed

• Must have symptomatic relapsed or refractory WM

• Measurable monoclonal IgM protein in the blood and presence of lymphoplasmacytic cells in the bone marrow during any previous bone marrow

• Laboratory values as described in the protocol

• Clinically euthyroid

• ECOG Performance Status of 2 or less

Exclusion Criteria:

• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer

• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment

• Peripheral neuropathy CTCAE grade 2 or higher

• Impaired cardiac function or clinically significant cardiac diseases

• Impairment of GI function or GI disease that may significantly alter the absorption of LBH589

• Diarrhea > CTCAE grade 1

• Other concurrent severe and/or uncontrolled medical conditions including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol

• Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug

• Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies

• Patients who have received chemotherapy or rituximab within 3 weeks or less; or radiation therapy to > 30% of marrow-bearing bone within 2 weeks or less prior to starting study treatment; or who have not yet recovered from side effects of such therapies

• Patients who have received corticosteroids 2 weeks or less prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than than Waldenstrom's Macroglobulinemia

• Patients with active bleeding tendency or receiving any treatment with therapeutic doses of sodium warfarin or coumadin derivatives. Low doses of Coumadin to maintain line patency is allowed

• Patients who have undergone major surgery 4 weeks or less prior to starting study drug or who have not recovered from side effects of such therapy

• Women who are pregnant or breast feeding or women of childbearing potential not using an effective method of birth control

• Male patients whose sexual partners are women of childbearing potential not using effective methods of birth control

• Patients with prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)

• Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required

• Patients with a significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80220
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Brigham and Women's Hospital
• Novartis

Investigators

• Principal Investigator: Irene Ghobrial, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 25, 2019

More Information

Publications

None provided.

• Responsible Party: Irene Ghobrial, MD, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00936611
• Other Study ID Numbers: 09-071; CLBH589CUS56T
• First Posted: Jul 10, 2009
• Last Update Posted: Jan 28, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Irene Ghobrial, MD, Principal Investigator, Dana-Farber Cancer Institute: LBH589; WM; panobinostat; relapsed; waldenstrom; macroglobulinemia
• Additional relevant MeSH terms: Waldenstrom Macroglobulinemia; Panobinostat

Study Results

Participant Flow

Recruitment Details	From July 2009 to March 2011

Arm/Group Title	LBH589
Arm/Group Description	30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: 25 mg, 20 mg three times a week every week Or 20 mg three times a week every other week. No dose re-escalation was allowed. The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose. LBH589
Period Title: Overall Study
STARTED	39
Treated	36
Starting Dose Reduction: 30 mg to 25 mg	12
COMPLETED	0
NOT COMPLETED	39

Baseline Characteristics

Arm/Group Title	LBH589
Arm/Group Description	30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: 25 mg, 20 mg three times a week every week Or 20 mg three times a week every other week. No dose re-escalation was allowed. The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose. LBH589
Overall Participants	36
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61.6
Sex: Female, Male (Count of Participants)
Female	22 61.1%
Male	14 38.9%
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	0 0%
White	35 97.2%
More than one race	0 0%
Unknown or Not Reported	1 2.8%
Median IgM (mg/dL) [Median (Full Range) ]
Median (Full Range) [mg/dL]	3240
Median M Spike (gm/dL) [Median (Full Range) ]
Median (Full Range) [gm/dL]	2.06
Median Platelets (platelets x 10^3 / mL) [Median (Full Range) ]
Median (Full Range) [platelets x 10^3 / mL]	242
Median Hemoglobin (gm/dL) [Median (Full Range) ]
Median (Full Range) [gm/dL]	10.7
Median Beta 2 Microglobulin (mg/dL) [Median (Full Range) ]
Median (Full Range) [mg/dL]	3.3
Percentage of Bone Marrow Involvement (percentage of marrow) [Median (Full Range) ]
Median (Full Range) [percentage of marrow]	70
Lymph Nodes and Hepatocyte Selection Medium Assessment by CT Scan Evidence of Disease (Count of Participants)
Present	29 80.6%
Absent	7 19.4%
International Prognostic Scoring System for Waldenstrom Macroglobulinemia (Count of Participants)
High	7 19.4%
Intermediate	14 38.9%
Low	15 41.7%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	Overall response rate is percentage of participants with complete (CR), very good partial (VGPR), partial (PR), or minimal response (MR) as best response during treatment. CR Disappearance of monoclonal protein by immunofixation No histologic evidence of bone marrow involvement Resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM. Second immunofixation required for confirmation. VGPR -At least 90% reduction of serum monoclonal IgM concentration on protein electrophoresis. PR At least 50% reduction of serum monoclonal IgM concentration on protein electrophoresis and at least 50% decrease in adenopathy/organomegaly on physical examination or on CT scan. No new symptoms or signs of active disease. MR At least 25% but less than 50% reduction of serum monoclonal IgM by protein electrophoresis. No new symptoms or signs of active disease.
Time Frame	Assessed after 2nd cycle and then every subsequent cycle for 6 cycles. The median number of completed cycles of therapy was 5 (0- 32). As such observed up to ~32 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LBH589
Arm/Group Description	30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: 25 mg, 20 mg three times a week every week Or 20 mg three times a week every other week. No dose re-escalation was allowed. The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose. LBH589
Measure Participants	36
Number (90% Confidence Interval) [percentage of participants]	47 130.6%

2. Secondary Outcome

Title	Median Progression Free Survival
Description	Progression free survival (PFS) is defined as the time from start of treatment to disease progression or death from any cause as estimated by Kaplan Meier methods. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free.
Time Frame	Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LBH589
Arm/Group Description	30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: 25 mg, 20 mg three times a week every week Or 20 mg three times a week every other week. No dose re-escalation was allowed. The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose. LBH589
Measure Participants	36
Median (90% Confidence Interval) [months]	6.6

3. Secondary Outcome

Title	Median Time to Progression
Description	Time to progression (TTP) is defined as the time from start of treatment to progression. Patients who have not progressed are censored at the date the patient is last known to be progression free.
Time Frame	Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LBH589
Arm/Group Description	30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: 25 mg, 20 mg three times a week every week Or 20 mg three times a week every other week. No dose re-escalation was allowed. The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose. LBH589
Measure Participants	36
Median (90% Confidence Interval) [months]	6.6

4. Secondary Outcome

Title	Median Duration of Response
Description	Duration of response DR is defined as the time from the date of first response after treatment to the date of disease progression Patients who have died for any cause or are alive without progression are censored at the date the patient is last know to be progression-free. Duration of response DR is defined as the time from the date of first response after treatment to the date of disease progression or death for any cause. Patients who are alive without progression are censored at the date the patient is last know to be progression-free.
Time Frame	Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LBH589
Arm/Group Description	30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: 25 mg, 20 mg three times a week every week Or 20 mg three times a week every other week. No dose re-escalation was allowed. The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose. LBH589
Measure Participants	36
Median (90% Confidence Interval) [months]	6.9

5. Secondary Outcome

Title	Number of Participants With Grade 3 and 4 Treatment-Related Thrombocytopenia
Description	Grade 3 thrombocytopenia is defined as having 25,000-50,000 /uL platelets Grade 4 thrombocytopenia is defined as having < 25,000 /uL platelets
Time Frame	Assessed after 2nd cycle, every subsequent cycle for 6 cycles and then every 3 months. Once off-treatment, adverse events will be assessed for 30 days. The median (range) number of completed cycles of therapy was 5 (0- 32). Therefore, up to ~33 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LBH589
Arm/Group Description	30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: 25 mg, 20 mg three times a week every week Or 20 mg three times a week every other week. No dose re-escalation was allowed. The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose. LBH589
Measure Participants	36
Number [participants]	24 66.7%

6. Secondary Outcome

Title	Acetylated Histone H3 and Overall Response Association
Description	Acetylated-histone-H3 levels were obtained through bone marrow biopsies and measured using established methods. This analysis aimed to analyze the association between overall response and percent change of acetylated histone h3 in samples using a paired t-test.
Time Frame	Bone marrow biopsies were obtained at the start of treatment (baseline) and after the 6th cycle.

Outcome Measure Data

Analysis Population Description

Only three complete sample (baseline and post-therapy) were ascertained. The difference in percentage of acetylated histone h3 were not large enough to conduct the correlative analysis.

Arm/Group Title	LBH589
Arm/Group Description	30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: 25 mg, 20 mg three times a week every week Or 20 mg three times a week every other week. No dose re-escalation was allowed. The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose. LBH589
Measure Participants	0

Adverse Events

Time Frame	Assessed after 2nd cycle, every subsequent cycle for 6 cycles and then every 3 months. Once off-treatment, adverse events will be assessed for 30 days. The median (range) number of completed cycles of therapy was 5 (0- 32). Therefore, up to ~33 months.
Adverse Event Reporting Description	Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Arm/Group Title	LBH589
Arm/Group Description	30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: 25 mg, 20 mg three times a week every week Or 20 mg three times a week every other week. No dose re-escalation was allowed. The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose. LBH589
All Cause Mortality
	LBH589
	Affected / at Risk (%)	# Events
Total	28/39 (71.8%)
Serious Adverse Events
	LBH589
	Affected / at Risk (%)	# Events
Total	29/39 (74.4%)
Blood and lymphatic system disorders
Hemoglobin	10/39 (25.6%)
Gastrointestinal disorders
Diarrhea w/o prior colostomy	1/39 (2.6%)
Nausea	2/39 (5.1%)
Lower GI, hemorrhage NOS	1/39 (2.6%)
General disorders
Fatigue	5/39 (12.8%)
Infections and infestations
Infection w/ unk ANC lung	1/39 (2.6%)
Investigations
Leukocytes	7/39 (17.9%)
Neutrophils	13/39 (33.3%)
Platelets	23/39 (59%)
Bilirubin	1/39 (2.6%)
Metabolism and nutrition disorders
Hypophosphatemia	1/39 (2.6%)
Musculoskeletal and connective tissue disorders
Nonneuropathic generalized weakness	1/39 (2.6%)
Nervous system disorders
Syncope	2/39 (5.1%)
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory-other	1/39 (2.6%)
Other (Not Including Serious) Adverse Events
	LBH589
	Affected / at Risk (%)	# Events
Total	36/39 (92.3%)
Blood and lymphatic system disorders
Hemoglobin	14/39 (35.9%)
Lymph node, pain	2/39 (5.1%)
Cardiac disorders
Palpitations	4/39 (10.3%)
Sinus tachycardia	2/39 (5.1%)
Cardiac-other	1/39 (2.6%)
Ear and labyrinth disorders
Hearing w/w-o audiogr in monitor prg	1/39 (2.6%)
Otitis, external ear (non-infectious)	1/39 (2.6%)
Middle ear, pain	3/39 (7.7%)
Eye disorders
Dry eye syndrome	1/39 (2.6%)
Vision-blurred	3/39 (7.7%)
Tearing	1/39 (2.6%)
Ocular-other	1/39 (2.6%)
Eye, pain	1/39 (2.6%)
Gastrointestinal disorders
Colitis	1/39 (2.6%)
Constipation	6/39 (15.4%)
Periodontal disease	1/39 (2.6%)
Diarrhea w/o prior colostomy	21/39 (53.8%)
Dry mouth	4/39 (10.3%)
Dysphagia	1/39 (2.6%)
Esophagitis	2/39 (5.1%)
Flatulence	1/39 (2.6%)
Gastritis	4/39 (10.3%)
Dyspepsia	4/39 (10.3%)
Muco/stomatitis by exam, oral cavity	3/39 (7.7%)
Muco/stomatitis (symptom) oral cavity	1/39 (2.6%)
Nausea	16/39 (41%)
Vomiting	6/39 (15.4%)
GI-other	2/39 (5.1%)
Lower GI, hemorrhage NOS	1/39 (2.6%)
Abdomen, pain	7/39 (17.9%)
Anus, pain	1/39 (2.6%)
Stomach, pain	3/39 (7.7%)
General disorders
Fatigue	28/39 (71.8%)
Fever w/o neutropenia	4/39 (10.3%)
Rigors/chills	2/39 (5.1%)
Edema limb	8/39 (20.5%)
Chest/thoracic pain NOS	4/39 (10.3%)
Flu-like syndrome	1/39 (2.6%)
Immune system disorders
Allergy-other	1/39 (2.6%)
Infections and infestations
Infection w/ gr3-4 neut, upper airway	1/39 (2.6%)
Infection Gr0-2 neut, dental-tooth	1/39 (2.6%)
Infection Gr0-2 neut, sinus	2/39 (5.1%)
Infection Gr0-2 neut, upper airway	1/39 (2.6%)
Infection Gr0-2 neut, urinary tract	1/39 (2.6%)
Infection w/ unk ANC middle ear	1/39 (2.6%)
Infection w/ gr3-4 neut, skin	1/39 (2.6%)
Infection Gr0-2 neut, lung	1/39 (2.6%)
Infection Gr0-2 neut, sinus	1/39 (2.6%)
Infection-other	3/39 (7.7%)
Injury, poisoning and procedural complications
Intra-op injury Other (Specify)	1/39 (2.6%)
Bruising	3/39 (7.7%)
Investigations
Leukocytes	18/39 (46.2%)
Neutrophils	21/39 (53.8%)
Platelets	16/39 (41%)
Weight loss	8/39 (20.5%)
Bilirubin	1/39 (2.6%)
Creatinine	5/39 (12.8%)
Metabolism and nutrition disorders
Pancreatic glucose intolerance	1/39 (2.6%)
Anorexia	16/39 (41%)
Dehydration	2/39 (5.1%)
Hypoalbuminemia	5/39 (12.8%)
Hypocalcemia	1/39 (2.6%)
Hyperglycemia	6/39 (15.4%)
Hypoglycemia	2/39 (5.1%)
Hypophosphatemia	3/39 (7.7%)
Musculoskeletal and connective tissue disorders
Arthritis	1/39 (2.6%)
Nonneuropathic lower extr muscle weak	1/39 (2.6%)
Nonneuropathic generalized weakness	2/39 (5.1%)
Musculoskeletal/soft tissue-other	1/39 (2.6%)
Back, pain	2/39 (5.1%)
Extremity-limb, pain	5/39 (12.8%)
Joint, pain	1/39 (2.6%)
Muscle, pain	3/39 (7.7%)
Neck, pain	3/39 (7.7%)
Nervous system disorders
Taste disturbance	11/39 (28.2%)
Cognitive disturbance	2/39 (5.1%)
Dizziness	7/39 (17.9%)
Neuropathy-sensory	5/39 (12.8%)
Tremor	2/39 (5.1%)
Neurologic-other	1/39 (2.6%)
Head/headache	6/39 (15.4%)
Sinus, pain	1/39 (2.6%)
Psychiatric disorders
Confusion	2/39 (5.1%)
Anxiety	1/39 (2.6%)
Depression	1/39 (2.6%)
Renal and urinary disorders
Urethra, pain	1/39 (2.6%)
Obstruction-ureteral	1/39 (2.6%)
Urinary frequency/urgency	3/39 (7.7%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/39 (2.6%)
Nose, hemorrhage	5/39 (12.8%)
Cough	5/39 (12.8%)
Dyspnea	7/39 (17.9%)
Pneumonitis/pulmonary infiltrates	5/39 (12.8%)
Skin and subcutaneous tissue disorders
Sweating	1/39 (2.6%)
Dry skin	2/39 (5.1%)
Alopecia	6/39 (15.4%)
Nail changes	4/39 (10.3%)
Pruritus/itching	1/39 (2.6%)
Rash/desquamation	1/39 (2.6%)
Skin-other	2/39 (5.1%)
Petechiae	2/39 (5.1%)

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.