S0115, High-Dose Melphalan and Autologous Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma or Primary Systemic Amyloidosis

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00064337
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 104
• Locations: 35
• Arm: 1
• Duration (Months): 142
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy such as melphalan work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with donor peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving melphalan together with autologous stem cell transplantation works in treating patients with multiple myeloma or primary systemic amyloidosis.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma; Plasma Cell Myeloma	Biological: filgrastim; Drug: cyclophosphamide; Drug: dexamethasone; Drug: melphalan; Drug: thalidomide; Procedure: peripheral blood stem cell transplantation	Phase 2

Detailed Description

OBJECTIVES:

• Determine overall survival of patients with high-risk multiple myeloma, primary systemic amyloidosis, or light chain deposition disease treated with two courses of modified high-dose melphalan and autologous peripheral blood stem cell transplantation.

• Determine the hematologic response in patients treated with this regimen.

• Determine the qualitative and quantitative toxic effects of this regimen in these patients.

• Determine the prognostic significance of cytogenetic markers in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (high-risk multiple myeloma vs primary systemic amyloidosis vs both).

• Induction therapy (multiple myeloma patients only): Patients receive oral dexamethasone on days 1-4, 9-12, and 17-20 and oral thalidomide daily on days 1-35. Treatment repeats every 35 days for 2 courses in the absence of disease progression or unacceptable toxicity.

• Mobilization and stem cell collection:

• Multiple myeloma patients: Within 28-35 days after completion of induction therapy, patients receive cyclophosphamide IV over 2-3 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 2 and continuing through the day before the last leukapheresis. Usage of mesna IV on day 1 (prior to and twice after cyclophosphamide administration is recommended).

• Primary systemic amyloidosis patients: Patients receive G-CSF SC daily beginning on day 1 and continuing through the day before the last leukapheresis.

All patients undergo leukapheresis for the collection of stem cells until the target number of CD34+ cells is reached.

• Conditioning regimen: Within 1-4 weeks after mobilization, patients receive modified high-dose melphalan IV over 20 minutes on day -2.

• Peripheral blood stem cell (PBSC) reinfusion: PBSCs are reinfused on day 0. Patients receive G-CSF SC daily beginning on day 1 and continuing until blood counts recover.

Patients undergo a second autologous PBSC transplantation within 3-6 months, but no later than 12 months, after the first transplantation.

• Second conditioning regimen: Patients receive modified high-dose melphalan IV over 20 minutes on day -2.

• Second PBSC infusion: PBSCs are infused on day 0.

• Maintenance regimen (multiple myeloma patients only): Between 4-8 weeks after the second transplantation, patients with no progressive disease receive oral dexamethasone once daily on days 1-4 and oral thalidomide once daily on days 1-28. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

Patients are followed at 3 and 6 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 20-25 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: S0115, A Phase II Trial Evaluating Modified High Dose Melphalan (100 mg/m) And Autologous Peripheral Blood Stem Cell Supported Transplant (SCT) For High Risk Patients With Multiple Myeloma And/Or Light Chain Amyloidosis (AL Amyloidosis) (A BMT Study)
• Study Start Date: Jan 1, 2004
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment MM Induction: dexamethasone 20mg/d PO Days 1-4, 9-12 and 17-20 every 35 days for 2 cycles and thalidomide 200 mg/d PO Days 1-70. Mobilization and SC Collection: MM, MM+AL, MM+LCD: cyclophosphamide 2.5 gm/m2 IV Day 1; mesna 800 mg/m2 IV Day 1 x 3 doses; G-CSF 10 mcg/kg/d SQ Day 2 through day prior to last leukapheresis. Amyloid or LCDD-Only: G-CSF 16 mcg/kg/d SQ Days 1-3 (continued daily until the day prior to the last day of stem cell collection). Conditioning/Transplant - Modified HighDose Melphalan (given for both transplants): melphalan 100 mg/m2/d IV over 20 mins Day -2; PBSC infusion >/= 3.5 x 10^6 CD34+ cells/kg IV Day 0. Maintenance (MM only): dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year, followed by dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year.

Biological: filgrastim; Drug: cyclophosphamide; Drug: dexamethasone; Drug: melphalan; Drug: thalidomide; Procedure: peripheral blood stem cell transplantation

Outcome Measures

Primary Outcome Measures

1. Overall Survival [5 years from initial registration, or until death, whichever occurred earlier, on average, about 4.5 years]

   Time from initial registration until death or date of last contact, whichever occurs first, for up to 5 years from the date of the last patient registration.

Secondary Outcome Measures

1. Hematologic Response [Until off study]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• At least 1 of the following diagnoses:

• Multiple myeloma

• Stage II or III disease

• At least 1 of the following must be present:

• Serum M-protein of IgG, IgA, IgD, IgE greater than 1.0 g/dL

• Urinary M-protein (Bence-Jones) at least 200 mg/24 hours

• No IgM peaks except in patients who have physiologic criteria to support a diagnosis of multiple myeloma (e.g., bony lesions, myeloma kidney-cast nephropathy, absence of adenopathy [unless pathology-proven to be plasma cell infiltration])

• No monoclonal gammopathy of undetermined significance

• No indolent or smoldering myeloma

• No disease progression on prior thalidomide or dexamethasone

• Histologically confirmed primary systemic amyloidosis

• No senile, secondary, localized, dialysis-related, or familial amyloidosis

• No severe cardiac involvement

• No pre-exertional syncope, ventricular arrhythmia, or symptomatic pleural effusions associated with cardiac involvement

• Light Chain Deposition Disease alone or in combination with multiple myeloma meeting the following criteria:

• Deposition of granular material containing free light chains/immunoglobulins that did not bind Congo red

• Evidence of plasma cell dyscrasia (i.e., monoclonal gammopathy in the serum or urine by immunofixation electrophoresis and/or clonal plasmacytosis) on bone marrow biopsy by immunohistochemistry and/or elevated serum-free light chain concentration

• Must have been diagnosed within the past year

• Concurrent enrollment in the myeloma repository protocol SWOG-S0309 must be offered

PATIENT CHARACTERISTICS:

Age

• 18 and over (patients with amyloidosis only OR patients with amyloidosis and multiple myeloma OR patients with multiple myeloma only with poor renal function) OR

• 70 and over (patients with multiple myeloma only with or without poor renal function)

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,000/mm^3

• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 2.5 times upper limit of normal (ULN)

• SGOT or SGPT no greater than 2.5 times ULN

Renal

• No hemodialysis within 2 hours of melphalan or stem cell infusion

Cardiovascular

• See Disease Characteristics

• Hemodynamically stable (i.e., systolic blood pressure > 90 mm Hg in a lying position within the past 42 days)

• No myocardial infarction within the past 6 months

• No congestive heart failure

• No arrhythmia refractory to medical therapy

• LVEF greater than 45% by echocardiogram or MUGA

Pulmonary

• See Disease Characteristics

• No history of chronic obstructive or chronic restrictive pulmonary disease

• Pulmonary function studies (e.g., FEV_1 and FVC) at least 50% of predicted

• DLCO at least 50% of predicted

• Normal high resolution CT scan of the chest and acceptable arterial blood gases (i.e., PO_2 greater than 70) required for patients unable to complete pulmonary function tests due to bone pain or fracture

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Multiple myeloma patients receiving thalidomide must use 2 methods of effective contraception for at least 4 weeks before, during, and for at least 4 weeks after discontinuation of thalidomide

• HIV negative

• No other concurrent significant medical condition

• No concurrent uncontrolled life-threatening infection

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

• Prior cumulative melphalan dose no more than 200 mg

• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics

• No concurrent hormonal therapy

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy

• Prior or concurrent bisphosphonates allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
2	University of California Davis Cancer Center	Sacramento	California	United States	95817
3	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712
4	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
5	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas	United States	67401
6	Boston University Cancer Research Center	Boston	Massachusetts	United States	02118
7	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
8	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
9	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
10	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
11	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
12	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
13	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
14	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
15	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
16	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
17	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
18		Great Falls	Montana	United States	59405
19	Northern Montana Hospital	Havre	Montana	United States	59501
20	St. Peter's Hospital	Helena	Montana	United States	59601
21	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
22	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
23	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
24	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
25	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
26	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
27	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
28	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon	United States	97210
29	Northwest Cancer Specialists at Rose Quarter Cancer Center	Portland	Oregon	United States	97227
30	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
31	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
32	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
33	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195
34	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
35	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Vaishali Sanchorawala, MD, Boston Medical Center
• Study Chair: David C. Seldin, MD, PhD, Boston Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00064337
• Other Study ID Numbers: S0115; S0115; U10CA032102
• First Posted: Jul 9, 2003
• Last Update Posted: Aug 9, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Southwest Oncology Group: primary systemic amyloidosis; stage II multiple myeloma; stage III multiple myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Thalidomide; Dexamethasone; Cyclophosphamide; Melphalan

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/Group Description	MM Induction: dexamethasone 20mg/d PO Days 1-4, 9-12 and 17-20 every 35 days for 2 cycles and thalidomide 200 mg/d PO Days 1-70. Mobilization and SC Collection: MM, MM+AL, MM+LCD: cyclophosphamide 2.5 gm/m2 IV Day 1; mesna 800 mg/m2 IV Day 1 x 3 doses; G-CSF 10 mcg/kg/d SQ Day 2 through day prior to last leukapheresis. Amyloid or LCDD-Only: G-CSF 16 mcg/kg/d SQ Days 1-3 (continued daily until the day prior to the last day of stem cell collection). Conditioning/Transplant - Modified HighDose Melphalan (given for both transplants): melphalan 100 mg/m2/d IV over 20 mins Day -2; PBSC infusion >/= 3.5 x 10^6 CD34+ cells/kg IV Day 0. Maintenance (MM only): dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year, followed by dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year. filgrastim cyclophosphamide dexamethasone melphalan thalidomide peripheral blood
Period Title: PBSCC or Induction/PBSCC
STARTED	93
COMPLETED	73
NOT COMPLETED	20
Period Title: PBSCC or Induction/PBSCC
STARTED	67
COMPLETED	46
NOT COMPLETED	21
Period Title: PBSCC or Induction/PBSCC
STARTED	13
COMPLETED	3
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	MM Induction: dexamethasone 20mg/d PO Days 1-4, 9-12 and 17-20 every 35 days for 2 cycles and thalidomide 200 mg/d PO Days 1-70. Mobilization and SC Collection: MM, MM+AL, MM+LCD: cyclophosphamide 2.5 gm/m2 IV Day 1; mesna 800 mg/m2 IV Day 1 x 3 doses; G-CSF 10 mcg/kg/d SQ Day 2 through day prior to last leukapheresis. Amyloid or LCDD-Only: G-CSF 16 mcg/kg/d SQ Days 1-3 (continued daily until the day prior to the last day of stem cell collection). Conditioning/Transplant - Modified HighDose Melphalan (given for both transplants): melphalan 100 mg/m2/d IV over 20 mins Day -2; PBSC infusion >/= 3.5 x 10^6 CD34+ cells/kg IV Day 0. Maintenance (MM only): dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year, followed by dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year. filgrastim cyclophosphamide dexamethasone melphalan thalidomide peripheral blood
Overall Participants	93
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	35 37.6%
Male	58 62.4%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Time from initial registration until death or date of last contact, whichever occurs first, for up to 5 years from the date of the last patient registration.
Time Frame	5 years from initial registration, or until death, whichever occurred earlier, on average, about 4.5 years

Outcome Measure Data

Analysis Population Description

Eligible and analyzable patients only.

Arm/Group Title	Treatment
Arm/Group Description	MM Induction: dexamethasone 20mg/d PO Days 1-4, 9-12 and 17-20 every 35 days for 2 cycles and thalidomide 200 mg/d PO Days 1-70. Mobilization and SC Collection: MM, MM+AL, MM+LCD: cyclophosphamide 2.5 gm/m2 IV Day 1; mesna 800 mg/m2 IV Day 1 x 3 doses; G-CSF 10 mcg/kg/d SQ Day 2 through day prior to last leukapheresis. Amyloid or LCDD-Only: G-CSF 16 mcg/kg/d SQ Days 1-3 (continued daily until the day prior to the last day of stem cell collection). Conditioning/Transplant - Modified HighDose Melphalan (given for both transplants): melphalan 100 mg/m2/d IV over 20 mins Day -2; PBSC infusion >/= 3.5 x 10^6 CD34+ cells/kg IV Day 0. Maintenance (MM only): dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year, followed by dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year. filgrastim cyclophosphamide dexamethasone melphalan thalidomide peripheral blood
Measure Participants	93
Median (95% Confidence Interval) [Months]	68

2. Secondary Outcome

Title	Hematologic Response
Time Frame	Until off study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	MM Induction: dexamethasone 20mg/d PO Days 1-4, 9-12 and 17-20 every 35 days for 2 cycles and thalidomide 200 mg/d PO Days 1-70. Mobilization and SC Collection: MM, MM+AL, MM+LCD: cyclophosphamide 2.5 gm/m2 IV Day 1; mesna 800 mg/m2 IV Day 1 x 3 doses; G-CSF 10 mcg/kg/d SQ Day 2 through day prior to last leukapheresis. Amyloid or LCDD-Only: G-CSF 16 mcg/kg/d SQ Days 1-3 (continued daily until the day prior to the last day of stem cell collection). Conditioning/Transplant - Modified HighDose Melphalan (given for both transplants): melphalan 100 mg/m2/d IV over 20 mins Day -2; PBSC infusion >/= 3.5 x 10^6 CD34+ cells/kg IV Day 0. Maintenance (MM only): dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year, followed by dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year.
Measure Participants	23
Count of Participants [Participants]	8 8.6%

Adverse Events

Arm/Group Title	PBSCC or Induction/PBSCC		Autologous Transplants		Dex/Thal
Arm/Group Description	Induction/PBSCC - High Risk MM or MM with Light Chain Amyloidosis/Light Chain Disposition; PBSCC - Light Chain Amyloidosis/Light Chain Disposition		Autologous Transplants � All patients		Dex/Thal - High Risk MM or MM with Light Chain Amyloidosis/Light Chain Disposition
All Cause Mortality
	PBSCC or Induction/PBSCC		Autologous Transplants		Dex/Thal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	PBSCC or Induction/PBSCC		Autologous Transplants		Dex/Thal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/92 (4.3%)		3/65 (4.6%)		1/12 (8.3%)
Cardiac disorders
Cardiac General-Other	1/92 (1.1%)		0/65 (0%)		0/12 (0%)
Cardiac-ischemia/infarction	0/92 (0%)		1/65 (1.5%)		0/12 (0%)
Left ventricular diastolic dysfunction	1/92 (1.1%)		0/65 (0%)		0/12 (0%)
SVT and nodal arrhythmia - Nodal/junctional	0/92 (0%)		1/65 (1.5%)		0/12 (0%)
General disorders
Constitutional Symptoms-Other	1/92 (1.1%)		1/65 (1.5%)		0/12 (0%)
Investigations
Cardiac troponin I (cTnI)	0/92 (0%)		1/65 (1.5%)		0/12 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death - Disease progression NOS	0/92 (0%)		0/65 (0%)		1/12 (8.3%)
Renal and urinary disorders
Renal failure	1/92 (1.1%)		0/65 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	PBSCC or Induction/PBSCC		Autologous Transplants		Dex/Thal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	83/92 (90.2%)		62/65 (95.4%)		12/12 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	2/92 (2.2%)		20/65 (30.8%)		0/12 (0%)
Hemoglobin	43/92 (46.7%)		48/65 (73.8%)		6/12 (50%)
Lymphatics-Other	5/92 (5.4%)		8/65 (12.3%)		0/12 (0%)
Cardiac disorders
Cardiac Arrhythmia-Other	1/92 (1.1%)		12/65 (18.5%)		0/12 (0%)
Cardiac General-Other	5/92 (5.4%)		7/65 (10.8%)		0/12 (0%)
Ear and labyrinth disorders
Auditory/Ear-Other	1/92 (1.1%)		0/65 (0%)		1/12 (8.3%)
Endocrine disorders
Cushingoid appearance	2/92 (2.2%)		0/65 (0%)		1/12 (8.3%)
Eye disorders
Dry eye syndrome	0/92 (0%)		2/65 (3.1%)		1/12 (8.3%)
Ocular/Visual-Other	2/92 (2.2%)		2/65 (3.1%)		1/12 (8.3%)
Vision-blurred vision	2/92 (2.2%)		4/65 (6.2%)		2/12 (16.7%)
Gastrointestinal disorders
Constipation	20/92 (21.7%)		13/65 (20%)		3/12 (25%)
Diarrhea	13/92 (14.1%)		41/65 (63.1%)		1/12 (8.3%)
Distention/bloating, abdominal	0/92 (0%)		6/65 (9.2%)		0/12 (0%)
Dry mouth/salivary gland (xerostomia)	2/92 (2.2%)		11/65 (16.9%)		0/12 (0%)
Dysphagia (difficulty swallowing)	1/92 (1.1%)		4/65 (6.2%)		0/12 (0%)
Esophagitis	0/92 (0%)		4/65 (6.2%)		0/12 (0%)
Heartburn/dyspepsia	4/92 (4.3%)		6/65 (9.2%)		1/12 (8.3%)
Hemorrhage, GI - Lower GI NOS	0/92 (0%)		0/65 (0%)		1/12 (8.3%)
Hemorrhoids	0/92 (0%)		5/65 (7.7%)		0/12 (0%)
Mucositis/stomatitis (clinical exam) - Oral cavity	2/92 (2.2%)		13/65 (20%)		0/12 (0%)
Mucositis/stomatitis (functional/symp) - Oral cav	0/92 (0%)		4/65 (6.2%)		0/12 (0%)
Nausea	28/92 (30.4%)		44/65 (67.7%)		1/12 (8.3%)
Pain - Abdomen NOS	5/92 (5.4%)		9/65 (13.8%)		0/12 (0%)
Vomiting	18/92 (19.6%)		29/65 (44.6%)		0/12 (0%)
General disorders
Edema: limb	22/92 (23.9%)		19/65 (29.2%)		2/12 (16.7%)
Extremity-lower (gait/walking)	3/92 (3.3%)		1/65 (1.5%)		2/12 (16.7%)
Fatigue (asthenia, lethargy, malaise)	41/92 (44.6%)		41/65 (63.1%)		7/12 (58.3%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	5/92 (5.4%)		20/65 (30.8%)		0/12 (0%)
Pain-Other	2/92 (2.2%)		2/65 (3.1%)		1/12 (8.3%)
Rigors/chills	2/92 (2.2%)		7/65 (10.8%)		0/12 (0%)
Immune system disorders
Allergic reaction/hypersensitivity	0/92 (0%)		4/65 (6.2%)		1/12 (8.3%)
Infections and infestations
Inf (clin/microbio) w/Gr 3-4 neuts - Blood	1/92 (1.1%)		5/65 (7.7%)		0/12 (0%)
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	1/92 (1.1%)		0/65 (0%)		1/12 (8.3%)
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	0/92 (0%)		4/65 (6.2%)		0/12 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Catheter	1/92 (1.1%)		4/65 (6.2%)		0/12 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Up airway	3/92 (3.3%)		3/65 (4.6%)		3/12 (25%)
Inf w/unknown ANC - Middle ear (otitis media)	0/92 (0%)		0/65 (0%)		1/12 (8.3%)
Injury, poisoning and procedural complications
Bruising (in absence of Gr 3-4 thrombocytopenia)	2/92 (2.2%)		7/65 (10.8%)		0/12 (0%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	7/92 (7.6%)		14/65 (21.5%)		0/12 (0%)
AST, SGOT	6/92 (6.5%)		16/65 (24.6%)		1/12 (8.3%)
Alkaline phosphatase	23/92 (25%)		23/65 (35.4%)		0/12 (0%)
Bilirubin (hyperbilirubinemia)	4/92 (4.3%)		10/65 (15.4%)		1/12 (8.3%)
Cholesterol, serum-high (hypercholesterolemia)	0/92 (0%)		5/65 (7.7%)		0/12 (0%)
Creatinine	21/92 (22.8%)		30/65 (46.2%)		5/12 (41.7%)
GGT (gamma-glutamyl transpeptidase)	1/92 (1.1%)		10/65 (15.4%)		0/12 (0%)
INR (of prothrombin time)	2/92 (2.2%)		3/65 (4.6%)		1/12 (8.3%)
Leukocytes (total WBC)	18/92 (19.6%)		47/65 (72.3%)		5/12 (41.7%)
Lymphopenia	9/92 (9.8%)		11/65 (16.9%)		2/12 (16.7%)
Metabolic/Laboratory-Other	4/92 (4.3%)		5/65 (7.7%)		0/12 (0%)
Neutrophils/granulocytes (ANC/AGC)	10/92 (10.9%)		46/65 (70.8%)		3/12 (25%)
PTT (Partial thromboplastin time)	1/92 (1.1%)		5/65 (7.7%)		0/12 (0%)
Platelets	43/92 (46.7%)		49/65 (75.4%)		3/12 (25%)
Weight gain	6/92 (6.5%)		3/65 (4.6%)		2/12 (16.7%)
Weight loss	1/92 (1.1%)		13/65 (20%)		0/12 (0%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	24/92 (26.1%)		32/65 (49.2%)		1/12 (8.3%)
Anorexia	17/92 (18.5%)		24/65 (36.9%)		1/12 (8.3%)
Bicarbonate, serum-low	3/92 (3.3%)		5/65 (7.7%)		0/12 (0%)
Calcium, serum-low (hypocalcemia)	16/92 (17.4%)		31/65 (47.7%)		2/12 (16.7%)
Dehydration	4/92 (4.3%)		9/65 (13.8%)		0/12 (0%)
Glucose, serum-high (hyperglycemia)	33/92 (35.9%)		33/65 (50.8%)		6/12 (50%)
Magnesium, serum-high (hypermagnesemia)	2/92 (2.2%)		5/65 (7.7%)		0/12 (0%)
Magnesium, serum-low (hypomagnesemia)	8/92 (8.7%)		9/65 (13.8%)		0/12 (0%)
Phosphate, serum-low (hypophosphatemia)	5/92 (5.4%)		11/65 (16.9%)		1/12 (8.3%)
Potassium, serum-high (hyperkalemia)	4/92 (4.3%)		9/65 (13.8%)		2/12 (16.7%)
Potassium, serum-low (hypokalemia)	18/92 (19.6%)		15/65 (23.1%)		0/12 (0%)
Sodium, serum-low (hyponatremia)	10/92 (10.9%)		18/65 (27.7%)		1/12 (8.3%)
Triglyceride, serum-high (hypertriglyceridemia)	2/92 (2.2%)		4/65 (6.2%)		0/12 (0%)
Uric acid, serum-high (hyperuricemia)	9/92 (9.8%)		14/65 (21.5%)		0/12 (0%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - Extrem-lower	7/92 (7.6%)		4/65 (6.2%)		0/12 (0%)
Muscle weakness, not d/t neuropathy - Trunk	0/92 (0%)		0/65 (0%)		1/12 (8.3%)
Muscle weakness, not d/t neuropathy - body/general	7/92 (7.6%)		5/65 (7.7%)		1/12 (8.3%)
Pain - Back	6/92 (6.5%)		5/65 (7.7%)		2/12 (16.7%)
Pain - Bone	26/92 (28.3%)		9/65 (13.8%)		1/12 (8.3%)
Pain - Extremity-limb	1/92 (1.1%)		4/65 (6.2%)		0/12 (0%)
Pain - Joint	3/92 (3.3%)		6/65 (9.2%)		2/12 (16.7%)
Pain - Muscle	14/92 (15.2%)		12/65 (18.5%)		1/12 (8.3%)
Nervous system disorders
Dizziness	13/92 (14.1%)		17/65 (26.2%)		3/12 (25%)
Neuropathy: sensory	14/92 (15.2%)		8/65 (12.3%)		5/12 (41.7%)
Ocular/Visual-Other	2/92 (2.2%)		2/65 (3.1%)		1/12 (8.3%)
Pain - Head/headache	11/92 (12%)		14/65 (21.5%)		1/12 (8.3%)
Taste alteration (dysgeusia)	2/92 (2.2%)		15/65 (23.1%)		0/12 (0%)
Psychiatric disorders
Confusion	2/92 (2.2%)		5/65 (7.7%)		0/12 (0%)
Insomnia	9/92 (9.8%)		16/65 (24.6%)		0/12 (0%)
Mood alteration - depression	1/92 (1.1%)		4/65 (6.2%)		0/12 (0%)
Renal and urinary disorders
Hemorrhage, GU - Urinary NOS	3/92 (3.3%)		1/65 (1.5%)		1/12 (8.3%)
Proteinuria	1/92 (1.1%)		6/65 (9.2%)		0/12 (0%)
Renal failure	9/92 (9.8%)		9/65 (13.8%)		0/12 (0%)
Urinary frequency/urgency	3/92 (3.3%)		9/65 (13.8%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	5/92 (5.4%)		5/65 (7.7%)		0/12 (0%)
Cough	9/92 (9.8%)		15/65 (23.1%)		1/12 (8.3%)
Dyspnea (shortness of breath)	20/92 (21.7%)		17/65 (26.2%)		3/12 (25%)
Hemorrhage, pulmonary/upper respiratory - Nose	0/92 (0%)		5/65 (7.7%)		0/12 (0%)
Hiccoughs (hiccups, singultus)	0/92 (0%)		6/65 (9.2%)		0/12 (0%)
Hypoxia	3/92 (3.3%)		6/65 (9.2%)		0/12 (0%)
Pain - Throat/pharynx/larynx	4/92 (4.3%)		4/65 (6.2%)		0/12 (0%)
Pleural effusion (non-malignant)	5/92 (5.4%)		8/65 (12.3%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other	2/92 (2.2%)		2/65 (3.1%)		1/12 (8.3%)
Dry skin	1/92 (1.1%)		6/65 (9.2%)		0/12 (0%)
Hair loss/Alopecia (scalp or body)	3/92 (3.3%)		31/65 (47.7%)		0/12 (0%)
Petechiae/purpura (hemorrhage into skin or mucosa)	0/92 (0%)		4/65 (6.2%)		0/12 (0%)
Pruritus/itching	0/92 (0%)		6/65 (9.2%)		0/12 (0%)
Rash/desquamation	8/92 (8.7%)		19/65 (29.2%)		2/12 (16.7%)
Sweating (diaphoresis)	2/92 (2.2%)		3/65 (4.6%)		1/12 (8.3%)
Urticaria (hives, welts, wheals)	0/92 (0%)		4/65 (6.2%)		0/12 (0%)
Vascular disorders
Flushing	2/92 (2.2%)		4/65 (6.2%)		0/12 (0%)
Hematoma	0/92 (0%)		4/65 (6.2%)		0/12 (0%)
Hemorrhage/Bleeding-Other	10/92 (10.9%)		5/65 (7.7%)		0/12 (0%)
Hypertension	4/92 (4.3%)		7/65 (10.8%)		0/12 (0%)
Hypotension	15/92 (16.3%)		21/65 (32.3%)		0/12 (0%)
Thrombosis/thrombus/embolism	4/92 (4.3%)		0/65 (0%)		1/12 (8.3%)

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.