Lenalidomide in Treating Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00114101
• Collaborator: (none)
• Enrollment: 460
• Locations: 140
• Arms: 2
• Patients Per Site: 3.3

Study Details

Study Description

Brief Summary

This randomized phase III trial studies lenalidomide to see how well it works compared to a placebo in treating patients with multiple myeloma who are undergoing autologous stem cell transplant. Giving chemotherapy before a peripheral blood stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Biological therapies, such as lenalidomide, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Giving lenalidomide after autologous stem cell transplant may be an effective treatment for multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Smoldering Plasma Cell Myeloma	Procedure: Autologous Hematopoietic Stem Cell Transplantation; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Drug: Melphalan; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Placebo Administration	Phase 3

Detailed Description

PRIMARY OBJECTIVE:

1. To determine the efficacy of CC-5013 (lenalidomide) in prolonging time to disease progression in patients with multiple myeloma after autologous stem cell transplant (ASCT).

SECONDARY OBJECTIVES:

1. To determine if CC-5013 will increase the complete response (CR) rate in patients with multiple myeloma following ASCT.

2. To compare the progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma who have undergone ASCT and who then are randomized to either CC-5013 or placebo.

3. To determine the feasibility of long-term administration of CC-5013 to multiple myeloma patients who have undergone ASCT.

OUTLINE:

PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION: Mobilization of autologous PBSC will be performed according to institutional guidelines.

AUTOLOGOUS PBSC TRANSPLANTATION (PBSCT): Patients receive melphalan intravenously (IV) over 30-60 minutes on day -2 or -1 or over 2 days on days -3 and -2 or -2 and -1. Patients undergo autologous PBSCT on day 0.

Patients are then randomized to 1 of 2 maintenance treatment arms. (Note: As of 12/17/09, no more patients will be randomized between lenalidomide and placebo. Patients who have not been randomized as of 12/17/09 will be assigned to lenalidomide.)

ARM I: Beginning between day 100-110, patients receive lenalidomide orally (PO) once daily.

ARM II: Beginning between day 100-110, patients receive placebo (PO) once daily.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 460 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized, Double-Blind Study of Maintenance Therapy With CC-5013 (NSC # 703813) or Placebo Following Autologous Stem Cell Transplantation for Multiple Myeloma
• Actual Study Start Date: Dec 15, 2004
• Actual Primary Completion Date: Dec 31, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (melphalan, autologous PBSCT, lenalidomide) Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.	Procedure: Autologous Hematopoietic Stem Cell Transplantation; Undergo autologous PBSCT; Other Names: AHSCT Autologous Autologous Hematopoietic Cell Transplantation Autologous Stem Cell Transplant Autologous Stem Cell Transplantation Stem Cell Transplantation, Autologous ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid ; Drug: Melphalan; Given IV; Other Names: Alanine Nitrogen Mustard CB-3025 L-PAM L-Phenylalanine Mustard L-Sarcolysin L-Sarcolysin Phenylalanine mustard L-Sarcolysine Melphalanum Phenylalanine Mustard Phenylalanine Nitrogen Mustard Sarcoclorin Sarkolysin WR-19813 ; Procedure: Peripheral Blood Stem Cell Transplantation; Undergo autologous PBSCT; Other Names: PBPC transplantation PBSCT Peripheral Blood Peripheral Blood Progenitor Cell Transplantation PERIPHERAL BLOOD STEM CELL TRANSPLANT Peripheral Stem Cell Support Peripheral Stem Cell Transplant Peripheral Stem Cell Transplantation
Placebo Comparator: Arm II (melphalan, autologous PBSCT, placebo) Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.	Procedure: Autologous Hematopoietic Stem Cell Transplantation; Undergo autologous PBSCT; Other Names: AHSCT Autologous Autologous Hematopoietic Cell Transplantation Autologous Stem Cell Transplant Autologous Stem Cell Transplantation Stem Cell Transplantation, Autologous ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Melphalan; Given IV; Other Names: Alanine Nitrogen Mustard CB-3025 L-PAM L-Phenylalanine Mustard L-Sarcolysin L-Sarcolysin Phenylalanine mustard L-Sarcolysine Melphalanum Phenylalanine Mustard Phenylalanine Nitrogen Mustard Sarcoclorin Sarkolysin WR-19813 ; Procedure: Peripheral Blood Stem Cell Transplantation; Undergo autologous PBSCT; Other Names: PBPC transplantation PBSCT Peripheral Blood Peripheral Blood Progenitor Cell Transplantation PERIPHERAL BLOOD STEM CELL TRANSPLANT Peripheral Stem Cell Support Peripheral Stem Cell Transplant Peripheral Stem Cell Transplantation ; Other: Placebo Administration; Given PO

Outcome Measures

Primary Outcome Measures

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

   Time to progression (TTP) was defined as the date of transplant to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method. Progression was defined per the International Myeloma Working Group definition as one more of the following: 25% increase in serum M-component (absolute increase >= 0.5g/dl) 25% increase in urine M-component (absolute increase >= 200mg/24hour 25% increase in the difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl) 25 % increase in bone marrow plasma cell percentage (absolute increase of >=10%) Definite development of new bone lesion or soft tissue plasmacytomas Development of hypercalcemia

Secondary Outcome Measures

1. Response to Autologous Hematopoietic Stem-cell Transplant (HSCT) at Day 100 [Day 100]

   Response was defined according to International Myeloma Working Group criteria (2006) Complete Response: Complete disappearance of M-protein from serum & urine on immunofixation, normalization of Free Light Chain (FLC) ratio & <5% plasma cells in bone marrow (BM) Partial Response: >= 50% reduction in serum M-Component and/or Urine M-Component >= 90% reduction or <200 mg per 24 hours; or >= 50% decrease in difference between involved and uninvolved FLC levels Marginal Response: 25-49% reduction in serum M-component & urine M-component by 50-89% which still exceeds 200mg/24hour Progressive Disease: Defined in primary outcome measure Stable Disease: Not meeting any of the criteria above

Other Outcome Measures

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

   Overall Survival was measured from the date of randomization to date of death due to any cause. OS was estimated using the Kaplan Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have active multiple myeloma requiring treatment (Durie-Salmon stage >=

1. and have stable disease or be responsive to at least 2 months of any induction therapy; patients with smoldering myeloma are not eligible unless the disease has progressed to >= stage 1

• No more than 12 months of any prior therapy, including CC-5013 and thalidomide

• Within 12 months of initiation of induction therapy

• No prior progression after initial therapy; in addition, no more than two regimens will be allowed excluding dexamethasone alone

• No prior peripheral blood, bone marrow, or solid organ transplant

• Patients must have peripheral blood stem cell collection of >= 2 x 10^{6 cluster of differentiation (CD)34+ cells/kg (patient body weight) and preferably 5 x 10}6 cells/kg (patient body weight); stem cells may be collected at any time prior to transplant; peripheral blood stem cell collection may occur before or after registration

• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Patients must have diffusing capacity of the lung for carbon monoxide (DLCO) > 50% predicted with no symptomatic pulmonary disease

• Patients must have left ventricular ejection fraction (LVEF) >= 40% by multi gated acquisition scan (MUGA) or echocardiogram

• Patients must not have uncontrolled diabetes mellitus

• Patients must not have an active serious infection

• Patients must not be human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSag), or hepatitis (Hep) C positive

• Patients must be non-pregnant and non-nursing; women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL 10-14 days prior to registration and repeated within 24 hours prior to the first dose of lenalidomide; in addition, women of childbearing potential taking lenalidomide must have a pregnancy test performed by the doctor weekly during the first 4 weeks of treatment, and then every 4 weeks if menses are regular and every 2 weeks if menses are irregular, and then 30 days following the last dose of lenalidomide; women of childbearing potential must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control - one highly effective method (intrauterine device [IUD], hormonal, tubal ligation, or partner's vasectomy), and one additional effective method (latex condom, diaphragm, or cervical cap) - at the same time, at least 4 weeks before she begins lenalidomide therapy; "women of childbearing" potential is defined as a sexually mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months; men must agree not to father a child and must use a latex condom during any sexual contact with women of childbearing potential while taking lenalidomide and for 4 weeks after therapy is stopped, even if they have undergone a successful vasectomy

• Absolute neutrophil count (ANC) >= 1000/uL

• Platelets >= 100,000/uL

• Creatinine clearance* >= 40 cc/min

• To be calculated by method of Cockcroft-Gault or after 24-hour urine collection

• Creatinine =< 2 mg/dL

• Total bilirubin =< 2 mg/dL

• Aspartate aminotransferase (AST) =< 3 x upper limits of normal

• Alkaline phosphatase =< 3 x upper limits of normal

• Urine (U)-human chorionic gonadotropin (HCG) or serum HCG negative (if patient of childbearing potential)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
3	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
4	UC San Diego Medical Center - Hillcrest	San Diego	California	United States	92103
5	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
6	The Medical Center of Aurora	Aurora	Colorado	United States	80012
7	Boulder Community Hospital	Boulder	Colorado	United States	80301
8	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
9	Porter Adventist Hospital	Denver	Colorado	United States	80210
10	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
11	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
12	Rose Medical Center	Denver	Colorado	United States	80220
13	Western States Cancer Research NCORP	Denver	Colorado	United States	80222
14	Swedish Medical Center	Englewood	Colorado	United States	80113
15	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81501
16	North Colorado Medical Center	Greeley	Colorado	United States	80631
17	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
18	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
19	Longmont United Hospital	Longmont	Colorado	United States	80501
20	McKee Medical Center	Loveland	Colorado	United States	80539
21	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
22	North Suburban Medical Center	Thornton	Colorado	United States	80229
23	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
24	Beebe Medical Center	Lewes	Delaware	United States	19958
25	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
26	Saint Francis Hospital - Wilmington	Wilmington	Delaware	United States	19805
27	George Washington University Medical Center	Washington	District of Columbia	United States	20037
28	University of Florida Health Science Center - Gainesville	Gainesville	Florida	United States	32610
29	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
30	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
31	Northside Hospital	Atlanta	Georgia	United States	30342
32	Augusta University Medical Center	Augusta	Georgia	United States	30912
33	Saint Luke's Cancer Institute - Boise	Boise	Idaho	United States	83712
34	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
35	Graham Hospital Association	Canton	Illinois	United States	61520
36	Memorial Hospital	Carthage	Illinois	United States	62321
37	Jesse Brown Veterans Affairs Medical Center	Chicago	Illinois	United States	60612
38	University of Illinois	Chicago	Illinois	United States	60612
39	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
40	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
41	Eureka Hospital	Eureka	Illinois	United States	61530
42	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
43	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
44	Mason District Hospital	Havana	Illinois	United States	62644
45	Hopedale Medical Complex - Hospital	Hopedale	Illinois	United States	61747
46	Kewanee Hospital	Kewanee	Illinois	United States	61443
47	Mcdonough District Hospital	Macomb	Illinois	United States	61455
48	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
49	Carle Cancer Institute Normal	Normal	Illinois	United States	61761
50	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
51	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
52	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
53	Pekin Hospital	Pekin	Illinois	United States	61554
54	Proctor Hospital	Peoria	Illinois	United States	61614
55	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
56	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
57	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
58	Illinois Valley Hospital	Peru	Illinois	United States	61354
59	Perry Memorial Hospital	Princeton	Illinois	United States	61356
60	Saint Margaret's Hospital	Spring Valley	Illinois	United States	61362
61	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
62	Providence Medical Center	Kansas City	Kansas	United States	66112
63	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
64	Menorah Medical Center	Overland Park	Kansas	United States	66209
65	Radiation Oncology Practice Corporation Southwest	Overland Park	Kansas	United States	66210
66	Advent Health - Shawnee Mission Medical Center	Shawnee Mission	Kansas	United States	66204
67	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
68	Christiana Care - Union Hospital	Elkton	Maryland	United States	21921
69	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
70	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
71	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
72	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
73	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
74	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
75	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
76	Truman Medical Centers	Kansas City	Missouri	United States	64108
77	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
78	Radiation Oncology Practice Corporation South	Kansas City	Missouri	United States	64114
79	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
80	North Kansas City Hospital	Kansas City	Missouri	United States	64116
81	Research Medical Center	Kansas City	Missouri	United States	64132
82	Radiation Oncology Practice Corporation - North	Kansas City	Missouri	United States	64154
83	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
84	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
85	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
86	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
87	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
88	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
89	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
90	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
91	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
92	Montefiore Medical Center-Wakefield Campus	Bronx	New York	United States	10466
93	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
94	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
95	Northwell Health NCORP	Lake Success	New York	United States	11042
96	North Shore University Hospital	Manhasset	New York	United States	11030
97	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
98	Mount Sinai Hospital	New York	New York	United States	10029
99	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
100	NYP/Weill Cornell Medical Center	New York	New York	United States	10065
101	University of Rochester	Rochester	New York	United States	14642
102	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
103	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
104	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
105	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
106	The Jewish Hospital	Cincinnati	Ohio	United States	45236
107	Case Western Reserve University	Cleveland	Ohio	United States	44106
108	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
109	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
110	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
111	Providence Portland Medical Center	Portland	Oregon	United States	97213
112	Oregon Health and Science University	Portland	Oregon	United States	97239
113	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
114	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
115	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
116	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
117	West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224
118	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
119	Geisinger Medical Group	State College	Pennsylvania	United States	16801
120	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
121	Saint Francis Hospital	Greenville	South Carolina	United States	29601
122	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
123	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
124	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
125	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
126	Houston Methodist Hospital	Houston	Texas	United States	77030
127	M D Anderson Cancer Center	Houston	Texas	United States	77030
128	LDS Hospital	Salt Lake City	Utah	United States	84143
129	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
130	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
131	Virginia Oncology Associates-Hampton	Hampton	Virginia	United States	23666
132	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
133	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
134	Saint Mary's Medical Center	Huntington	West Virginia	United States	25702
135	Aurora Cancer Care-Glendale	Glendale	Wisconsin	United States	53212
136	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
137	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
138	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
139	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
140	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin	United States	54868

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Philip L McCarthy, Alliance for Clinical Trials in Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00114101
• Other Study ID Numbers: NCI-2009-00439; NCI-2009-00439; CALGB 100104/ECOG 100104; CDR0000434845; CALGB-100104; CALGB-100104; U10CA180821; U10CA031946
• First Posted: Jun 14, 2005
• Last Update Posted: Jul 28, 2022
• Last Verified: May 1, 2022

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Lenalidomide; Melphalan; Mechlorethamine; Nitrogen Mustard Compounds

Study Results

Participant Flow

Recruitment Details	From December 2004 and July 2009, a total of 568 participants were recruited to this study.
Pre-assignment Detail	After registration, participants underwent a peripheral blood stem cell transplant. Of the 568 participants, 460 were randomized to either arm, stratified by beta2 microglobulin, prior thalidomide use and prior lenalidomide use. (108 participants dropped out prior to randomization, most common reasons include: progression, ineligible, refusal)

Arm/Group Title	Lenalidomide Maintenance	Placebo Maintenance
Arm/Group Description	Beginning between day 100-110, patients receive oral lenalidomide once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day.	Beginning between day 100-110, patients receive oral placebo once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day. (closed as of 12/17/09)
Period Title: Overall Study
STARTED	231	229
COMPLETED	231	229
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Lenalidomide Maintenance	Placebo Maintenance	Total
Arm/Group Description	Beginning between day 100-110, patients receive oral lenalidomide once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day.	Beginning between day 100-110, patients receive oral placebo once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day. (closed as of 12/17/09)	Total of all reporting groups
Overall Participants	231	229	460
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59	58	59
Sex: Female, Male (Count of Participants)
Female	110 47.6%	100 43.7%	210 45.7%
Male	121 52.4%	129 56.3%	250 54.3%
Region of Enrollment (participants) [Number]
United States	231 100%	229 100%	460 100%
Beta 2 microglobulin at registration (participants) [Number]
> 2.5 mg/liter	50 21.6%	55 24%	105 22.8%
<= 2.5 mg/liter	170 73.6%	163 71.2%	333 72.4%
Missing data	11 4.8%	11 4.8%	22 4.8%
Prior use of thalidomide during induction (participants) [Number]
Yes	102 44.2%	103 45%	205 44.6%
No	129 55.8%	126 55%	255 55.4%
Prior use of lenalidomide during induction therapy (participants) [Number]
Yes	79 34.2%	81 35.4%	160 34.8%
No	152 65.8%	148 64.6%	300 65.2%

Outcome Measures

1. Primary Outcome

Title	Time to Progression
Description	Time to progression (TTP) was defined as the date of transplant to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method. Progression was defined per the International Myeloma Working Group definition as one more of the following: 25% increase in serum M-component (absolute increase >= 0.5g/dl) 25% increase in urine M-component (absolute increase >= 200mg/24hour 25% increase in the difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl) 25 % increase in bone marrow plasma cell percentage (absolute increase of >=10%) Definite development of new bone lesion or soft tissue plasmacytomas Development of hypercalcemia
Time Frame	Duration of study (up to 10years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide Maintenance	Placebo Maintenance
Arm/Group Description	Beginning between day 100-110, patients receive oral lenalidomide once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day.	Beginning between day 100-110, patients receive oral placebo once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day. (closed as of 12/17/09)
Measure Participants	231	229
Median (95% Confidence Interval) [months]	39	21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide Maintenance, Placebo Maintenance
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	This study was designed to have 80% power, with the use of the log-rank test at a one-sided significance level of 0.05, to detect a hazard ratio of 1.4, assuming proportional hazards and an exponential time to event distribution. Under the assumed framework, 309 events were expected. The expected drop out rate before randomization was 15%.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Participants were randomized with the use of a permuted-block design stratified by beta 2 microglobulin, prior use of thalidomide and prior use of lenalidomide. TTP was monitored with the use of a group sequential design for superiority and futility.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.36
	Confidence Interval	(2-Sided) 95%; 0.26 to 0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Response to Autologous Hematopoietic Stem-cell Transplant (HSCT) at Day 100
Description	Response was defined according to International Myeloma Working Group criteria (2006) Complete Response: Complete disappearance of M-protein from serum & urine on immunofixation, normalization of Free Light Chain (FLC) ratio & <5% plasma cells in bone marrow (BM) Partial Response: >= 50% reduction in serum M-Component and/or Urine M-Component >= 90% reduction or <200 mg per 24 hours; or >= 50% decrease in difference between involved and uninvolved FLC levels Marginal Response: 25-49% reduction in serum M-component & urine M-component by 50-89% which still exceeds 200mg/24hour Progressive Disease: Defined in primary outcome measure Stable Disease: Not meeting any of the criteria above
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide Maintenance	Placebo Maintenance
Arm/Group Description	Beginning between day 100-110, patients receive oral lenalidomide once daily.	Beginning between day 100-110, patients receive oral placebo once daily. (closed as of 12/17/09)
Measure Participants	231	229
Complete response	67 29%	79 34.5%
Partial response	115 49.8%	109 47.6%
Marginal response	11 4.8%	5 2.2%
Stable disease	38 16.5%	32 14%
Progressive disease	0 0%	3 1.3%
Unknown	0 0%	1 0.4%

3. Other Pre-specified Outcome

Title	Overall Survival
Description	Overall Survival was measured from the date of randomization to date of death due to any cause. OS 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	Lenalidomide Maintenance	Placebo Maintenance
Arm/Group Description	Beginning between day 100-110, patients receive oral lenalidomide once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day.	Beginning between day 100-110, patients receive oral placebo once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day. (closed as of 12/17/09)
Measure Participants	231	229
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide Maintenance, Placebo Maintenance
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.26 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Post-Hoc Outcome

Title	Number of Participants With Progression, Death or Diagnosis of Second Primary Malignancy
Description	Patients who develop progression (defined in primary outcome measure), died or develop a new primary malignancy (cancer) will summarized in this outcome.
Time Frame	Duration of study (up to 10 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide Maintenance	Placebo Maintenance
Arm/Group Description	Beginning between day 100-110, patients receive oral lenalidomide once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day.	Beginning between day 100-110, patients receive oral placebo once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day. (closed as of 12/17/09)
Measure Participants	231	229
Number [participants]	92 39.8%	133 58.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide Maintenance, Placebo Maintenance
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; 0.41 to 0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Lenalidomide Maintenance		Placebo Maintenance
Arm/Group Description	Beginning between day 100-110, patients receive oral lenalidomide once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day.		Beginning between day 100-110, patients receive oral placebo once daily - 10 mg/day for the first 3 months, then if tolerated, 15 mg/day. (closed as of 12/17/09)
All Cause Mortality
	Lenalidomide Maintenance		Placebo Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lenalidomide Maintenance		Placebo Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/231 (22.5%)		33/229 (14.4%)
Blood and lymphatic system disorders
Febrile neutropenia	6/231 (2.6%)	6	2/229 (0.9%)	2
Hemoglobin	8/231 (3.5%)	8	5/229 (2.2%)	5
Hemolysis (e.g. immune hemolytic anemia drug-related hemolysis)	1/231 (0.4%)	1	0/229 (0%)	0
Cardiac disorders
Cardiac Arrhythmia - Other	0/231 (0%)	0	1/229 (0.4%)	1
Cardiac ischemia/infarction	0/231 (0%)	0	1/229 (0.4%)	1
Conduction abnormality/atrioventricular heart block	1/231 (0.4%)	1	2/229 (0.9%)	2
Left ventricular systolic dysfunction	0/231 (0%)	0	1/229 (0.4%)	1
Restrictive cardiomyopathy	1/231 (0.4%)	1	0/229 (0%)	0
Supraventricular and nodal arrhythmia	1/231 (0.4%)	1	2/229 (0.9%)	2
Endocrine disorders
Thyroid function high (hyperthyroidism thyrotoxicosis)	1/231 (0.4%)	1	0/229 (0%)	0
Thyroid function, low (hypothyroidism)	0/231 (0%)	0	1/229 (0.4%)	1
Eye disorders
Cataract	1/231 (0.4%)	1	0/229 (0%)	0
Ocular/Visual - Other	1/231 (0.4%)	1	0/229 (0%)	0
Gastrointestinal disorders
Constipation	1/231 (0.4%)	1	0/229 (0%)	0
Diarrhea	19/231 (8.2%)	22	9/229 (3.9%)	9
Distension/bloating, abdominal	0/231 (0%)	0	1/229 (0.4%)	1
Esophagitis	1/231 (0.4%)	1	1/229 (0.4%)	1
Gastrointestinal - Other	1/231 (0.4%)	1	2/229 (0.9%)	2
Heartburn/dyspepsia	0/231 (0%)	0	1/229 (0.4%)	1
Hemorrhage, GI	0/231 (0%)	0	1/229 (0.4%)	1
Nausea	5/231 (2.2%)	5	4/229 (1.7%)	4
Obstruction GI	0/231 (0%)	0	1/229 (0.4%)	1
Pancreatitis	0/231 (0%)	0	2/229 (0.9%)	2
Ulcer, GI	0/231 (0%)	0	2/229 (0.9%)	2
Vomiting	1/231 (0.4%)	1	3/229 (1.3%)	3
General disorders
Constitutional Symptoms - Other	0/231 (0%)	0	2/229 (0.9%)	2
Death not associated with CTCAE term	2/231 (0.9%)	2	2/229 (0.9%)	2
Edema: limb	1/231 (0.4%)	1	2/229 (0.9%)	2
Fatigue (asthenia, lethargy, malaise)	3/231 (1.3%)	3	2/229 (0.9%)	2
Fever	3/231 (1.3%)	3	4/229 (1.7%)	4
Pain - Other	1/231 (0.4%)	1	2/229 (0.9%)	2
Rigors/chills	1/231 (0.4%)	1	0/229 (0%)	0
Hepatobiliary disorders
Liver dysfunction/failure (clinical)	0/231 (0%)	0	1/229 (0.4%)	1
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)	0/231 (0%)	0	1/229 (0.4%)	1
Infection	16/231 (6.9%)	18	7/229 (3.1%)	7
Infection - Other	4/231 (1.7%)	4	1/229 (0.4%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils	14/231 (6.1%)	14	9/229 (3.9%)	13
Infection with unknown ANC	0/231 (0%)	0	7/229 (3.1%)	8
Infection without neutropenia	1/231 (0.4%)	1	0/229 (0%)	0
Injury, poisoning and procedural complications
Fracture	1/231 (0.4%)	1	1/229 (0.4%)	1
Thrombosis/embolism (vascular access-related)	0/231 (0%)	0	1/229 (0.4%)	1
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	3/231 (1.3%)	3	1/229 (0.4%)	1
AST, SGOT(serum glutamic oxaloacetic transaminase)	4/231 (1.7%)	4	1/229 (0.4%)	1
Alkaline phosphatase	0/231 (0%)	0	1/229 (0.4%)	1
Bilirubin (hyperbilirubinemia)	10/231 (4.3%)	12	4/229 (1.7%)	5
Cardiac troponin I (cTnI)	0/231 (0%)	0	1/229 (0.4%)	1
Creatinine	1/231 (0.4%)	2	3/229 (1.3%)	3
Fibrinogen	0/231 (0%)	0	1/229 (0.4%)	1
INR (International Normalized Ratio of prothrombin time)	2/231 (0.9%)	2	1/229 (0.4%)	1
Leukocytes (total WBC)	10/231 (4.3%)	11	2/229 (0.9%)	2
Lipase	0/231 (0%)	0	1/229 (0.4%)	1
Lymphopenia	5/231 (2.2%)	5	3/229 (1.3%)	3
Metabolic/Laboratory - Other	1/231 (0.4%)	1	1/229 (0.4%)	1
Neutrophils/granulocytes (ANC/AGC)	40/231 (17.3%)	47	14/229 (6.1%)	16
PTT (Partial Thromboplastin Time)	0/231 (0%)	0	1/229 (0.4%)	1
Platelets	39/231 (16.9%)	45	16/229 (7%)	21
Weight gain	1/231 (0.4%)	1	3/229 (1.3%)	3
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)	0/231 (0%)	0	1/229 (0.4%)	1
Albumin, serum-low (hypoalbuminemia)	2/231 (0.9%)	2	3/229 (1.3%)	3
Anorexia	2/231 (0.9%)	2	1/229 (0.4%)	1
Calcium serum-high (hypercalcemia)	0/231 (0%)	0	1/229 (0.4%)	1
Calcium serum-low (hypocalcemia)	1/231 (0.4%)	1	1/229 (0.4%)	1
Dehydration	1/231 (0.4%)	1	4/229 (1.7%)	4
Glucose serum-high (hyperglycemia)	0/231 (0%)	0	1/229 (0.4%)	1
Glucose serum-low (hypoglycemia)	0/231 (0%)	0	1/229 (0.4%)	1
Magnesium serum-low (hypomagnesemia)	1/231 (0.4%)	1	2/229 (0.9%)	2
Phosphate serum-low (hypophosphatemia)	3/231 (1.3%)	4	3/229 (1.3%)	3
Potassium serum-high (hyperkalemia)	0/231 (0%)	0	2/229 (0.9%)	2
Potassium serum-low (hypokalemia)	3/231 (1.3%)	3	3/229 (1.3%)	3
Sodium serum-low (hyponatremia)	0/231 (0%)	0	1/229 (0.4%)	1
Musculoskeletal and connective tissue disorders
Osteonecrosis (avascular necrosis)	1/231 (0.4%)	1	0/229 (0%)	0
Pain	6/231 (2.6%)	8	9/229 (3.9%)	12
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy - possibly related to cancer treatment	1/231 (0.4%)	1	0/229 (0%)	0
Nervous system disorders
CNS cerebrovascular ischemia	1/231 (0.4%)	1	2/229 (0.9%)	2
Dizziness	1/231 (0.4%)	1	0/229 (0%)	0
Memory impairment	1/231 (0.4%)	1	0/229 (0%)	0
Mental status	1/231 (0.4%)	1	0/229 (0%)	0
Neurology - Other	0/231 (0%)	0	1/229 (0.4%)	1
Neuropathy: motor	1/231 (0.4%)	1	0/229 (0%)	0
Neuropathy: sensory	1/231 (0.4%)	1	2/229 (0.9%)	2
Seizure	0/231 (0%)	0	1/229 (0.4%)	1
Somnolence/depressed level of consciousness	0/231 (0%)	0	1/229 (0.4%)	1
Syncope (fainting)	2/231 (0.9%)	2	2/229 (0.9%)	2
Psychiatric disorders
Confusion	0/231 (0%)	0	2/229 (0.9%)	2
Mood alteration	4/231 (1.7%)	4	1/229 (0.4%)	1
Renal and urinary disorders
Renal failure	1/231 (0.4%)	2	2/229 (0.9%)	3
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)	0/231 (0%)	0	1/229 (0.4%)	1
Cough	3/231 (1.3%)	3	2/229 (0.9%)	2
Dyspnea (shortness of breath)	3/231 (1.3%)	3	5/229 (2.2%)	5
Hypoxia	3/231 (1.3%)	3	3/229 (1.3%)	4
Pneumonitis/pulmonary infiltrates	3/231 (1.3%)	4	4/229 (1.7%)	5
Pulmonary/Upper Respiratory - Other	1/231 (0.4%)	1	1/229 (0.4%)	1
Skin and subcutaneous tissue disorders
Pruritus/itching	1/231 (0.4%)	1	0/229 (0%)	0
Rash/desquamation	6/231 (2.6%)	6	4/229 (1.7%)	5
Rash: hand-foot skin reaction	0/231 (0%)	0	1/229 (0.4%)	1
Vascular disorders
Hypertension	0/231 (0%)	0	3/229 (1.3%)	3
Hypotension	1/231 (0.4%)	1	2/229 (0.9%)	2
Thrombosis/thrombus/embolism	2/231 (0.9%)	2	1/229 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Lenalidomide Maintenance		Placebo Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	195/231 (84.4%)		166/229 (72.5%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Other	2/231 (0.9%)	4	1/229 (0.4%)	1
Febrile neutropenia	9/231 (3.9%)	10	3/229 (1.3%)	4
Hemoglobin	26/231 (11.3%)	45	9/229 (3.9%)	22
Hemolysis (e.g. immune hemolytic anemia drug-related hemolysis)	0/231 (0%)	0	2/229 (0.9%)	2
Cardiac disorders
Cardiac General - Other	1/231 (0.4%)	1	1/229 (0.4%)	1
Conduction abnormality/atrioventricular heart block	1/231 (0.4%)	1	0/229 (0%)	0
Edema	1/231 (0.4%)	1	0/229 (0%)	0
Left ventricular systolic dysfunction	0/231 (0%)	0	1/229 (0.4%)	1
Palpitations	2/231 (0.9%)	2	1/229 (0.4%)	1
Supraventricular and nodal arrhythmia	3/231 (1.3%)	3	1/229 (0.4%)	1
Ventricular arrhythmia	0/231 (0%)	0	1/229 (0.4%)	2
Ear and labyrinth disorders
Hearing: patients without baseline audiogram and not enrolled in a monitoring program	0/231 (0%)	0	1/229 (0.4%)	1
Tinnitus	1/231 (0.4%)	1	0/229 (0%)	0
Endocrine disorders
Thyroid function high (hyperthyroidism thyrotoxicosis)	0/231 (0%)	0	1/229 (0.4%)	1
Thyroid function, low (hypothyroidism)	1/231 (0.4%)	2	2/229 (0.9%)	2
Eye disorders
Cataract	1/231 (0.4%)	1	1/229 (0.4%)	1
Ocular/Visual - Other	0/231 (0%)	0	4/229 (1.7%)	4
Vision-blurred vision	1/231 (0.4%)	1	1/229 (0.4%)	2
Watery eye (epiphora tearing)	0/231 (0%)	0	2/229 (0.9%)	3
Gastrointestinal disorders
Colitis	1/231 (0.4%)	1	1/229 (0.4%)	1
Constipation	9/231 (3.9%)	10	7/229 (3.1%)	12
Dental: periodontal disease	0/231 (0%)	0	1/229 (0.4%)	1
Diarrhea	89/231 (38.5%)	227	52/229 (22.7%)	90
Distension/bloating, abdominal	0/231 (0%)	0	2/229 (0.9%)	2
Dry mouth/salivary gland (xerostomia)	1/231 (0.4%)	2	3/229 (1.3%)	4
Dysphagia (difficulty swallowing)	1/231 (0.4%)	1	1/229 (0.4%)	1
Esophagitis	1/231 (0.4%)	1	0/229 (0%)	0
Gastritis (including bile reflux gastritis)	0/231 (0%)	0	2/229 (0.9%)	2
Gastrointestinal - Other	3/231 (1.3%)	3	1/229 (0.4%)	1
Heartburn/dyspepsia	3/231 (1.3%)	3	0/229 (0%)	0
Hemorrhage, GI	1/231 (0.4%)	1	0/229 (0%)	0
Hemorrhoids	0/231 (0%)	0	1/229 (0.4%)	1
Melena/GI bleeding	0/231 (0%)	0	1/229 (0.4%)	1
Mucositis/stomatitis (clinical exam)	2/231 (0.9%)	2	1/229 (0.4%)	1
Mucositis/stomatitis (functional/symptomatic)	1/231 (0.4%)	1	1/229 (0.4%)	1
Nausea	13/231 (5.6%)	15	10/229 (4.4%)	15
Stomatitis/pharyngitis (oral/pharyngeal mucositis) for BMT studies if specified in the protocol.	1/231 (0.4%)	1	0/229 (0%)	0
Vomiting	9/231 (3.9%)	10	6/229 (2.6%)	9
General disorders
Constitutional Symptoms - Other	0/231 (0%)	0	2/229 (0.9%)	2
Edema: limb	4/231 (1.7%)	5	3/229 (1.3%)	3
Edema:head and neck	1/231 (0.4%)	1	0/229 (0%)	0
Fatigue (asthenia, lethargy, malaise)	36/231 (15.6%)	55	29/229 (12.7%)	54
Fever	9/231 (3.9%)	10	2/229 (0.9%)	2
Flu-like syndrome	1/231 (0.4%)	1	0/229 (0%)	0
Pain - Other	1/231 (0.4%)	1	8/229 (3.5%)	14
Rigors/chills	4/231 (1.7%)	6	1/229 (0.4%)	3
Syndromes - Other	0/231 (0%)	0	1/229 (0.4%)	1
Hepatobiliary disorders
Cholecystitis	2/231 (0.9%)	2	0/229 (0%)	0
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	0/231 (0%)	0	1/229 (0.4%)	1
Allergy/Immunology - Other	2/231 (0.9%)	2	0/229 (0%)	0
Infections and infestations
Infection	16/231 (6.9%)	17	11/229 (4.8%)	14
Infection - Other	6/231 (2.6%)	6	3/229 (1.3%)	3
Infection with normal ANC or Grade 1 or 2 neutrophils	11/231 (4.8%)	14	14/229 (6.1%)	18
Infection with unknown ANC	15/231 (6.5%)	18	9/229 (3.9%)	11
Infection without neutropenia	2/231 (0.9%)	3	1/229 (0.4%)	1
Opportunistic infection associated with >=Grade 2 Lymphopenia	1/231 (0.4%)	1	1/229 (0.4%)	1
Viral hepatitis	1/231 (0.4%)	1	0/229 (0%)	0
Injury, poisoning and procedural complications
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	0/231 (0%)	0	1/229 (0.4%)	1
Burn	1/231 (0.4%)	1	0/229 (0%)	0
Fracture	1/231 (0.4%)	1	2/229 (0.9%)	2
Intra-operative injury	0/231 (0%)	0	1/229 (0.4%)	1
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	11/231 (4.8%)	13	2/229 (0.9%)	3
AST, SGOT(serum glutamic oxaloacetic transaminase)	7/231 (3%)	8	3/229 (1.3%)	5
Alkaline phosphatase	5/231 (2.2%)	5	4/229 (1.7%)	4
Bilirubin (hyperbilirubinemia)	24/231 (10.4%)	66	18/229 (7.9%)	36
CPK (creatine phosphokinase)	1/231 (0.4%)	3	0/229 (0%)	0
Creatinine	2/231 (0.9%)	2	5/229 (2.2%)	9
GGT (gamma-Glutamyl transpeptidase)	0/231 (0%)	0	1/229 (0.4%)	1
INR (International Normalized Ratio of prothrombin time)	3/231 (1.3%)	7	0/229 (0%)	0
Leukocytes (total WBC)	29/231 (12.6%)	72	14/229 (6.1%)	33
Lymphopenia	17/231 (7.4%)	31	9/229 (3.9%)	23
Metabolic/Laboratory - Other	2/231 (0.9%)	3	3/229 (1.3%)	4
Neutrophils/granulocytes (ANC/AGC)	153/231 (66.2%)	593	75/229 (32.8%)	181
PTT (Partial Thromboplastin Time)	0/231 (0%)	0	2/229 (0.9%)	2
Platelets	129/231 (55.8%)	445	78/229 (34.1%)	200
Weight gain	13/231 (5.6%)	21	21/229 (9.2%)	33
Weight loss	1/231 (0.4%)	2	1/229 (0.4%)	1
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	1/231 (0.4%)	1	2/229 (0.9%)	2
Anorexia	5/231 (2.2%)	5	6/229 (2.6%)	7
Calcium serum-high (hypercalcemia)	0/231 (0%)	0	2/229 (0.9%)	3
Calcium serum-low (hypocalcemia)	6/231 (2.6%)	6	5/229 (2.2%)	6
Dehydration	0/231 (0%)	0	1/229 (0.4%)	1
Glucose serum-high (hyperglycemia)	8/231 (3.5%)	12	7/229 (3.1%)	18
Glucose serum-low (hypoglycemia)	3/231 (1.3%)	3	1/229 (0.4%)	2
Phosphate serum-low (hypophosphatemia)	2/231 (0.9%)	2	3/229 (1.3%)	4
Potassium serum-high (hyperkalemia)	3/231 (1.3%)	3	1/229 (0.4%)	1
Potassium serum-low (hypokalemia)	9/231 (3.9%)	11	4/229 (1.7%)	7
Sodium serum-low (hyponatremia)	2/231 (0.9%)	2	1/229 (0.4%)	1
Triglyceride serum-high (hypertriglyceridemia)	1/231 (0.4%)	1	0/229 (0%)	0
Uric acid serum-high (hyperuricemia)	0/231 (0%)	0	2/229 (0.9%)	2
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/231 (0.4%)	1	1/229 (0.4%)	1
Joint-function	1/231 (0.4%)	1	0/229 (0%)	0
Lumbar spine-range of motion	0/231 (0%)	0	1/229 (0.4%)	2
Muscle weakness, generalized or specific area (not due to neuropathy)	1/231 (0.4%)	1	2/229 (0.9%)	3
Musculoskeletal/Soft Tissue - Other	0/231 (0%)	0	4/229 (1.7%)	4
Myositis (inflammation/damage of muscle)	0/231 (0%)	0	2/229 (0.9%)	2
Pain	35/231 (15.2%)	84	50/229 (21.8%)	154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy - possibly related to cancer treatment	5/231 (2.2%)	5	1/229 (0.4%)	1
Nervous system disorders
Ataxia (incoordination)	2/231 (0.9%)	3	0/229 (0%)	0
Dizziness	4/231 (1.7%)	8	8/229 (3.5%)	9
Headache	0/231 (0%)	0	1/229 (0.4%)	1
Hemorrhage CNS	1/231 (0.4%)	1	0/229 (0%)	0
Memory impairment	1/231 (0.4%)	1	1/229 (0.4%)	1
Neurology - Other	1/231 (0.4%)	1	4/229 (1.7%)	4
Neuropathy: cranial	0/231 (0%)	0	1/229 (0.4%)	1
Neuropathy: motor	6/231 (2.6%)	10	4/229 (1.7%)	6
Neuropathy: sensory	24/231 (10.4%)	40	24/229 (10.5%)	49
Somnolence/depressed level of consciousness	1/231 (0.4%)	1	0/229 (0%)	0
Speech impairment (e.g., dysphasia or aphasia)	0/231 (0%)	0	1/229 (0.4%)	1
Syncope (fainting)	1/231 (0.4%)	1	0/229 (0%)	0
Taste alteration (dysgeusia)	1/231 (0.4%)	1	0/229 (0%)	0
Tremor	1/231 (0.4%)	1	0/229 (0%)	0
Psychiatric disorders
Insomnia	6/231 (2.6%)	6	7/229 (3.1%)	15
Libido	1/231 (0.4%)	1	1/229 (0.4%)	1
Mood alteration	9/231 (3.9%)	12	11/229 (4.8%)	16
Renal and urinary disorders
Hemorrhage GU	1/231 (0.4%)	1	2/229 (0.9%)	2
Renal failure	3/231 (1.3%)	3	3/229 (1.3%)	3
Renal/Genitourinary - Other	1/231 (0.4%)	1	3/229 (1.3%)	3
Urinary frequency/urgency	2/231 (0.9%)	3	4/229 (1.7%)	4
Urinary retention (including neurogenic bladder)	1/231 (0.4%)	1	0/229 (0%)	0
Reproductive system and breast disorders
Vaginal discharge (non-infectious)	0/231 (0%)	0	1/229 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)	0/231 (0%)	0	1/229 (0.4%)	1
Allergic rhinitis (including sneezing nasal stuffiness postnasal drip)	2/231 (0.9%)	2	4/229 (1.7%)	7
Apnea	0/231 (0%)	0	1/229 (0.4%)	1
Bronchospasm wheezing	0/231 (0%)	0	1/229 (0.4%)	1
Cough	10/231 (4.3%)	12	9/229 (3.9%)	13
Dyspnea (shortness of breath)	4/231 (1.7%)	5	4/229 (1.7%)	8
Hemorrhage pulmonary/upper respiratory	1/231 (0.4%)	1	1/229 (0.4%)	1
Hypoxia	0/231 (0%)	0	2/229 (0.9%)	2
Pleural effusion (non-malignant)	1/231 (0.4%)	1	1/229 (0.4%)	1
Pneumonitis/pulmonary infiltrates	8/231 (3.5%)	8	11/229 (4.8%)	12
Pulmonary/Upper Respiratory - Other	3/231 (1.3%)	3	5/229 (2.2%)	5
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other	2/231 (0.9%)	2	0/229 (0%)	0
Dry skin	6/231 (2.6%)	8	4/229 (1.7%)	5
Hair loss/alopecia (scalp or body)	1/231 (0.4%)	1	0/229 (0%)	0
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	0/231 (0%)	0	1/229 (0.4%)	2
Pruritus/itching	5/231 (2.2%)	5	3/229 (1.3%)	4
Rash/desquamation	57/231 (24.7%)	86	36/229 (15.7%)	56
Sweating (diaphoresis)	4/231 (1.7%)	6	4/229 (1.7%)	5
Ulceration	1/231 (0.4%)	1	0/229 (0%)	0
Urticaria (hives welts wheals)	0/231 (0%)	0	2/229 (0.9%)	2
Vascular disorders
Hematoma	2/231 (0.9%)	2	0/229 (0%)	0
Hemorrhage/Bleeding - Other	0/231 (0%)	0	1/229 (0.4%)	1
Hot flashes/flushes	3/231 (1.3%)	4	0/229 (0%)	0
Hypertension	2/231 (0.9%)	2	2/229 (0.9%)	2
Hypotension	0/231 (0%)	0	1/229 (0.4%)	2
Thrombosis/thrombus/embolism	5/231 (2.2%)	5	0/229 (0%)	0

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.