Lenalidomide or Observation in Treating Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01169337
• Collaborator: (none)
• Enrollment: 226
• Locations: 613
• Arms: 2
• Anticipated Duration (Months): 197.8
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase II/III trial studies how well lenalidomide works and compares it to observation in treating patients with asymptomatic high-risk asymptomatic (smoldering) multiple myeloma. Biological therapies such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether lenalidomide is effective in treating patients with high-risk smoldering multiple myeloma than observation alone.

Condition or Disease	Intervention/Treatment	Phase
Light Chain Deposition Disease; Smoldering Plasma Cell Myeloma	Other: Clinical Observation; Drug: Lenalidomide	Phase 2/Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To study the risk of grade 3 adverse events that effect vital organ function (such as cardiac, hepatic or thromboembolic) or any grade 4 or higher non-hematologic adverse events among patients receiving lenalidomide as treatment for high-risk asymptomatic, smoldering multiple myeloma. (Phase II) II. To compare progression-free survival where failure is defined as death or the development of symptomatic myeloma indicating treatment between patients receiving lenalidomide versus observation alone in high-risk asymptomatic, smoldering multiple myeloma. (Phase III)

SECONDARY OBJECTIVES:

1. To assess the response to therapy of patients treated with lenalidomide as treatment for asymptomatic, smoldering multiple myeloma. (Phase II) II. To determine and compare the response rate, time to progression, 1-year progression-free survival probability, and overall survival between patients randomized to receive lenalidomide or observation in the setting of asymptomatic myeloma. (Phase III) III. To estimate the incidence of adverse events in patients receiving lenalidomide therapy for early-stage multiple myeloma. (Phase III)

CORRELATIVE OBJECTIVES:

1. To describe the cohort in terms of gene expression profiling (GEP) and cytogenetic risk classification and evaluate baseline immune and magnetic resonance imaging (MRI) parameters. (Phase II) II. To evaluate the impact of therapy within GEP-defined risk groups and GEP as a prognostic marker. (Phase III) III. To study the effects of lenalidomide on laboratory markers of immune function. (Phase III) IV. To study the prognostic value of MRI-detected asymptomatic bone disease on clinical outcome. (Phase III) V. To evaluate the prognostic effect of baseline high-risk cytogenetic abnormalities on clinical outcome. (Phase III)

QUALITY OF LIFE ASSESSMENT OBJECTIVES:

1. To compare quality of life (QOL) change between treatment and observation arms based on the functional (FWB) and physical (PWB) well-being components of the Functional Assessment of Cancer Therapy (FACT)-General (G) patient-reported outcome (PRO) measure from registration (prior to initiation of treatment) up to cycle 24.

2. To examine the impact of differential treatment response (PFS), if observed, on QOL based on the FACT FWB+PWB up to cycle 48.

3. To obtain prospective data on myeloma specific QOL attributes, utilizing and evaluating the Multiple Myeloma Subscale (MMS).

OUTLINE:

PHASE II (Arm A): Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE III: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo observation until progression to symptomatic myeloma.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 226 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase III Trial of Lenalidomide Versus Observation Alone in Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma
• Actual Study Start Date: Jan 24, 2011
• Actual Primary Completion Date: Jan 25, 2019
• Anticipated Study Completion Date: Jul 20, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (lenalidomide) Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Lenalidomide; Given PO; Other Names: CC-5013 CDC-501 Revlimid
Active Comparator: Arm B (observation) Patients undergo observation until progression to symptomatic myeloma.	Other: Clinical Observation; Undergo observation

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With Grade 3 Adverse Events That Effect Vital Organ Function or Any Grade 4 or Higher Non-hematologic Adverse Events (Phase II Primary Endpoint) [Assessed every 4 weeks while on treatment up to 24 weeks]

   Proportion of patients with grade 3 adverse events that effect vital organ function (such as cardiac, hepatic or thromboembolic) or any grade 4 or higher non-hematologic adverse events

2. 2-year Progression-free Survival (PFS) Rate (Phase III Primary Endpoint) [Assessed every 3 months for 2 years]

   PFS is defined as time from randomization to progression or death, whichever occurs first. Patients are considered to have progression if both of the following criteria are met. Kaplan-Meier method was used to estimate 2-year PFS rate. Any of the following: Increase in serum M-protein to ≥ 25% above the lowest response level with an absolute increase of at least 0.5g/dl to qualify as "progression" Increase in urine M-protein to ≥ 25% above the lowest response level for 24-hour excretion with an absolute increase of at least 200mg/24 hours of urine M-protein to qualify as "progression" Increase in bone marrow plasma cell percentage to ≥ 25% from lowest response value (the absolute % increase must be ≥ 10%) Any of the following felt related to the underlying clonal plasma cell proliferative disorder: Hypercalcemia (> 11 mg/dL) Decrease in hemoglobin of ≥ 2 gms/dL Serum creatinine level ≥ 2mg/dL Development of myeloma bone lesions or soft tissue plasmacytoma

Secondary Outcome Measures

1. Proportion of Participants With Response (Phase II Secondary Endpoint) [Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then annually for years 6-10]

   Response is defined as complete response (CR), very good partial response (VGPR) or partial response (PR). CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-component plus urine M-component < 100 mg per 24 hours PR: ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours If followed by free light chain (FLC) only, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels If unmeasurable disease by serum M-protein, urine M-protein, and serum FLC at baseline, a ≥50% reduction in plasma cells provided baseline bone marrow percentage was ≥ 30% If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas

2. Proportion of Participants With Response (Phase III Secondary Endpoint) [Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then annually for years 6-10]

   Response is defined as complete response (CR), very good partial response (VGPR) or partial response (PR). CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-component plus urine M-component < 100 mg per 24 hours PR: ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours If followed by free light chain (FLC) only, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels If unmeasurable disease by serum M-protein, urine M-protein, and serum FLC at baseline, a ≥50% reduction in plasma cells provided baseline bone marrow percentage was ≥ 30% If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas

3. 1-year Progression-free Survival (PFS) Rate (Phase III Secondary Endpoint) [Assessed every 3 months for one year]

   PFS is defined as time from randomization to progression or death, whichever occurs first. Patients are considered to have progression if both of the following criteria are met. Kaplan-Meier method was used to estimate 1-year PFS rate. Any of the following: Increase in serum M-protein to ≥ 25% above the lowest response level with an absolute increase of at least 0.5g/dl to qualify as "progression" Increase in urine M-protein to ≥ 25% above the lowest response level for 24-hour excretion with an absolute increase of at least 200mg/24 hours of urine M-protein to qualify as "progression" Increase in bone marrow plasma cell percentage to ≥ 25% from lowest response value (the absolute % increase must be ≥ 10%) Any of the following felt related to the underlying clonal plasma cell proliferative disorder: Hypercalcemia (> 11 mg/dL) Decrease in hemoglobin of ≥ 2 gms/dL Serum creatinine level ≥ 2mg/dL Development of myeloma bone lesions or soft tissue plasmacytoma

4. 2-year Progression-free Rate (Phase III Secondary Endpoint) [Assessed every 3 months for 2 years]

   TTP is defined as the time from randomization to progression. Patients are considered to have progression if both of the following criteria are met. Kaplan-Meier method was used to estimate 2-year progression-free rate. Any of the following: Increase in serum M-protein to ≥ 25% above the lowest response level with an absolute increase of at least 0.5g/dl to qualify as "progression" Increase in urine M-protein to ≥ 25% above the lowest response level for 24-hour excretion with an absolute increase of at least 200mg/24 hours of urine M-protein to qualify as "progression" Increase in bone marrow plasma cell percentage to ≥ 25% from lowest response value (the absolute % increase must be ≥ 10%) Any one or more of the following felt related to the underlying clonal plasma cell proliferative disorder: Hypercalcemia (> 11 mg/dL) Decrease in hemoglobin of ≥ 2 gms/dL Serum creatinine level ≥ 2mg/dL Development of myeloma bone lesions or soft tissue plasmacytoma

5. 2-year Overall Survival (OS) Rate (Phase III Secondary Endpoint) [Assessed every 3 months for 2 years]

   Overall survival is defined as the time from randomization to death or date last known alive among all randomized patients in the phase III part of the study. Kaplan-Meier method was used to estimate the 2-year OS rate.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must be diagnosed with asymptomatic high-risk smoldering multiple myeloma (SMM) within the past 60 months, as confirmed by both of the following:

• Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells at any time before initiating study treatment, including a marrow which must be obtained by bone marrow aspiration and/or biopsy within 4 weeks prior to randomization

• Abnormal serum free light chain ratio (< 0.26 or > 1.65) by serum free light chain (FLC) assay; FLC assay must be performed within 28 days of randomization

• Patients must have measurable levels of monoclonal protein (M-protein): >= 1g/dL on serum protein electrophoresis or >= 200 mg of monoclonal protein on a 24 hour urine protein electrophoresis which must be obtained within 4 weeks prior to randomization

• Hemoglobin >= 11 g/dL within four weeks prior to randomization

• Platelet count >= 100,000/mm^3 within four weeks prior to randomization

• Absolute neutrophil count (ANC) >= 1,500/mm^3 within four weeks prior to randomization

• Calculated creatinine clearance >= 30 mL/min within four weeks prior to randomization

• Bilirubin =< 1.5 mg/dL within four weeks prior to randomization

• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGPT) (aspartate aminotransferase [AST]) =< 2.5 times upper limit of normal within four weeks prior to randomization

• Prior systemic glucocorticosteroid use for the treatment of non-malignant disorders is permitted; concurrent use after registration on the study should be restricted to the equivalent of prednisone 10 mg per day

• Prior or concurrent topical or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is permitted

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

• Patients may have a history of current or previous deep vein thrombosis or pulmonary embolism but are required to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation

• Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for the time period considered appropriate for cure of the specific cancer; for most diseases this time frame is 5 years

• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting cycle 1 of lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure

• Human immunodeficiency virus (HIV) infection is not excluded; HIV+ patients must meet the following criteria:

• Cluster of differentiation (CD)4 cell count >= 350/mm^3

• No history of acquired immune deficiency syndrome (AIDS)-related illness

• Not currently prescribed zidovudine or stavudine

Exclusion Criteria:

• Lytic lesions on skeletal surveys or hypercalcemia (i.e., >= 11 mg/dL)

• Prior or concurrent systemic or radiation therapy for the treatment of myeloma

• Concurrent use of bisphosphonates; however, prior bisphosphonates or once-a-year intravenous bisphosphonate given for the treatment of osteoporosis is permitted

• Prior or concurrent use of erythropoietin

• Prior glucocorticosteroid therapy for the treatment of multiple myeloma

• Active, uncontrolled seizure disorder; patients must have had no seizures in the last 6 months

• Uncontrolled intercurrent illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would limit compliance with the study, or a prior history of Stevens Johnson syndrome

• Baseline bone lesions or plasmacytomas

• Monoclonal gammopathy of undetermined significance

• Grade 2 or higher peripheral neuropathy

• Active, uncontrolled infection

• New York Heart Association classification III or IV heart failure

• An immediate need for chemotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
2	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
3	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
4	Katmai Oncology Group	Anchorage	Alaska	United States	99508
5	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
6	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
7	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
8	Sutter Auburn Faith Hospital	Auburn	California	United States	95602
9	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
10	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
11	Mills-Peninsula Medical Center	Burlingame	California	United States	94010
12	Saint Jude Medical Center	Fullerton	California	United States	92835
13	Memorial Medical Center	Modesto	California	United States	95355
14	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
15	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California	United States	94040
16	Sutter Cancer Research Consortium	Novato	California	United States	94945
17	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
18	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
19	Eisenhower Medical Center	Rancho Mirage	California	United States	92270
20	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
21	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
22	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
23	UCSF Medical Center-Parnassus	San Francisco	California	United States	94143
24	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California	United States	95065
25	Sutter Pacific Medical Foundation	Santa Rosa	California	United States	95403
26	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California	United States	94086
27	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
28	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado	United States	80012
29	The Medical Center of Aurora	Aurora	Colorado	United States	80012
30	University of Colorado Hospital	Aurora	Colorado	United States	80045
31	Boulder Community Hospital	Boulder	Colorado	United States	80301
32	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado	United States	80304
33	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
34	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado	United States	80907
35	Denver Health Medical Center	Denver	Colorado	United States	80204
36	Porter Adventist Hospital	Denver	Colorado	United States	80210
37	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
38	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
39	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado	United States	80218
40	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
41	Rocky Mountain Cancer Centers-Rose	Denver	Colorado	United States	80220
42	Rose Medical Center	Denver	Colorado	United States	80220
43	Western States Cancer Research NCORP	Denver	Colorado	United States	80222
44	Mercy Medical Center	Durango	Colorado	United States	81301
45	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado	United States	80113
46	Swedish Medical Center	Englewood	Colorado	United States	80113
47	Mountain Blue Cancer Care Center	Golden	Colorado	United States	80401
48	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81501
49	North Colorado Medical Center	Greeley	Colorado	United States	80631
50	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado	United States	80111
51	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado	United States	80228
52	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
53	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado	United States	80120
54	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
55	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado	United States	80124
56	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
57	Longmont United Hospital	Longmont	Colorado	United States	80501
58	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado	United States	80501
59	McKee Medical Center	Loveland	Colorado	United States	80539
60	Parker Adventist Hospital	Parker	Colorado	United States	80138
61	Rocky Mountain Cancer Centers-Parker	Parker	Colorado	United States	80138
62	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
63	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado	United States	81008
64	North Suburban Medical Center	Thornton	Colorado	United States	80229
65	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado	United States	80260
66	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
67	Danbury Hospital	Danbury	Connecticut	United States	06810
68	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
69	Manchester Memorial Hospital	Manchester	Connecticut	United States	06040
70	Middlesex Hospital	Middletown	Connecticut	United States	06457
71	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
72	Yale University	New Haven	Connecticut	United States	06520
73	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
74	Beebe Medical Center	Lewes	Delaware	United States	19958
75	Christiana Gynecologic Oncology LLC	Newark	Delaware	United States	19713
76	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
77	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
78	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
79	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
80	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
81	Nanticoke Memorial Hospital	Seaford	Delaware	United States	19973
82	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
83	Kaiser Permanente-Capitol Hill Medical Center	Washington	District of Columbia	United States	20002
84	AdventHealth Altamonte	Altamonte Springs	Florida	United States	32701
85	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
86	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
87	Baptist MD Anderson Cancer Center	Jacksonville	Florida	United States	32207
88	Jupiter Medical Center	Jupiter	Florida	United States	33458
89	AdventHealth Kissimmee	Kissimmee	Florida	United States	34744
90	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
91	AdventHealth Orlando	Orlando	Florida	United States	32803
92	AdventHealth East Orlando	Orlando	Florida	United States	32822
93	Memorial Hospital West	Pembroke Pines	Florida	United States	33028
94	AdventHealth Winter Park	Winter Park	Florida	United States	32792
95	Phoebe Putney Memorial Hospital	Albany	Georgia	United States	31701
96	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
97	Northside Hospital	Atlanta	Georgia	United States	30342
98	Augusta University Medical Center	Augusta	Georgia	United States	30912
99	Atlanta VA Medical Center	Decatur	Georgia	United States	30033
100	Dekalb Medical Center	Decatur	Georgia	United States	30033
101	Medical Center of Central Georgia	Macon	Georgia	United States	31201
102	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
103	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
104	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
105	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho	United States	83619
106	Saint Joseph Regional Medical Center	Lewiston	Idaho	United States	83501
107	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho	United States	83642
108	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho	United States	83686
109	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
110	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho	United States	83301
111	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
112	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
113	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
114	Graham Hospital Association	Canton	Illinois	United States	61520
115	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
116	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
117	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
118	Memorial Hospital	Carthage	Illinois	United States	62321
119	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
120	University of Illinois	Chicago	Illinois	United States	60612
121	Advocate Illinois Masonic Medical Center	Chicago	Illinois	United States	60657
122	Carle on Vermilion	Danville	Illinois	United States	61832
123	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
124	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
125	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
126	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
127	Crossroads Cancer Center	Effingham	Illinois	United States	62401
128	Eureka Hospital	Eureka	Illinois	United States	61530
129	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
130	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
131	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
132	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois	United States	60134
133	Illinois CancerCare-Havana	Havana	Illinois	United States	62644
134	Mason District Hospital	Havana	Illinois	United States	62644
135	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
136	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
137	Mcdonough District Hospital	Macomb	Illinois	United States	61455
138	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
139	Loyola University Medical Center	Maywood	Illinois	United States	60153
140	Holy Family Medical Center	Monmouth	Illinois	United States	61462
141	Illinois CancerCare-Monmouth	Monmouth	Illinois	United States	61462
142	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
143	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
144	Community Cancer Center Foundation	Normal	Illinois	United States	61761
145	Illinois CancerCare-Community Cancer Center	Normal	Illinois	United States	61761
146	Cancer Care Center of O'Fallon	O'Fallon	Illinois	United States	62269
147	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
148	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
149	Radiation Oncology of Northern Illinois	Ottawa	Illinois	United States	61350
150	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
151	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
152	Proctor Hospital	Peoria	Illinois	United States	61614
153	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
154	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
155	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
156	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
157	Illinois Valley Hospital	Peru	Illinois	United States	61354
158	Valley Radiation Oncology	Peru	Illinois	United States	61354
159	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
160	Perry Memorial Hospital	Princeton	Illinois	United States	61356
161	Swedish American Hospital	Rockford	Illinois	United States	61104
162	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois	United States	61114
163	Illinois CancerCare-Spring Valley	Spring Valley	Illinois	United States	61362
164	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
165	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
166	Springfield Clinic	Springfield	Illinois	United States	62702
167	Memorial Medical Center	Springfield	Illinois	United States	62781
168	Carle Cancer Center	Urbana	Illinois	United States	61801
169	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
170	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois	United States	60555
171	Rush-Copley Healthcare Center	Yorkville	Illinois	United States	60560
172	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
173	IU Health Arnett Cancer Care	Lafayette	Indiana	United States	47904
174	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
175	Woodland Cancer Care Center	Michigan City	Indiana	United States	46360
176	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana	United States	46545
177	Reid Health	Richmond	Indiana	United States	47374
178	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
179	Porter Memorial Hospital	Valparaiso	Indiana	United States	46383
180	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
181	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa	United States	52722
182	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
183	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
184	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
185	Genesis Medical Center - East Campus	Davenport	Iowa	United States	52803
186	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
187	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
188	Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
189	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
190	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51102
191	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
192	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
193	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
194	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
195	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
196	Newman Regional Health	Emporia	Kansas	United States	66801
197	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
198	Saint Catherine Hospital	Garden City	Kansas	United States	67846
199	Saint Rose Ambulatory and Surgery Center	Great Bend	Kansas	United States	67530
200	HaysMed University of Kansas Health System	Hays	Kansas	United States	67601
201	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
202	University of Kansas Cancer Center-West	Kansas City	Kansas	United States	66112
203	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
204	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
205	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
206	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
207	Cancer Center of Kansas-Manhattan	Manhattan	Kansas	United States	66502
208	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
209	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
210	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas	United States	66210
211	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
212	Ascension Via Christi - Pittsburg	Pittsburg	Kansas	United States	66762
213	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
214	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
215	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
216	Salina Regional Health Center	Salina	Kansas	United States	67401
217	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas	United States	66606
218	University of Kansas Health System Saint Francis Campus	Topeka	Kansas	United States	66606
219	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
220	Associates In Womens Health	Wichita	Kansas	United States	67208
221	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
222	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
223	Wesley Medical Center	Wichita	Kansas	United States	67214
224	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
225	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
226	Flaget Memorial Hospital	Bardstown	Kentucky	United States	40004
227	Jewish Hospital	Louisville	Kentucky	United States	40202
228	Saints Mary and Elizabeth Hospital	Louisville	Kentucky	United States	40215
229	Jewish Hospital Medical Center Northeast	Louisville	Kentucky	United States	40245
230	Baton Rouge General Medical Center	Baton Rouge	Louisiana	United States	70806
231	Hematology/Oncology Clinic PLLC	Baton Rouge	Louisiana	United States	70809
232	Ochsner Health Center-Summa	Baton Rouge	Louisiana	United States	70809
233	Ochsner Health Center-Covington	Covington	Louisiana	United States	70433
234	Ochsner Medical Center Kenner	Kenner	Louisiana	United States	70065
235	Ochsner LSU Health Monroe Medical Center	Monroe	Louisiana	United States	71202
236	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
237	Ochsner Baptist Medical Center	New Orleans	Louisiana	United States	70115
238	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
239	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana	United States	71103
240	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
241	Eastern Maine Medical Center	Bangor	Maine	United States	04401
242	Lafayette Family Cancer Center-EMMC	Brewer	Maine	United States	04412
243	York Hospital	York	Maine	United States	03909
244	Kaiser Permanente-Woodlawn Medical Center	Baltimore	Maryland	United States	21244
245	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
246	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
247	Frederick Memorial Hospital	Frederick	Maryland	United States	21701
248	Kaiser Permanente-Gaithersburg Medical Center	Gaithersburg	Maryland	United States	20879
249	Kaiser Permanente - Largo Medical Center	Largo	Maryland	United States	20774
250	Beverly Hospital	Beverly	Massachusetts	United States	01915
251	Tufts Medical Center	Boston	Massachusetts	United States	02111
252	Steward Saint Elizabeth's Medical Center	Brighton	Massachusetts	United States	02135
253	Addison Gilbert Hospital	Gloucester	Massachusetts	United States	01930
254	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts	United States	01655
255	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
256	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
257	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
258	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
259	Henry Ford Hospital	Detroit	Michigan	United States	48202
260	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
261	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan	United States	48054
262	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
263	Weisberg Cancer Treatment Center	Farmington Hills	Michigan	United States	48334
264	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
265	Hurley Medical Center	Flint	Michigan	United States	48503
266	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
267	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan	United States	48236
268	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan	United States	48236
269	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan	United States	48236
270	Allegiance Health	Jackson	Michigan	United States	49201
271	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
272	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
273	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
274	Sparrow Hospital	Lansing	Michigan	United States	48912
275	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
276	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan	United States	48044
277	Michigan Breast Specialists-Macomb Township	Macomb	Michigan	United States	48044
278	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
279	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
280	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan	United States	48309
281	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
282	Ascension Providence Hospitals - Southfield	Southfield	Michigan	United States	48075
283	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan	United States	48312
284	Advanced Breast Care Center PLLC	Warren	Michigan	United States	48088
285	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan	United States	48093
286	Macomb Hematology Oncology PC	Warren	Michigan	United States	48093
287	Michigan Breast Specialists-Warren	Warren	Michigan	United States	48093
288	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
289	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota	United States	56401
290	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
291	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
292	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
293	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
294	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
295	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
296	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota	United States	56537
297	Unity Hospital	Fridley	Minnesota	United States	55432
298	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
299	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
300	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
301	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
302	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
303	Health Partners Inc	Minneapolis	Minnesota	United States	55454
304	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
305	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
306	Mayo Clinic	Rochester	Minnesota	United States	55905
307	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
308	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
309	Regions Hospital	Saint Paul	Minnesota	United States	55101
310	United Hospital	Saint Paul	Minnesota	United States	55102
311	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
312	Lakeview Hospital	Stillwater	Minnesota	United States	55082
313	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
314	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
315	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
316	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
317	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
318	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri	United States	63628
319	Cox Cancer Center Branson	Branson	Missouri	United States	65616
320	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
321	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
322	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
323	Freeman Health System	Joplin	Missouri	United States	64804
324	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
325	Truman Medical Centers	Kansas City	Missouri	United States	64108
326	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
327	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri	United States	64128
328	The University of Kansas Cancer Center-South	Kansas City	Missouri	United States	64131
329	University of Kansas Cancer Center - North	Kansas City	Missouri	United States	64154
330	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri	United States	64064
331	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
332	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
333	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
334	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
335	Comprehensive Cancer Care PC	Saint Louis	Missouri	United States	63141
336	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
337	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
338	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
339	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
340	CoxHealth South Hospital	Springfield	Missouri	United States	65807
341	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
342	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
343	Billings Clinic Cancer Center	Billings	Montana	United States	59101
344	Saint Vincent Healthcare	Billings	Montana	United States	59101
345	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
346	Saint Vincent Frontier Cancer Center	Billings	Montana	United States	59102
347	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
348	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
349	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
350	Great Falls Clinic	Great Falls	Montana	United States	59405
351	Northern Montana Hospital	Havre	Montana	United States	59501
352	Saint Peter's Community Hospital	Helena	Montana	United States	59601
353	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
354	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
355	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
356	Montana Cancer Specialists	Missoula	Montana	United States	59802
357	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
358	Community Medical Hospital	Missoula	Montana	United States	59804
359	CHI Health Saint Francis	Grand Island	Nebraska	United States	68803
360	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
361	Nebraska Hematology and Oncology	Lincoln	Nebraska	United States	68506
362	Nebraska Cancer Research Center	Lincoln	Nebraska	United States	68510
363	Southeast Nebraska Cancer Center - 68th Street Place	Lincoln	Nebraska	United States	68516
364	Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
365	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
366	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
367	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
368	Creighton University Medical Center	Omaha	Nebraska	United States	68131
369	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
370	Carson Tahoe Regional Medical Center	Carson City	Nevada	United States	89703
371	Cancer and Blood Specialists-Henderson	Henderson	Nevada	United States	89052
372	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada	United States	89052
373	Las Vegas Cancer Center-Henderson	Henderson	Nevada	United States	89052
374	21st Century Oncology-Henderson	Henderson	Nevada	United States	89074
375	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada	United States	89074
376	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
377	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada	United States	89106
378	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
379	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada	United States	89106
380	21st Century Oncology	Las Vegas	Nevada	United States	89109
381	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada	United States	89109
382	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada	United States	89113
383	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada	United States	89119
384	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada	United States	89121
385	21st Century Oncology-Vegas Tenaya	Las Vegas	Nevada	United States	89128
386	Ann M Wierman MD LTD	Las Vegas	Nevada	United States	89128
387	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada	United States	89128
388	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada	United States	89128
389	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada	United States	89128
390	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada	United States	89144
391	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
392	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada	United States	89148-2405
393	21st Century Oncology-Fort Apache	Las Vegas	Nevada	United States	89148
394	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89148
395	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada	United States	89148
396	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada	United States	89149
397	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada	United States	89169
398	University Cancer Center	Las Vegas	Nevada	United States	89169
399	Renown Regional Medical Center	Reno	Nevada	United States	89502
400	Saint Mary's Regional Medical Center	Reno	Nevada	United States	89503
401	Radiation Oncology Associates	Reno	Nevada	United States	89509
402	Cancer Care Specialists - Reno	Reno	Nevada	United States	89511
403	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
404	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey	United States	07018-1095
405	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
406	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
407	Saint Joseph's Regional Medical Center	Paterson	New Jersey	United States	07503
408	Inspira Medical Center Vineland	Vineland	New Jersey	United States	08360
409	Inspira Medical Center Woodbury	Woodbury	New Jersey	United States	08096
410	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
411	Presbyterian Kaseman Hospital	Albuquerque	New Mexico	United States	87110
412	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
413	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
414	Orange Regional Medical Center	Middletown	New York	United States	10940
415	Champlain Valley Physicians Hospital Medical Center	Plattsburgh	New York	United States	12901
416	Dickstein Cancer Treatment Center	White Plains	New York	United States	10601
417	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina	United States	28328
418	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina	United States	27534
419	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
420	East Carolina University	Greenville	North Carolina	United States	27834
421	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina	United States	28546
422	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
423	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
424	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina	United States	27104
425	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
426	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
427	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
428	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
429	Altru Cancer Center	Grand Forks	North Dakota	United States	58201
430	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
431	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
432	Mercy Medical Center	Canton	Ohio	United States	44708
433	Geauga Hospital	Chardon	Ohio	United States	44024
434	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
435	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
436	TriHealth Cancer Institute-Westside	Cincinnati	Ohio	United States	45247
437	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio	United States	45255
438	Case Western Reserve University	Cleveland	Ohio	United States	44106
439	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
440	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
441	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
442	Columbus NCI Community Oncology Research Program	Columbus	Ohio	United States	43215
443	Grant Medical Center	Columbus	Ohio	United States	43215
444	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
445	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
446	Doctors Hospital	Columbus	Ohio	United States	43228
447	Grandview Hospital	Dayton	Ohio	United States	45405
448	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
449	Miami Valley Hospital	Dayton	Ohio	United States	45409
450	Miami Valley Hospital North	Dayton	Ohio	United States	45415
451	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
452	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
453	Grady Memorial Hospital	Delaware	Ohio	United States	43015
454	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
455	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
456	Wayne Hospital	Greenville	Ohio	United States	45331
457	Kettering Medical Center	Kettering	Ohio	United States	45429
458	Fairfield Medical Center	Lancaster	Ohio	United States	43130
459	Lancaster Radiation Oncology	Lancaster	Ohio	United States	43130
460	Saint Rita's Medical Center	Lima	Ohio	United States	45801
461	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
462	UH Seidman Cancer Center at Landerbrook Health Center	Mayfield Heights	Ohio	United States	44124
463	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
464	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
465	Licking Memorial Hospital	Newark	Ohio	United States	43055
466	Newark Radiation Oncology	Newark	Ohio	United States	43055
467	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
468	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
469	Springfield Regional Cancer Center	Springfield	Ohio	United States	45504
470	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
471	ProMedica Flower Hospital	Sylvania	Ohio	United States	43560
472	Upper Valley Medical Center	Troy	Ohio	United States	45373
473	Saint Ann's Hospital	Westerville	Ohio	United States	43081
474	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio	United States	44145
475	UHHS-Westlake Medical Center	Westlake	Ohio	United States	44145
476	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
477	Greene Memorial Hospital	Xenia	Ohio	United States	45385
478	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
479	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
480	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
481	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon	United States	97015
482	Bay Area Hospital	Coos Bay	Oregon	United States	97420
483	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
484	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
485	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
486	Providence Portland Medical Center	Portland	Oregon	United States	97213
487	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
488	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
489	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania	United States	18015
490	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
491	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
492	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
493	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
494	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania	United States	17837
495	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
496	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107
497	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
498	West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224
499	Pottstown Hospital	Pottstown	Pennsylvania	United States	19464
500	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania	United States	17901
501	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
502	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania	United States	17870
503	Geisinger Medical Group	State College	Pennsylvania	United States	16801
504	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
505	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
506	UPMC Susquehanna	Williamsport	Pennsylvania	United States	17701
507	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
508	Roper Hospital	Charleston	South Carolina	United States	29401
509	Charleston Oncology - Roper	Charleston	South Carolina	United States	29403
510	Charleston Oncology - Saint Francis	Charleston	South Carolina	United States	29414
511	Medical University of South Carolina	Charleston	South Carolina	United States	29425
512	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
513	Saint Francis Hospital	Greenville	South Carolina	United States	29601
514	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
515	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
516	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
517	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
518	Self Regional Healthcare	Greenwood	South Carolina	United States	29646
519	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
520	Lowcountry Hematology Oncology PA-Mount Pleasant	Mount Pleasant	South Carolina	United States	29464
521	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
522	Prisma Health Cancer Institute - Spartanburg	Spartanburg	South Carolina	United States	29307
523	Avera Cancer Institute-Aberdeen	Aberdeen	South Dakota	United States	57401
524	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
525	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
526	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota	United States	57105
527	Jackson-Madison County General Hospital	Jackson	Tennessee	United States	38301
528	Regional Cancer Center at Indian Path Community Hospital	Kingsport	Tennessee	United States	37660
529	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
530	University of Tennessee - Knoxville	Knoxville	Tennessee	United States	37920
531	Parkland Memorial Hospital	Dallas	Texas	United States	75235
532	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
533	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas	United States	76104
534	Covenant Medical Center-Lakeside	Lubbock	Texas	United States	79410
535	Rutland Regional Medical Center	Rutland	Vermont	United States	05701
536	Kaiser Permanente-Burke Medical Center	Burke	Virginia	United States	22015
537	Danville Regional Medical Center	Danville	Virginia	United States	24541
538	Kaiser Permanente Tysons Corner Medical Center	McLean	Virginia	United States	22102
539	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
540	MultiCare Auburn Medical Center	Auburn	Washington	United States	98001
541	Overlake Hospital Medical Center	Bellevue	Washington	United States	98004
542	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
543	Swedish Cancer Institute-Edmonds	Edmonds	Washington	United States	98026
544	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
545	Saint Francis Hospital	Federal Way	Washington	United States	98003
546	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
547	Providence Regional Cancer System-Lacey	Lacey	Washington	United States	98503
548	Saint Clare Hospital	Lakewood	Washington	United States	98499
549	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
550	Providence - Saint Peter Hospital	Olympia	Washington	United States	98506-5166
551	Capital Medical Center	Olympia	Washington	United States	98507
552	MultiCare Good Samaritan Hospital	Puyallup	Washington	United States	98372
553	Swedish Medical Center-Ballard Campus	Seattle	Washington	United States	98107
554	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
555	MultiCare Allenmore Hospital	Tacoma	Washington	United States	98405
556	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
557	Northwest Medical Specialties PLLC	Tacoma	Washington	United States	98405
558	Northwest NCI Community Oncology Research Program	Tacoma	Washington	United States	98405
559	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
560	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
561	Compass Oncology Vancouver	Vancouver	Washington	United States	98684
562	West Virginia University Charleston Division	Charleston	West Virginia	United States	25304
563	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
564	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
565	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
566	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
567	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
568	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
569	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
570	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
571	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
572	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
573	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
574	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
575	Dean Hematology and Oncology Clinic	Madison	Wisconsin	United States	53717
576	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
577	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
578	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin	United States	54143
579	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
580	Ascension Columbia Saint Mary's Hospital Ozaukee	Mequon	Wisconsin	United States	53097
581	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
582	Ascension Columbia Saint Mary's Hospital - Milwaukee	Milwaukee	Wisconsin	United States	53211
583	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
584	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
585	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
586	ProHealth D N Greenwald Center	Mukwonago	Wisconsin	United States	53149
587	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
588	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
589	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin	United States	54154
590	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
591	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
592	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
593	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin	United States	54868
594	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
595	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
596	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235-1495
597	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
598	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
599	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
600	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin	United States	53188
601	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin	United States	53188
602	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin	United States	53188
603	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
604	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
605	Diagnostic and Treatment Center	Weston	Wisconsin	United States	54476
606	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
607	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
608	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
609	Welch Cancer Center	Sheridan	Wyoming	United States	82801
610	Mater Misericordiae University Hospital	Dublin	Co Dublin	Ireland	7
611	Mater Private Hospital	Dublin	Co Dublin	Ireland	7
612	University College Hospital Galway	Galway	Co Galway	Ireland
613	Fundacion De Investigacion de Diego	San Juan		Puerto Rico	00927

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Sagar Lonial, ECOG-ACRIN Cancer Research Group

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 26, 2019

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01169337
• Other Study ID Numbers: NCI-2011-02057; NCI-2011-02057; E3A06; E3A06; U10CA180820; U10CA021115; U24CA196172
• First Posted: Jul 26, 2010
• Last Update Posted: May 18, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Cancer Institute (NCI): Lenalidomide; Smoldering Multiple Myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Lenalidomide

Study Results

Participant Flow

Recruitment Details	Between January 2011 and January 2013, 44 patients were enrolled in the phase II safety run in portion of the study and were treated with lenalidomide as a single agent. Between February 2013 and July 2017, 182 patients were randomly assigned between the two treatment arms in the phase III portion of the study.

Arm/Group Title	Arm A (Lenalidomide; Phase II)	Arm A (Lenalidomide; Phase III)	Arm B (Observation; Phase III)
Arm/Group Description	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients undergo observation until progression to symptomatic myeloma.
Period Title: Overall Study
STARTED	44	90	92
Received Treatment/Observation	44	88	86
COMPLETED	0	0	86
NOT COMPLETED	44	90	6

Baseline Characteristics

Arm/Group Title	Arm A (Lenalidomide; Phase II)	Arm A (Lenalidomide; Phase III)	Arm B (Observation; Phase III)	Total
Arm/Group Description	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients undergo observation until progression to symptomatic myeloma.	Total of all reporting groups
Overall Participants	44	90	92	226
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	63	64	64
Sex: Female, Male (Count of Participants)
Female	24 54.5%	48 53.3%	46 50%	118 52.2%
Male	20 45.5%	42 46.7%	46 50%	108 47.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 2.2%	4 4.3%	6 2.7%
Not Hispanic or Latino	43 97.7%	81 90%	81 88%	205 90.7%
Unknown or Not Reported	1 2.3%	7 7.8%	7 7.6%	15 6.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 1.1%	1 1.1%	2 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	6 13.6%	12 13.3%	19 20.7%	37 16.4%
White	37 84.1%	72 80%	68 73.9%	177 78.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.3%	5 5.6%	4 4.3%	10 4.4%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With Grade 3 Adverse Events That Effect Vital Organ Function or Any Grade 4 or Higher Non-hematologic Adverse Events (Phase II Primary Endpoint)
Description	Proportion of patients with grade 3 adverse events that effect vital organ function (such as cardiac, hepatic or thromboembolic) or any grade 4 or higher non-hematologic adverse events
Time Frame	Assessed every 4 weeks while on treatment up to 24 weeks

Outcome Measure Data

Analysis Population Description

The first 36 patients in the phase II part as planned in the study design

Arm/Group Title	Arm A (Lenalidomide; Phase II)
Arm/Group Description	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	36
Number (90% Confidence Interval) [proportion of participants]	0.056 0.1%

2. Primary Outcome

Title	2-year Progression-free Survival (PFS) Rate (Phase III Primary Endpoint)
Description	PFS is defined as time from randomization to progression or death, whichever occurs first. Patients are considered to have progression if both of the following criteria are met. Kaplan-Meier method was used to estimate 2-year PFS rate. Any of the following: Increase in serum M-protein to ≥ 25% above the lowest response level with an absolute increase of at least 0.5g/dl to qualify as "progression" Increase in urine M-protein to ≥ 25% above the lowest response level for 24-hour excretion with an absolute increase of at least 200mg/24 hours of urine M-protein to qualify as "progression" Increase in bone marrow plasma cell percentage to ≥ 25% from lowest response value (the absolute % increase must be ≥ 10%) Any of the following felt related to the underlying clonal plasma cell proliferative disorder: Hypercalcemia (> 11 mg/dL) Decrease in hemoglobin of ≥ 2 gms/dL Serum creatinine level ≥ 2mg/dL Development of myeloma bone lesions or soft tissue plasmacytoma
Time Frame	Assessed every 3 months for 2 years

Outcome Measure Data

Analysis Population Description

All randomized patients

Arm/Group Title	Arm A (Lenalidomide; Phase III)	Arm B (Observation; Phase III)
Arm/Group Description	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients undergo observation until progression to symptomatic myeloma.
Measure Participants	90	92
Number (95% Confidence Interval) [proportion of participants]	0.93 2.1%	0.76 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Lenalidomide; Phase II), Arm B (Observation; Phase III)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Log Rank
	Comments	stratified 1-sided log-rank test

3. Secondary Outcome

Title	Proportion of Participants With Response (Phase II Secondary Endpoint)
Description	Response is defined as complete response (CR), very good partial response (VGPR) or partial response (PR). CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-component plus urine M-component < 100 mg per 24 hours PR: ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours If followed by free light chain (FLC) only, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels If unmeasurable disease by serum M-protein, urine M-protein, and serum FLC at baseline, a ≥50% reduction in plasma cells provided baseline bone marrow percentage was ≥ 30% If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas
Time Frame	Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then annually for years 6-10

Outcome Measure Data

Analysis Population Description

All registered patients in the phase II part

Arm/Group Title	Arm A (Lenalidomide; Phase II)
Arm/Group Description	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	44
Number (95% Confidence Interval) [proportion of participants]	0.477 1.1%

4. Secondary Outcome

Title	Proportion of Participants With Response (Phase III Secondary Endpoint)
Description	Response is defined as complete response (CR), very good partial response (VGPR) or partial response (PR). CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-component plus urine M-component < 100 mg per 24 hours PR: ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours If followed by free light chain (FLC) only, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels If unmeasurable disease by serum M-protein, urine M-protein, and serum FLC at baseline, a ≥50% reduction in plasma cells provided baseline bone marrow percentage was ≥ 30% If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas
Time Frame	Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then annually for years 6-10

Outcome Measure Data

Analysis Population Description

Among randomized patients who received treatment or observation

Arm/Group Title	Arm A (Lenalidomide; Phase III)	Arm B (Observation; Phase III)
Arm/Group Description	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients undergo observation until progression to symptomatic myeloma.
Measure Participants	88	86
Number (95% Confidence Interval) [proportion of participants]	0.50 1.1%	0 0%

5. Secondary Outcome

Title	1-year Progression-free Survival (PFS) Rate (Phase III Secondary Endpoint)
Description	PFS is defined as time from randomization to progression or death, whichever occurs first. Patients are considered to have progression if both of the following criteria are met. Kaplan-Meier method was used to estimate 1-year PFS rate. Any of the following: Increase in serum M-protein to ≥ 25% above the lowest response level with an absolute increase of at least 0.5g/dl to qualify as "progression" Increase in urine M-protein to ≥ 25% above the lowest response level for 24-hour excretion with an absolute increase of at least 200mg/24 hours of urine M-protein to qualify as "progression" Increase in bone marrow plasma cell percentage to ≥ 25% from lowest response value (the absolute % increase must be ≥ 10%) Any of the following felt related to the underlying clonal plasma cell proliferative disorder: Hypercalcemia (> 11 mg/dL) Decrease in hemoglobin of ≥ 2 gms/dL Serum creatinine level ≥ 2mg/dL Development of myeloma bone lesions or soft tissue plasmacytoma
Time Frame	Assessed every 3 months for one year

Outcome Measure Data

Analysis Population Description

All randomized patients

Arm/Group Title	Arm A (Lenalidomide; Phase III)	Arm B (Observation; Phase III)
Arm/Group Description	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients undergo observation until progression to symptomatic myeloma.
Measure Participants	90	92
Number (95% Confidence Interval) [proportion of participants]	0.98 2.2%	0.89 1%

6. Secondary Outcome

Title	2-year Progression-free Rate (Phase III Secondary Endpoint)
Description	TTP is defined as the time from randomization to progression. Patients are considered to have progression if both of the following criteria are met. Kaplan-Meier method was used to estimate 2-year progression-free rate. Any of the following: Increase in serum M-protein to ≥ 25% above the lowest response level with an absolute increase of at least 0.5g/dl to qualify as "progression" Increase in urine M-protein to ≥ 25% above the lowest response level for 24-hour excretion with an absolute increase of at least 200mg/24 hours of urine M-protein to qualify as "progression" Increase in bone marrow plasma cell percentage to ≥ 25% from lowest response value (the absolute % increase must be ≥ 10%) Any one or more of the following felt related to the underlying clonal plasma cell proliferative disorder: Hypercalcemia (> 11 mg/dL) Decrease in hemoglobin of ≥ 2 gms/dL Serum creatinine level ≥ 2mg/dL Development of myeloma bone lesions or soft tissue plasmacytoma
Time Frame	Assessed every 3 months for 2 years

Outcome Measure Data

Analysis Population Description

All randomized patients in the phase III part of the study

Arm/Group Title	Arm A (Lenalidomide; Phase III)	Arm B (Observation; Phase III)
Arm/Group Description	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients undergo observation until progression to symptomatic myeloma.
Measure Participants	90	92
Number (95% Confidence Interval) [proportion of participants]	94.3 214.3%	75.8 84.2%

7. Secondary Outcome

Title	2-year Overall Survival (OS) Rate (Phase III Secondary Endpoint)
Description	Overall survival is defined as the time from randomization to death or date last known alive among all randomized patients in the phase III part of the study. Kaplan-Meier method was used to estimate the 2-year OS rate.
Time Frame	Assessed every 3 months for 2 years

Outcome Measure Data

Analysis Population Description

All randomized patients in the phase III part of the study

Arm/Group Title	Arm A (Lenalidomide; Phase III)	Arm B (Observation; Phase III)
Arm/Group Description	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients undergo observation until progression to symptomatic myeloma.
Measure Participants	90	92
Number (95% Confidence Interval) [proportion of participants]	0.98 2.2%	1.00 1.1%

Adverse Events

Time Frame	Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 10 years
Adverse Event Reporting Description	Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in serious adverse events. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Arm/Group Title	Arm A (Lenalidomide; Phase II)		Arm A (Lenalidomide; Phase III)		Arm B (Observation; Phase III)
Arm/Group Description	Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.		Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.		Patients undergo observation until progression to symptomatic myeloma.
All Cause Mortality
	Arm A (Lenalidomide; Phase II)		Arm A (Lenalidomide; Phase III)		Arm B (Observation; Phase III)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/44 (15.9%)		2/90 (2.2%)		4/92 (4.3%)
Serious Adverse Events
	Arm A (Lenalidomide; Phase II)		Arm A (Lenalidomide; Phase III)		Arm B (Observation; Phase III)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/44 (52.3%)		40/88 (45.5%)		8/86 (9.3%)
Blood and lymphatic system disorders
Febrile neutropenia	0/44 (0%)		2/88 (2.3%)		0/86 (0%)
Blood and lymphatic disorders - Other	0/44 (0%)		1/88 (1.1%)		0/86 (0%)
Cardiac disorders
Myocardial infarction	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Ear and labyrinth disorders
Hearing impaired	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Vertigo	0/44 (0%)		1/88 (1.1%)		0/86 (0%)
Gastrointestinal disorders
Constipation	0/44 (0%)		1/88 (1.1%)		0/86 (0%)
Diarrhea	1/44 (2.3%)		3/88 (3.4%)		1/86 (1.2%)
Vomiting	0/44 (0%)		1/88 (1.1%)		0/86 (0%)
Gastrointestinal disorders - Other	0/44 (0%)		1/88 (1.1%)		0/86 (0%)
General disorders
Fatigue	5/44 (11.4%)		5/88 (5.7%)		0/86 (0%)
Hepatobiliary disorders
Cholecystitis	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Immune system disorders
Allergic reaction	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Infections and infestations
Lung infection	1/44 (2.3%)		1/88 (1.1%)		0/86 (0%)
Sepsis	2/44 (4.5%)		0/88 (0%)		0/86 (0%)
Skin infection	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Investigations
Creatinine increased	0/44 (0%)		0/88 (0%)		1/86 (1.2%)
Lymphocyte count decreased	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Neutrophil count decreased	7/44 (15.9%)		12/88 (13.6%)		1/86 (1.2%)
Platelet count decreased	0/44 (0%)		1/88 (1.1%)		0/86 (0%)
Weight loss	1/44 (2.3%)		1/88 (1.1%)		0/86 (0%)
White blood cell decreased	1/44 (2.3%)		1/88 (1.1%)		0/86 (0%)
Metabolism and nutrition disorders
Dehydration	1/44 (2.3%)		1/88 (1.1%)		0/86 (0%)
Hypokalemia	2/44 (4.5%)		0/88 (0%)		0/86 (0%)
Hyponatremia	0/44 (0%)		0/88 (0%)		2/86 (2.3%)
Musculoskeletal and connective tissue disorders
Back pain	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Myalgia	0/44 (0%)		2/88 (2.3%)		0/86 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy	0/44 (0%)		2/88 (2.3%)		0/86 (0%)
Nervous system disorders
Ataxia	0/44 (0%)		1/88 (1.1%)		0/86 (0%)
Dizziness	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Headache	2/44 (4.5%)		0/88 (0%)		0/86 (0%)
Paresthesia	0/44 (0%)		0/88 (0%)		1/86 (1.2%)
Peripheral motor neuropathy	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Peripheral sensory neuropathy	1/44 (2.3%)		2/88 (2.3%)		0/86 (0%)
Syncope	0/44 (0%)		1/88 (1.1%)		0/86 (0%)
Nervous system disorders - Other	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Psychiatric disorders
Confusion	0/44 (0%)		1/88 (1.1%)		0/86 (0%)
Insomnia	0/44 (0%)		1/88 (1.1%)		0/86 (0%)
Renal and urinary disorders
Acute kidney injury	0/44 (0%)		0/88 (0%)		1/86 (1.2%)
Chronic kidney disease	0/44 (0%)		0/88 (0%)		1/86 (1.2%)
Renal and urinary disorders - Other	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/44 (0%)		3/88 (3.4%)		0/86 (0%)
Skin and subcutaneous tissue disorders
Erythroderma	0/44 (0%)		1/88 (1.1%)		0/86 (0%)
Pruritus	1/44 (2.3%)		0/88 (0%)		0/86 (0%)
Rash maculo-papular	2/44 (4.5%)		2/88 (2.3%)		0/86 (0%)
Vascular disorders
Hypertension	0/44 (0%)		1/88 (1.1%)		2/86 (2.3%)
Thromboembolic event	2/44 (4.5%)		1/88 (1.1%)		0/86 (0%)
Other (Not Including Serious) Adverse Events
	Arm A (Lenalidomide; Phase II)		Arm A (Lenalidomide; Phase III)		Arm B (Observation; Phase III)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/44 (31.8%)		20/88 (22.7%)		5/86 (5.8%)
Blood and lymphatic system disorders
Anemia	6/44 (13.6%)		5/88 (5.7%)		2/86 (2.3%)
Gastrointestinal disorders
Constipation	2/44 (4.5%)		7/88 (8%)		1/86 (1.2%)
General disorders
Fatigue	4/44 (9.1%)		9/88 (10.2%)		2/86 (2.3%)
Investigations
Lymphocyte count decreased	3/44 (6.8%)		4/88 (4.5%)		2/86 (2.3%)
Neutrophil count decreased	5/44 (11.4%)		8/88 (9.1%)		1/86 (1.2%)
Platelet count decreased	5/44 (11.4%)		5/88 (5.7%)		1/86 (1.2%)
White blood cell decreased	6/44 (13.6%)		9/88 (10.2%)		2/86 (2.3%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	4/44 (9.1%)		1/88 (1.1%)		1/86 (1.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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