A Study to Evaluate the Efficacy and Safety of Lenalidomide as Maintenance Therapy for Patients With B-Cell Chronic Lymphocytic Leukemia (CLL) Following Second Line Therapy

• Sponsor: Celgene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00774345
• Collaborator: (none)
• Enrollment: 317
• Locations: 241
• Arms: 2
• Actual Duration (Months): 141
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if lenalidomide (Revlimid®) is safe and effective as a maintenance therapy at improving further the quality of the response you achieved with your last therapy and at prolonging the duration of your response. This study will compare the effects (good and bad) of lenalidomide with the dummy drug.

Condition or Disease	Intervention/Treatment	Phase
B-cell Chronic Lymphocytic Leukemia	Drug: Lenalidomide; Drug: Placebo	Phase 3

Detailed Description

This is a phase 3, randomized (computer assigned by chance to treatment arm), study being completed an multiple sites to compare the safety and efficacy (how well a drug works) of lenalidomide maintenance therapy to placebo (dummy capsule that contains no lenalidomide or active substances) maintenance therapy.

Patients are assigned by a computer with a 50/50 chance to receive placebo or lenalidomide study treatment. Study drug will be taken once each day until the patient discontinues the study. Patients will remain on study drug until progression of disease.

Patients will visit their study doctor every 28 days until disease progression to complete safety and efficacy assessments. Quality of life assessments will be completed every other month. If a patient who discontinue study drug prior to disease progression (i.e. due to an adverse reaction to the study drug), they will continue to visit the study doctor each month to complete the efficacy assessments up to progression of disease. Safety assessments may include laboratory blood tests, ECG tests and questions about any medical conditions or side effects experienced during the study. Efficacy assessments may include laboratory blood tests and focused physical exams.

Computed tomography (CT) scans along with blood tests and bone marrow samples will be collected to confirm if a patient has improvement of response while on study.

After disease progression, patients will be contacted every 12 weeks for survival information, next CLL treatments and quality of life questions.

Subjects currently on lenalidomide treatment will discontinue lenalidomide treatment immediately and complete the Treatment Discontinuation assessment. The subjects will then transition to the survival follow-up period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 317 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Efficacy and Safety of Lenalidomide (Revlimid®) as Maintenance Therapy for Patients With B-Cell Chronic Lymphocytic Leukemia Following Second-Line Therapy (The Continuum Trial)
• Actual Study Start Date: Jan 27, 2009
• Actual Primary Completion Date: Oct 27, 2020
• Actual Study Completion Date: Oct 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: 1 Lenalidomide po qd on days 1-28 of a 28 day cycle	Drug: Lenalidomide; Lenalidomide capsules given orally on days 1-28 of a 28 day cycle; Other Names: Revlimid
Placebo Comparator: Placebo Comparator: 2 Placebo capsules given orally on days 1-28 of a 28 day cycle	Drug: Placebo; Placebo capsules given orally on days 1 - 28 of a 28 day cycle

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Up to approximately 11 years]

   Overall Survival (OS) is defined as the time from randomization to death from any cause. OS will be censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.

Secondary Outcome Measures

1. Progression Free Survival 2 (PFS2) [Up to 6 years]

   Progression Free Survival (PFS2) assessed by investigator is defined as the time from randomization to the second objective disease progression, or death from any cause, whichever occurs first.

2. Number of Participants With Adverse Events (AEs) [From first dose to 30 days post last dose (up to 9 years)]

   Number of participants with adverse events (AEs) that measure type, frequency and severity of AEs graded by National Cancer Institute Common Terminology Criteria (NCI CTCAE V 3.0) including any grade adverse events (AEs), Grade 3-4 AEs, AEs related to study drug, grade 3-4 AEs related to study drug.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Must understand and voluntarily sign an informed consent form.

2. Must be greater than or equal to 18 years at the time of signing the informed consent form.

3. Must be able to adhere to the study visit schedule and other protocol requirements.

4. Must have a documented diagnosis of B-cell CLL (IWCLL guidelines for the diagnosis and treatment of chronic lymphocytic leukemia [Hallek, 2008]).

5. Must have been treated with one of the following in first and/or second line:

• a purine analog-containing regimen

• a bendamustine-containing regimen

• an anti-CD20 antibody-containing regimen

• a chlorambucil-containing regimen

• an alemtuzumab-containing regimen (for those subjects with a 17p deletion)

1. Must have achieved a minimum response of partial response (PR, nPR, CRi, CR, and MRD-negative CR) (IWCLL guidelines for the diagnosis and treatment of chronic lymphocytic leukemia [Hallek, 2008]) following completion of second-line induction therapy prior to randomization (documentation of response status must be available). Second-line induction therapy must be documented to have been of sufficient duration.

2. Must have completed last cycle of second-line induction no less than 8 weeks (56 days) and no greater than 20 weeks (140 days) prior to randomization.

3. Must have an ECOG performance status score of less than or equal to 2.

4. Females of childbearing potential (FCBP)† must:

• Have two negative medically supervised pregnancy tests prior to starting of study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices complete and continued sexual abstinence.

• Either commit to continued abstinence from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.

1. Male subjects must:

• Commit to continued abstinence from heterosexual contact or agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after cessation of study therapy.

• Agree to not donate semen during study drug therapy and for a period after end of study drug therapy.

1. All subjects must:

• Have an understanding that the study drug could have a potential teratogenic risk.

• Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy. • Agree not to share study medication with another person.

• All subjects must be counseled about pregnancy precautions and risks of fetal exposure.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

2. Active infections requiring systemic antibiotics.

3. Systemic infection that has not resolved > 2 months prior to initiating lenalidomide treatment in spite of adequate anti-infective therapy

4. Autologous or allogeneic bone marrow transplant as second-line therapy.

5. Pregnant or lactating females.

6. Systemic treatment for B-cell CLL in the interval between completing the last cycle of second-line induction therapy and randomization.

7. Participation in any clinical study or having taken any investigational therapy for a disease other than CLL within 28 days prior to initiating maintenance therapy.

8. Known presence of alcohol and/or drug abuse.

9. Central nervous system involvement as documented by spinal fluid cytology or imaging. Subjects who have signs or symptoms suggestive of leukemic meningitis or a history of leukemic meningitis must have a lumbar puncture procedure performed within two weeks prior to randomization.

10. Prior history of malignancies, other than CLL, unless the subject has been free of the disease for ≥5 years. Exceptions include the following:

• Basal cell carcinoma of the skin

• Squamous cell carcinoma of the skin

• Carcinoma in situ of the cervix

• Carcinoma in situ of the breast

• Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)

1. History of renal failure requiring dialysis.

2. Known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), and/or active Hepatitis C Virus (HCV) infection.

3. Prior therapy with lenalidomide.

4. Evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be enrolled upon correction of electrolyte abnormalities).

5. Any of the following laboratory abnormalities:

• Calculated (method of Cockroft-Gault) creatinine clearance <60 mL/min.

• Absolute neutrophil count (ANC) <1,000/μL (1.0 X 109/L)

• Platelet count <50,000/μL (50 X 109/L)

• Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT)

3.0 x upper limit of normal (ULN)

• Serum total bilirubin >2.0 mg/dL (with the exception of Gilbert's Syndrome)

1. Grade 4 rash due to prior thalidomide treatment

2. Uncontrolled hyperthyroidism or hypothyroidism

3. Venous thromboembolism within one year

4. Greater than or equal to Grade-2 neuropathy

5. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia

6. Disease transformation (active) (ie, Richter's Syndrome, prolymphocytic leukemia)

7. Known allergy to allopurinol for subjects assessed with PR following their second-line induction therapy.

8. Prisoners.

9. More than 2 prior lines of CLL therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic - Arizona	Phoenix	Arizona	United States	85054
2	Pacific Coast Hematology Oncology	Fountain Valley	California	United States	92708
3	Kaiser Permanente Medical Group	San Diego	California	United States	92120
4	Sharp Memorial Hospital	San Diego	California	United States	92123
5	Stanford University Stanford	Stanford	California	United States	94305
6	University of Colorado Hospital	Aurora	Colorado	United States	80045
7	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218-1210
8	Cancer Center of Central Connecticut	Plainville	Connecticut	United States	06062
9	Boca Raton Community Hospital	Boca Raton	Florida	United States	33486
10	Pasco Hernando Oncology Associates, PA	Brooksville	Florida	United States	34613
11	Memorial Hospital	Hollywood	Florida	United States	33021
12	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
13	Florida Cancer Specialist	Tavares	Florida	United States	32778
14	Florida Hospital Cancer Institute Waterman	Tavares	Florida	United States	32778
15	Augusta Oncology Associates, P.C.	Augusta	Georgia	United States	30901
16	Northwest Georgia Oncology Centers, PCWilliam S. Gibbons Center Research Institute	Marietta	Georgia	United States	30060
17	Northwestern University, Division of Hematology Oncology, Dept. of Medicine	Chicago	Illinois	United States	60611
18	Rush University Medical Center	Chicago	Illinois	United States	60612
19	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426-3558
20	Edward Hines Jr VA Hospital	Hines	Illinois	United States	60141
21	North Chicago VA Medical Center	North Chicago	Illinois	United States	60064
22	Hematology Oncology Assoc. of IL Orchard Research LLC	Skokie	Illinois	United States	60076
23	Floyd Memorial Cancer Center of Indiana, a division of Floyd Memorial Hospital and Health Services	New Albany	Indiana	United States	47150
24	McFarland Clinic	Ames	Iowa	United States	50010
25	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101-1733
26	Ochsner Medical Institutions	New Orleans	Louisiana	United States	70121
27	Clinical Unit for Research Trials in Skin CURTIS Massachusetts General Hospital	Boston	Massachusetts	United States	02114
28	Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
29	The Cancer Center, Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
30	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
31	Winthrop University Hospital	Mineola	New York	United States	11501
32	Biomedical Research Alliance of New York, LLC	New Hyde Park	New York	United States	11042
33	SUNY Upstate Medical University Medicine Oncology	Syracuse	New York	United States	13215
34	Westchester County Medical Center	Valhalla	New York	United States	10595
35	Wake Forest Univ. Health Sciences Outpatient Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157
36	Gabrail Cancer Center Research	Canton	Ohio	United States	44718
37	The Christ Hospital	Cincinnati	Ohio	United States	45219
38	Oncology Hematology Care	Cincinnati	Ohio	United States	45242
39	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
40	Cleveland Clinic	Cleveland	Ohio	United States	44195
41	Hematology Oncology Consultants, Inc.	Columbus	Ohio	United States	43235
42	Gabrail Cancer Center Research	Dover	Ohio	United States	44622
43	Trilogy Cancer Care	Wooster	Ohio	United States	44691
44	Kaiser Permanente Northwest Oncology Hematology	Portland	Oregon	United States	97227
45	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
46	Gettysburg Cancer Center	Gettysburg	Pennsylvania	United States	17325
47	Drexel University, College of Medicine, Clinical Research Group	Philadelphia	Pennsylvania	United States	19102
48	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224
49	Abington Hematology Oncology Associates Inc	Willow Grove	Pennsylvania	United States	19090
50	Charleston Hematology Oncology P.A.	Charleston	South Carolina	United States	29403
51	M. Francisco Gonzalez, MD, PA	Sumter	South Carolina	United States	29150
52	Sarah Cannon Cancer Center	Nashville	Tennessee	United States	37203
53	UT Southwestern Medical Center	Dallas	Texas	United States	75390
54	Swedish Cancer Institute	Seattle	Washington	United States	98104
55	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
56	Gundersen Clinic Lutheran Hospital	La Crosse	Wisconsin	United States	54601
57	Concord Hospital	Concord	New South Wales	Australia	2139
58	Haematology and Oncology Clinics of Australasia	South Brisbane	Queensland	Australia	4101
59	IMVS	Adelaide	South Australia	Australia	5000 SA
60	Flinders Medical Centre	Bedford Park		Australia	5042
61	Royal Prince Alfred Hospital	Camperdown		Australia	2050
62	Peter MacCallum Cancer Centre	East Melbourne		Australia	3006
63	Frankston Hospital	Farkston		Australia	3199
64	St. Vincent Hospital	Fitzroy		Australia	3065
65	Nepean Hospital	Kingswood, NSW		Australia	2751
66	Clinical Trials Unit The St George Hospital	Kogarah		Australia	2217
67	Sir Charles Gairdner Hospital	Nedlands		Australia	6009
68	Royal North Shore HospitalDepartment of HematologyLevel 4	St. Leonards		Australia	2065
69	The Queen Elizabeth Hospital	Woodville		Australia	5011
70	Universitaetsklinik Innsbruck	Innsbruck		Austria	6020
71	Hospital Bamherzige Schwestern	Linz		Austria	4010
72	Medical University of Vienna Internalmedicine 1, Hematology	Vienna		Austria	1190
73	AZ Sint-Jan AV Brugge	Brugge		Belgium	8000
74	Institut Jules Bordet	Brussels		Belgium	1000
75	Cliniques Universitaires St Luc	Bruxelles		Belgium	1200
76	UZ Gent Hematology	Gent		Belgium	9000
77	Hopital de Jolimont	Haine-Saint Paul		Belgium	7100
78	AZ Groeninge	Kortrijk		Belgium	8500
79	UZ Leuven	Leuven		Belgium	3000
80	CHU Mont -Godinne	Yvoir		Belgium	5530
81	Regional Health Authority B-Saint John Regional Hospital	Saint John	New Brunswick	Canada	E2L 4L2
82	General Hospital, Eastern Health	St John's	Newfoundland and Labrador	Canada	A1B 3V6
83	CDHA Centre for Clinical Research	Halifax	Nova Scotia	Canada	B3H 1V7
84	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
85	CIUSSS de l'Est-de-l'Ile-de-Montreal	Montreal/Quebec	Quebec	Canada
86	McGill University	Montreal	Quebec	Canada	H2W 1S6
87	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec	Canada	H4J 1C5
88	Hopital De L'Enfant-Jesus	Quebec		Canada	G1J 1Z4
89	Oncomedica S.A.	Monteria		Colombia
90	Interni hematoonkologicka klinika	Brno		Czechia	625 00
91	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czechia	500 05
92	Poliklinika Agel Novy Jicin	Novy Jicin		Czechia	74101
93	Faculty Hospital Plzen	Plzen		Czechia	30460
94	Faculty Hospital Kralovske Vinohrady	Prague		Czechia	100 00
95	General Faculty Hosital1.Internal Clinic	Prague		Czechia	12808
96	Rigshospitalet University Hospital	Copenhagen		Denmark	2100
97	Odense University Hospital	Odense		Denmark	DK-5000
98	Vejle Hospital	Vejle		Denmark	7100
99	Hopital Aviecenne	Bobigny Cedex		France	93009
100	Bergonie Institut	Bordeaux		France	33076
101	CMRU-Hotel Dieu Service Hematologie Clinique et Therapie Cellulaire	Clermont Ferrand		France	63000
102	CHU Hopital Michallon	Grenoble Cedex 09		France	38043
103	Centre Hospitalier Lyon Sud	Lyon		France	69495
104	Cetre Hospitalier Hotel-Dieu	Nantes cedex 01		France	44093
105	Hopital de l'Archet 1	Nice		France	06200
106	Hopital Petie- SalpetriereDepartment d'Hematologie	Paris		France	Cedex 13
107	CHU La Miletrie	Poitiers		France	86021
108	CHU de Reims	Reims cedex		France	51092
109	CLCC H BecquerelHematology	Rouen		France	76038
110	Hopital Bretonneau	Tours Cedex		France	37044
111	Charite, Campus Benjamin Franklin, Medizinische Klinik III	Berlin		Germany	12203
112	Universitaetsklinikum EssenZentrum fuer Innere Medizin	Essen		Germany	45122
113	Innere Medizin Klinikum Frankfurt Oder GmBH	Frankfurt (Oder)		Germany	15236
114	Universitaetsklinikum FreiburgInnere Med.1, Haematologie	Freiburg		Germany	79106
115	Medizinische Hochschule Hannover	Hannover		Germany	30625
116	Praxis fuer Haematologie und Onkologie Koblenz	Koblenz		Germany	56068
117	Klinikum der Universitat zu Koln	Köln		Germany	50937
118	Universitatsklinikum Leipzig	Leipzig		Germany	04103
119	Mannheimer Onkologie Praxis	Mannheim		Germany	68161
120	Stadtisches Klinikum Munchen GmbH	München		Germany	80804
121	TU München - Klinikum rechts der Isar	München		Germany	81675
122	Facharzte fur Innere Medizin Hämatologie und Onkologie Gemeinschaftspraxis	Münster		Germany	48149
123	University Hospital of Ulm	Ulm		Germany	89081
124	Semmelweis Egyetem	Budapest		Hungary	1083
125	Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum	Debrecen		Hungary	4032
126	Petz Aladar Country Hospital	Gyor		Hungary	9024
127	Kaposi Mor Oktato Korhaz	Kaposvar		Hungary	7400
128	Pecsi Tudomanyegytem Altalanos Orvostudomanyi Kar	Pecs		Hungary	7624
129	Szegedi TudomanyegyetemII Belgyogyaszati Klinika	Szeged		Hungary	6720
130	Komarom-Esztergom Megye Onkormanyzat Szent Borbala Korhaza	Tatabanya		Hungary
131	St James's Hospital	Dublin		Ireland	8
132	Midwestern Regional Hospital	Limerick		Ireland
133	Ha'Emek Medical Center	Afula		Israel	18101
134	Barzilai Medical Center	Ashkelon		Israel	78278
135	Soroka University Medical Center	Beer Sheva		Israel	84101
136	Bnei Zion Medical Center	Haifa		Israel	31048
137	Rambam Health Care Campus	Haifa		Israel	31096
138	Shaare Zedek Medical Center	Jerusalem		Israel	91031
139	Meir Medical Center	Kfar-Saba		Israel	44281
140	Western Galilee Hospital	Naharia		Israel	22100
141	Rabin Medical Center	Petach Tikva		Israel	49100
142	Kaplan Medical Center	Rehovot		Israel	76100
143	Tel Aviv Sourasky Medical Center Department of Hematology	Tel Aviv		Israel	64239
144	Sheba Medical Center	Tel Hashomer		Israel	52621
145	Azienda Ospedaliera Poloclinico di Bari	Bari		Italy	70124
146	Istituto dei Tumori Giovanni Paolo II di Bari	Bari		Italy	70124
147	AO Spedali Civili di Brescia	Brescia		Italy	25123
148	Azienda Ospedaliera Vittorio Emanuele-Ferrarotto	Catania		Italy	95124
149	A.O. Pugliese Ciaccio	Catanzaro		Italy	88100
150	Azienda Ospedaliera Annunziala	Cosenza		Italy	87100
151	Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi	Ferrara		Italy	44100
152	Azienda Ospedaliera Universitaria Careggi	Florence		Italy	50139
153	Azienda Ospedaliero Universitaria OORR Foggia	Foggia		Italy	71100
154	Azienda Ospedaliera San Martino	Genova		Italy	16132
155	Fondazione Centro San Raffaele del Monte Tabor	Milano		Italy	20132
156	Istituto Oncologico Europeo	Milano		Italy	20141
157	IRCSS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena	Milan		Italy	20122
158	Azienda Ospedaliero Universitaria di Modena	Modena		Italy	41100
159	Ospedale Cardarelli	Naples		Italy	80131
160	Policlinico Universitario Federico II	Naples		Italy	80131
161	Universita del Piemonte Orientale	Novara		Italy	28100
162	Universita degli Studi di Padova	Padova		Italy	35128
163	Azienda Ospedaliera Ospedale San Carlo	Potenza		Italy	85100
164	Ospedale Sant'Eugenio	Rome		Italy	00144
165	Azienda Policlinico Umberto I, Universita La Sapienzadi Roma	Rome		Italy	00161
166	Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte	Siena		Italy	53100
167	Osp. S.Giovanni Battista Le Molinette	Torino		Italy	10126
168	Ospedale Umberto I	Torrette Di Ancona		Italy	60020
169	Ospedale San Bortolo di Vicenza	Vicenza		Italy	36100
170	Instituto Biomedico de Investigacion AC	Aguascalientes		Mexico	20127
171	VU University Medical Center	Amsterdam		Netherlands	1081 HV
172	Christchurch Hospital	Christchurch		New Zealand
173	Middlemore Clinical Trials	Manukau		New Zealand	1640
174	North Shore Hospital	Takapuna		New Zealand	1309
175	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-952
176	Malopolskie Centrum Medyczne S.C.	Kraków		Poland	30-510
177	Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi	Lodz		Poland	93-510
178	Specjalistyczny Szpital miejski im. Kopernika	Torun		Poland	87-100
179	Centralny Szpital Kliniczny MON	Warszawa		Poland	04-141
180	Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu	Wroclaw		Poland	50-367
181	Hospitais da Universidade de Coimbra	Coimbra		Portugal	3000 - 075
182	Hospital de Dia de Hematologia	Lisbon		Portugal	1649-035
183	Instituto Portugues Oncologia do Porto Francisco Gentil EPE	Porto		Portugal	4200-072
184	Institutul Clinic Fundeni	Bucharest		Romania	022328
185	Spitalul Clinic Coltea	Bucharest		Romania	030171
186	Spitalul Clinic Judetean de Urgenta Sf Spiridon Iasi	Iasi		Romania	700111
187	Spitalul Clinic Judetean de Urgenta Sibiu	Sibiu		Romania	550245
188	Spitalul Clinic Municipal de Urgenta Timisoara	Timisoara		Romania	300079
189	Archangelsk Regional Clinical Hospital	Arkhangelsk		Russian Federation	163045
190	City Hospital 8	Barnaul		Russian Federation	659010
191	State Healthcare Institution Sverdlovsk regional clinical hospital 1	Ekaterinburg		Russian Federation	620102
192	GMU Republic clinical hospital	Kazan		Russian Federation	420012
193	Krasnoyarsk Regional Clinical Hospital	Krasnoyarsk		Russian Federation	660022
194	Institution of Russian Academy of Medical Sciences Russian Oncological Research Centre n.a. N. N. Bl	Moscow		Russian Federation	115447
195	State Budgetary Institution of the City of Moscow	Moscow		Russian Federation	123182
196	NUZ Central Clinical Hospital	Moscow		Russian Federation	129128
197	Nizhegorodskaya Regional Clinical Hospital n.a. N.A. Semashko	Nizhniy Novgorod		Russian Federation	603126
198	MUZ City Clinical Hospital 2	Novosibirsk		Russian Federation	630051
199	Federal State Budgetary Establishment Medical Radiological Research Center Ministry of Health and so	Obninsk		Russian Federation	249036
200	Saratov State Medical University	Saratov		Russian Federation	410012
201	FGU Russian Scientific Research Institute of Haematology and Transfusiology of Federal Agency	St. Petersburg		Russian Federation	191024
202	GUS Leningrad Regional Clinical Hospital	St. Petersburg		Russian Federation	194291
203	Federal State Institution Federal Centre of Heart, Blood and Endocrinology of Rosmedtechnologies	St. Petersburg		Russian Federation	197341
204	St. Petersburg Pavlov State Medical Univ	St.Petersburg		Russian Federation	197022
205	GUZ Volgograd Regional Clinical Oncology	Volgograd		Russian Federation	400138
206	Groote Schuur Hospital	Cape Town		South Africa
207	University Witwatersrand Oncology	Parktown		South Africa	2193
208	Pretoria Academic Hospital	Pretoria		South Africa	0002
209	Mary Potter Oncology Centre	Pretoria		South Africa
210	Wilgers Oncology CentreWilgrers Hospital	Pretoria		South Africa
211	Hospital Germans Trias I Pujol	Badalona		Spain	08916
212	Hospital del Mar	Barcelona		Spain	08003
213	Hospital Universitario Vall D hebron	Barcelona		Spain	08035
214	Hospital Universitario de la Princesa	Madrid		Spain	28006
215	Hospital Ramon y Cajal	Madrid		Spain	28034
216	Hospital 12 de Octubre	Madrid		Spain	28041
217	Hospital La Paz	Madrid		Spain	28046
218	Hospital Universitario Puerta de Hierro-Majadahonda	Majadahonda		Spain	28222
219	Virgen de la Victoria Hospital Malaga	Malaga		Spain	29010
220	Hospital General Universitario Morales Messeguer	Murcia		Spain	30008
221	Hospital Universitario de Salamanca	Salamanca		Spain	37007
222	Hospital Donostia	San Sebastian		Spain	20014
223	Hospital Universitario Marques de Valdecilla	Santander		Spain	39008
224	Hospital Clinico Universitario	Valencia		Spain	46010
225	Skane University Hospital	Lund		Sweden	221 85
226	Stockholm South Hospital	Stockholm		Sweden	11883
227	Karolinska University	Stockholm		Sweden	14186
228	Royal Bournemouth General Hospital	Bournemouth		United Kingdom	BH7 7DW
229	Addenbrookes Hospital	Cambridge		United Kingdom	CB2 0QQ
230	Gartnavel General Hospital	Glasgow		United Kingdom	G12 0YN
231	John Radcliffe Hospital	Headington		United Kingdom	OX3 9DU
232	Saint James University Hospital	Leeds		United Kingdom	LS9 7TF
233	Royal Liverpool University Hospital	Liverpool		United Kingdom	L78XP
234	St. Bartholomew's and The Royal London Hospital	London		United Kingdom	EC1A 7BE
235	Guy's and St. Thomas' Hospital	London		United Kingdom	SE1 9RT
236	King's College Hospital	London		United Kingdom	SE5 9RS
237	St George's Healthcare NHS Trust	London		United Kingdom	SW17 0QT
238	Christie Hospital NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
239	Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Trust	Sheffield		United Kingdom	S10 2JF
240	Singleton Hospital, Southwest Wales Cancer Inst	Swansea		United Kingdom	SA28QA
241	Sandwell Hospital	West Bromwich		United Kingdom	B71 4HJ

Sponsors and Collaborators

• Celgene

Investigators

• Study Director: Richard Delarue, MD, Celgene Corporation

Study Documents (Full-Text)

• Study Protocol - Mar 16, 2018
• Statistical Analysis Plan - Oct 16, 2015

More Information

Publications

None provided.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT00774345
• Other Study ID Numbers: CC-5013-CLL-002
• First Posted: Oct 17, 2008
• Last Update Posted: Dec 2, 2021
• Last Verified: Nov 1, 2021

• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lenalidomide

Study Results

Participant Flow

Pre-assignment Detail	317 randomized and 315 treated.

Arm/Group Title	Lenalidomide	Placebo
Arm/Group Description	2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR	2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR
Period Title: Pre-treatment
STARTED	160	157
COMPLETED	158	157
NOT COMPLETED	2	0
Period Title: Pre-treatment
STARTED	158	157
Participants Escalated to 5mg	129	149
Participants Escalated to 10mg	68	88
COMPLETED	0	0
NOT COMPLETED	158	157

Baseline Characteristics

Arm/Group Title	Lenalidomide	Placebo	Total
Arm/Group Description	2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR	2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR	Total of all reporting groups
Overall Participants	160	157	317
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.9 (8.08)	62.5 (8.85)	62.7 (8.46)
Sex: Female, Male (Count of Participants)
Female	45 28.1%	44 28%	89 28.1%
Male	115 71.9%	113 72%	228 71.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 3.8%	1 0.6%	7 2.2%
Not Hispanic or Latino	153 95.6%	156 99.4%	309 97.5%
Unknown or Not Reported	1 0.6%	0 0%	1 0.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 1.9%	2 1.3%	5 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.6%	1 0.3%
Black or African American	1 0.6%	4 2.5%	5 1.6%
White	154 96.3%	150 95.5%	304 95.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 1.3%	0 0%	2 0.6%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) is defined as the time from randomization to death from any cause. OS will be censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
Time Frame	Up to approximately 11 years

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Lenalidomide	Placebo
Arm/Group Description	2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR	2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR
Measure Participants	160	157
Median (95% Confidence Interval) [Months]	95.09	73.28

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.276
	Comments	The p-value is based on a stratified log-rank test.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the stratified cox proportional hazards model comparing the hazard functions associated with the treatment groups.

2. Secondary Outcome

Title	Progression Free Survival 2 (PFS2)
Description	Progression Free Survival (PFS2) assessed by investigator is defined as the time from randomization to the second objective disease progression, or death from any cause, whichever occurs first.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

All randomized evaluable participants

Arm/Group Title	Lenalidomide	Placebo
Arm/Group Description	2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR	2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR
Measure Participants	160	154
Median (95% Confidence Interval) [Months]	NA	35.9

3. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	Number of participants with adverse events (AEs) that measure type, frequency and severity of AEs graded by National Cancer Institute Common Terminology Criteria (NCI CTCAE V 3.0) including any grade adverse events (AEs), Grade 3-4 AEs, AEs related to study drug, grade 3-4 AEs related to study drug.
Time Frame	From first dose to 30 days post last dose (up to 9 years)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Lenalidomide	Placebo
Arm/Group Description	2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR	2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR
Measure Participants	158	157
Adverse Events (AEs)	155 96.9%	149 94.9%
Grade 3-4 AEs	136 85%	73 46.5%
AEs related to Study drugs	143 89.4%	98 62.4%
Grade 3-4 AEs related to Study drugs	117 73.1%	41 26.1%

Adverse Events

Time Frame	Up to 9 years
Arm/Group Title	Lenalidomide		Placebo
Arm/Group Description	2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR		2.5mg QD PO with escalation after 28 days to 5mg QD PO x 28 days, only if the 2.5mg dose was tolerated. Participants could be escalated to 10mg QD PO x 28 days, but only after 5 continuous cycles at 5mg and only if 5mg was well tolerated and if those participants had not achieved MRD-negative CR
All Cause Mortality
	Lenalidomide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/158 (49.4%)		80/157 (51%)
Serious Adverse Events
	Lenalidomide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/158 (62.7%)		49/157 (31.2%)
Blood and lymphatic system disorders
Anaemia	1/158 (0.6%)		0/157 (0%)
Anaemia haemolytic autoimmune	3/158 (1.9%)		2/157 (1.3%)
Autoimmune pancytopenia	1/158 (0.6%)		0/157 (0%)
Febrile neutropenia	3/158 (1.9%)		0/157 (0%)
Haemolytic anaemia	1/158 (0.6%)		0/157 (0%)
Leukopenia	1/158 (0.6%)		0/157 (0%)
Lymphopenia	2/158 (1.3%)		1/157 (0.6%)
Neutropenia	49/158 (31%)		13/157 (8.3%)
Thrombocytopenia	7/158 (4.4%)		0/157 (0%)
Cardiac disorders
Acute myocardial infarction	1/158 (0.6%)		0/157 (0%)
Angina pectoris	1/158 (0.6%)		1/157 (0.6%)
Atrial fibrillation	1/158 (0.6%)		2/157 (1.3%)
Atrioventricular block first degree	0/158 (0%)		1/157 (0.6%)
Cardiac failure congestive	1/158 (0.6%)		0/157 (0%)
Myocardial ischaemia	1/158 (0.6%)		0/157 (0%)
Sick sinus syndrome	1/158 (0.6%)		0/157 (0%)
Eye disorders
Eye movement disorder	1/158 (0.6%)		0/157 (0%)
Optic neuropathy	1/158 (0.6%)		0/157 (0%)
Gastrointestinal disorders
Abdominal pain	1/158 (0.6%)		1/157 (0.6%)
Abdominal pain upper	0/158 (0%)		1/157 (0.6%)
Diarrhoea	3/158 (1.9%)		1/157 (0.6%)
Gastrointestinal haemorrhage	1/158 (0.6%)		0/157 (0%)
Inguinal hernia	0/158 (0%)		1/157 (0.6%)
Umbilical hernia	0/158 (0%)		1/157 (0.6%)
General disorders
Fatigue	1/158 (0.6%)		0/157 (0%)
Impaired healing	1/158 (0.6%)		0/157 (0%)
Pyrexia	3/158 (1.9%)		3/157 (1.9%)
Soft tissue inflammation	0/158 (0%)		1/157 (0.6%)
Hepatobiliary disorders
Biliary colic	1/158 (0.6%)		0/157 (0%)
Cholelithiasis	2/158 (1.3%)		0/157 (0%)
Hepatitis toxic	1/158 (0.6%)		0/157 (0%)
Hyperbilirubinaemia	0/158 (0%)		1/157 (0.6%)
Infections and infestations
Appendicitis	0/158 (0%)		1/157 (0.6%)
Arthritis bacterial	1/158 (0.6%)		0/157 (0%)
Bacteraemia	1/158 (0.6%)		0/157 (0%)
Bacterial sepsis	1/158 (0.6%)		0/157 (0%)
Bone tuberculosis	1/158 (0.6%)		0/157 (0%)
Bronchitis	0/158 (0%)		1/157 (0.6%)
Bronchopneumonia	1/158 (0.6%)		0/157 (0%)
Cellulitis	2/158 (1.3%)		0/157 (0%)
Disseminated tuberculosis	1/158 (0.6%)		0/157 (0%)
Empyema	1/158 (0.6%)		0/157 (0%)
Epstein-Barr viraemia	1/158 (0.6%)		0/157 (0%)
Gastroenteritis	1/158 (0.6%)		1/157 (0.6%)
Gastroenteritis norovirus	1/158 (0.6%)		0/157 (0%)
Gastroenteritis viral	2/158 (1.3%)		0/157 (0%)
H1N1 influenza	1/158 (0.6%)		0/157 (0%)
Hepatitis B	1/158 (0.6%)		0/157 (0%)
Herpes virus infection	0/158 (0%)		1/157 (0.6%)
Herpes zoster ophthalmic	0/158 (0%)		1/157 (0.6%)
Influenza	1/158 (0.6%)		0/157 (0%)
Lobar pneumonia	2/158 (1.3%)		1/157 (0.6%)
Lower respiratory tract infection	3/158 (1.9%)		1/157 (0.6%)
Lymph node abscess	0/158 (0%)		1/157 (0.6%)
Neutropenic sepsis	2/158 (1.3%)		0/157 (0%)
Orchitis	0/158 (0%)		1/157 (0.6%)
Otitis media	0/158 (0%)		1/157 (0.6%)
Parainfluenzae virus infection	1/158 (0.6%)		0/157 (0%)
Pharyngitis	2/158 (1.3%)		0/157 (0%)
Pneumocystis jiroveci pneumonia	1/158 (0.6%)		1/157 (0.6%)
Pneumonia	7/158 (4.4%)		8/157 (5.1%)
Pneumonia escherichia	1/158 (0.6%)		0/157 (0%)
Pneumonia mycoplasmal	1/158 (0.6%)		0/157 (0%)
Pneumonia pneumococcal	1/158 (0.6%)		0/157 (0%)
Pneumonia primary atypical	1/158 (0.6%)		0/157 (0%)
Post procedural infection	0/158 (0%)		1/157 (0.6%)
Pulmonary sepsis	0/158 (0%)		1/157 (0.6%)
Pyelonephritis	2/158 (1.3%)		0/157 (0%)
Respiratory tract infection	3/158 (1.9%)		0/157 (0%)
Respiratory tract infection viral	1/158 (0.6%)		0/157 (0%)
Salmonella sepsis	1/158 (0.6%)		0/157 (0%)
Sepsis	5/158 (3.2%)		0/157 (0%)
Septic shock	1/158 (0.6%)		0/157 (0%)
Sinusitis	0/158 (0%)		1/157 (0.6%)
Sinusitis bacterial	0/158 (0%)		1/157 (0.6%)
Urinary tract infection	1/158 (0.6%)		0/157 (0%)
Urinary tract infection bacterial	1/158 (0.6%)		0/157 (0%)
Viral labyrinthitis	0/158 (0%)		1/157 (0.6%)
Viral pericarditis	1/158 (0.6%)		0/157 (0%)
Injury, poisoning and procedural complications
Cervical vertebral fracture	1/158 (0.6%)		0/157 (0%)
Contusion	0/158 (0%)		1/157 (0.6%)
Road traffic accident	0/158 (0%)		2/157 (1.3%)
Investigations
Blood bicarbonate decreased	1/158 (0.6%)		0/157 (0%)
International normalised ratio increased	1/158 (0.6%)		0/157 (0%)
Metabolism and nutrition disorders
Dehydration	0/158 (0%)		1/157 (0.6%)
Hypercalcaemia	0/158 (0%)		1/157 (0.6%)
Hyperglycaemia	1/158 (0.6%)		0/157 (0%)
Hyponatraemia	1/158 (0.6%)		0/157 (0%)
Type 2 diabetes mellitus	1/158 (0.6%)		0/157 (0%)
Musculoskeletal and connective tissue disorders
Haemarthrosis	1/158 (0.6%)		0/157 (0%)
Mobility decreased	1/158 (0.6%)		0/157 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/158 (0.6%)		0/157 (0%)
Basal cell carcinoma	9/158 (5.7%)		8/157 (5.1%)
Bladder cancer	1/158 (0.6%)		0/157 (0%)
Bowen's disease	1/158 (0.6%)		0/157 (0%)
Colon cancer	1/158 (0.6%)		1/157 (0.6%)
Colon cancer stage III	1/158 (0.6%)		0/157 (0%)
Hodgkin's disease	1/158 (0.6%)		0/157 (0%)
Keratoacanthoma	0/158 (0%)		1/157 (0.6%)
Lung neoplasm malignant	1/158 (0.6%)		0/157 (0%)
Malignant melanoma	1/158 (0.6%)		1/157 (0.6%)
Meningioma	0/158 (0%)		1/157 (0.6%)
Metastases to liver	1/158 (0.6%)		0/157 (0%)
Prostate cancer	0/158 (0%)		2/157 (1.3%)
Rectal cancer	0/158 (0%)		1/157 (0.6%)
Rectosigmoid cancer	1/158 (0.6%)		0/157 (0%)
Small intestine carcinoma	1/158 (0.6%)		0/157 (0%)
Squamous cell carcinoma of skin	8/158 (5.1%)		4/157 (2.5%)
Thyroid cancer	1/158 (0.6%)		0/157 (0%)
Tumour flare	1/158 (0.6%)		0/157 (0%)
Nervous system disorders
Cerebral infarction	1/158 (0.6%)		0/157 (0%)
Cranial nerve disorder	0/158 (0%)		1/157 (0.6%)
Demyelination	1/158 (0.6%)		0/157 (0%)
Diplegia	0/158 (0%)		1/157 (0.6%)
Migraine	0/158 (0%)		1/157 (0.6%)
Peripheral sensory neuropathy	1/158 (0.6%)		0/157 (0%)
Syncope	1/158 (0.6%)		1/157 (0.6%)
Transient ischaemic attack	1/158 (0.6%)		0/157 (0%)
Visual field defect	1/158 (0.6%)		0/157 (0%)
Renal and urinary disorders
Calculus urinary	1/158 (0.6%)		0/157 (0%)
Renal colic	0/158 (0%)		2/157 (1.3%)
Renal failure	1/158 (0.6%)		0/157 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/158 (0%)		1/157 (0.6%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/158 (0.6%)		0/157 (0%)
Asthma	2/158 (1.3%)		1/157 (0.6%)
Bronchospasm	1/158 (0.6%)		0/157 (0%)
Chronic obstructive pulmonary disease	2/158 (1.3%)		1/157 (0.6%)
Hypoxia	1/158 (0.6%)		0/157 (0%)
Organising pneumonia	0/158 (0%)		1/157 (0.6%)
Pleural effusion	0/158 (0%)		1/157 (0.6%)
Pulmonary embolism	4/158 (2.5%)		1/157 (0.6%)
Pulmonary haemorrhage	1/158 (0.6%)		0/157 (0%)
Respiratory failure	1/158 (0.6%)		0/157 (0%)
Skin and subcutaneous tissue disorders
Dermatitis herpetiformis	1/158 (0.6%)		0/157 (0%)
Erythema multiforme	0/158 (0%)		1/157 (0.6%)
Toxic epidermal necrolysis	0/158 (0%)		1/157 (0.6%)
Vascular disorders
Circulatory collapse	1/158 (0.6%)		0/157 (0%)
Hypotension	1/158 (0.6%)		0/157 (0%)
Other (Not Including Serious) Adverse Events
	Lenalidomide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	152/158 (96.2%)		140/157 (89.2%)
Blood and lymphatic system disorders
Anaemia	9/158 (5.7%)		7/157 (4.5%)
Leukopenia	12/158 (7.6%)		2/157 (1.3%)
Neutropenia	106/158 (67.1%)		44/157 (28%)
Thrombocytopenia	44/158 (27.8%)		19/157 (12.1%)
Gastrointestinal disorders
Abdominal pain	18/158 (11.4%)		9/157 (5.7%)
Abdominal pain upper	9/158 (5.7%)		4/157 (2.5%)
Constipation	27/158 (17.1%)		8/157 (5.1%)
Diarrhoea	65/158 (41.1%)		26/157 (16.6%)
Dyspepsia	12/158 (7.6%)		8/157 (5.1%)
Nausea	26/158 (16.5%)		27/157 (17.2%)
Vomiting	12/158 (7.6%)		13/157 (8.3%)
General disorders
Asthenia	10/158 (6.3%)		2/157 (1.3%)
Chills	10/158 (6.3%)		1/157 (0.6%)
Fatigue	56/158 (35.4%)		54/157 (34.4%)
Influenza like illness	11/158 (7%)		2/157 (1.3%)
Oedema peripheral	16/158 (10.1%)		12/157 (7.6%)
Pyrexia	28/158 (17.7%)		17/157 (10.8%)
Infections and infestations
Bronchitis	22/158 (13.9%)		12/157 (7.6%)
Herpes zoster	9/158 (5.7%)		9/157 (5.7%)
Influenza	14/158 (8.9%)		3/157 (1.9%)
Lower respiratory tract infection	12/158 (7.6%)		7/157 (4.5%)
Nasopharyngitis	16/158 (10.1%)		18/157 (11.5%)
Oral herpes	10/158 (6.3%)		7/157 (4.5%)
Pharyngitis	10/158 (6.3%)		7/157 (4.5%)
Pneumonia	10/158 (6.3%)		2/157 (1.3%)
Respiratory tract infection	14/158 (8.9%)		10/157 (6.4%)
Sinusitis	16/158 (10.1%)		5/157 (3.2%)
Upper respiratory tract infection	31/158 (19.6%)		28/157 (17.8%)
Viral infection	8/158 (5.1%)		5/157 (3.2%)
Investigations
Blood bilirubin increased	8/158 (5.1%)		4/157 (2.5%)
Weight decreased	22/158 (13.9%)		14/157 (8.9%)
Weight increased	5/158 (3.2%)		9/157 (5.7%)
Metabolism and nutrition disorders
Decreased appetite	15/158 (9.5%)		9/157 (5.7%)
Hypokalaemia	10/158 (6.3%)		3/157 (1.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	23/158 (14.6%)		10/157 (6.4%)
Back pain	18/158 (11.4%)		20/157 (12.7%)
Muscle spasms	22/158 (13.9%)		10/157 (6.4%)
Musculoskeletal pain	11/158 (7%)		7/157 (4.5%)
Myalgia	4/158 (2.5%)		8/157 (5.1%)
Pain in extremity	13/158 (8.2%)		6/157 (3.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour flare	12/158 (7.6%)		9/157 (5.7%)
Nervous system disorders
Dizziness	16/158 (10.1%)		9/157 (5.7%)
Headache	17/158 (10.8%)		14/157 (8.9%)
Psychiatric disorders
Insomnia	10/158 (6.3%)		10/157 (6.4%)
Respiratory, thoracic and mediastinal disorders
Cough	46/158 (29.1%)		32/157 (20.4%)
Dyspnoea	16/158 (10.1%)		11/157 (7%)
Oropharyngeal pain	15/158 (9.5%)		16/157 (10.2%)
Productive cough	4/158 (2.5%)		10/157 (6.4%)
Rhinorrhoea	10/158 (6.3%)		4/157 (2.5%)
Skin and subcutaneous tissue disorders
Actinic keratosis	10/158 (6.3%)		3/157 (1.9%)
Erythema	8/158 (5.1%)		2/157 (1.3%)
Hyperhidrosis	11/158 (7%)		5/157 (3.2%)
Night sweats	30/158 (19%)		31/157 (19.7%)
Pruritus	20/158 (12.7%)		9/157 (5.7%)
Rash	42/158 (26.6%)		13/157 (8.3%)
Vascular disorders
Hypertension	8/158 (5.1%)		12/157 (7.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.