A Multicenter, Single-Arm, Open-Label Expanded Access Program for Lenalidomide Plus Dexamethasone in Previously Treated Subjects With Multiple Myeloma

• Sponsor: Celgene Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00478777
• Collaborator: (none)
• Enrollment: 150
• Locations: 48
• Arm: 1
• Duration (Months): 29
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was a multicenter, open-label, single-arm phase 3B study of the combination lenalidomide plus pulse high-dose dexamethasone.

This study (CC-5013-MM-019) was set up and executed primarily as an expanded access program in Germany.

Screening procedures were to take place within 28 days prior to Cycle 1 Day 1 (baseline) with the exception of hematology assessments that were to be performed within 14 days prior to Cycle 1 Day 1. Randomization, blinding, and stratification were not applied in this open-label single-arm study.

Eligible subjects given open-label treatment and received treatment with lenalidomide plus high-dose dexamethasone in 28-day cycles.

Lenalidomide (hard capsules) was to be administered orally (PO) at a dose of 25 mg daily (QD) for the first 21 days of each 28-day cycle. According to the protocol, accrual of subjects to the study was to be terminated within 2 months of commercial availability of lenalidomide for this indication in Germany.

Upon discontinuation from study, minimal information was collected in order to identify when disease progressed.

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Multiple Myeloma	Drug: Lenalidomide; Drug: dexamethasone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Single-Arm, Open-Label Expanded Access Program for Lenalidomide Plus Dexamethasone in Previously Treated Subjects With Multiple Myeloma
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Nov 1, 2007
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: lenalidomide plus dexamethasone Lenalidomide administered orally, 25 mg daily (QD) for the first 21 days of each 28-day cycle. Pulse dexamethasone administered orally, 40 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle during Cycles 1 to 4 (approximately months 1-4). Beginning with Cycle 5 (approximately month 5), dexamethasone was to be reduced to 40 mg QD for Days 1-4 of each 28 day-cycle.

Drug: Lenalidomide; Oral lenalidomide at a dose of 25 mg daily for 21 days every 28 days. Treatment as tolerated until disease progression.; Other Names: Revlimid® ; Drug: dexamethasone; Oral pulse dexamethasone at a dose of 40 mg daily on days 1-4, 9-12, and 17-20 for each 28-day-cycle for cycles 1 through 4 (approximately months 1-4). Beginning cycle 5 (approximately month 5) dexamethasone is reduced to 40 mg daily for days 1-4 every 28 days.

Outcome Measures

Primary Outcome Measures

1. Kaplan Meier Estimate for Time to Disease Progression [up to 827 days]

   Time to disease progression (TTP) was based on the European Group for Blood and Marrow Transplantation (EBMT) myeloma response determination criteria developed by Bladé (Bladé, 1998). TTP is a Kaplan Meier estimate of the time from randomization to the first documentation of progressive disease. Progressive disease based on increasing monoclonal paraprotein levels require a confirmatory value one week apart. Disease progression can also be based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

Secondary Outcome Measures

1. Participant's Best Overall Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Criteria [Up to 827 days]

   Best overall response was calculated as the best assessment from all cycles (including treatment discontinuation visit) and follow-up. The response rate was summarized as complete response (CR), partial response (PR), stable disease (SD), progression (PD), response not evaluable, and derived categories (PR+CR) and (PR+CR+SD). CR is negative immunofixation on both serum and urine maintained for 6 weeks straight. PR is a 50% decrease in serum paraprotein maintained for 6 weeks straight. SD is serum paraprotein values within 25% of baseline.

2. Participants With Treatment-emergent Adverse Experiences (TEAEs) [up to 8 months]

   Counts of study participants who had treatment-emergent adverse events (TEAEs) defined as any reported AE that started on or after the first day of study drug dosing. A participant with multiple occurrences of an adverse event within a category is counted only once in that category. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) was used by investigators to assess TEAEs. Severity scale ranges from 0 (none) to 5 (death). Grade 3=severe AE; Grade 4=life threatening or disabling AE; Grade 5=death.

3. Time to Partial Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Determination Criteria [up to 827 days]

   Time to partial response is the time from randomization to a 50% decrease in serum paraprotein maintained for six weeks straight. This was determined by free light chain concentrations which were taken every two weeks during the treatment phase of the trial.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Must understand and voluntarily sign an informed consent form.

• Must be ≥18 years of age at the time of signing the informed consent form.

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

• Must be diagnosed with multiple myeloma that is progressing after at least 2 cycles of anti-myeloma treatment or that has relapsed with progressive disease after treatment.

• Subjects may have been previously treated with thalidomide and/or radiation therapy. In addition, radiation therapy initiated prior to or at baseline (Day 1) may be given concurrently with study therapy, provided that all other eligibility criteria are satisfied.

• Subjects must discontinue all anti-myeloma drug or non-drug therapy prior to the first dose of study drug with the exception of radiation therapy initiated prior to or at baseline (Day 1).

• Measurable levels of myeloma paraprotein in serum (>0.5 g/dL) or urine (>0.2 g excreted in a 24-hour collection sample).

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

• Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.

Exclusion Criteria:

• The presence of any of the following will exclude a subject from study enrollment:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

• Pregnant or lactating females.

• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

• Any of the following laboratory abnormalities:

• Absolute neutrophil count (ANC) <1,000 cells/mm^{3 (1.0 x 10}9/L)

• Platelet count <75,000/mm^3 (75 x 109/L) for subjects in whom <50% of the bone marrow nucleated cells are plasma cells.

• Platelet count <30,000/mm^{3 (30x10}9/L) for subjects in whom ≥50% of bone marrow nucleated cells are plasma cells.

• Serum creatinine >2.5 mg/dL (221 µmol/L)

• Serum SGOT/AST or SGPT/ALT >3.0 x upper limit of normal (ULN)

• Serum total bilirubin >2.0 mg/dL (34 µmol/L)

• Prior history of malignancies other than multiple myeloma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for ≥1 year.

• Prior history of stroke and/or thromboembolic event

• Known hypersensitivity to thalidomide or dexamethasone.

• Prior history of uncontrollable side effects to dexamethasone therapy.

• The development of a desquamating rash while taking thalidomide.

• Neuropathy ≥ Grade 2.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medizinische Klinik und Poliklinik II der Charité Universitätsmedizin Berlin Campus Mitte	Berlin		Germany	10117
2	Poliklinik I, Hämatologie/ Onkologie, Universitätsklinikum Bonn	Bonn		Germany	53105
3	Johanniter-Krankenhaus Bonn Friedrich-Wilhelm-Stift gGmbH	Bonn		Germany	53113
4	Medizinische Klinik Städtisches Klinikum Braunschweig gGmbH	Braunschweig		Germany	D-38114
5	Interne Klinik Dr. Argirov, Schön-Kliniken	Burg		Germany	82335
6	Klinik für Innere Medizin III Klinikum Chemnitz gGmbH	Chemnitz		Germany	09113
7	Medizinische Klinik und Poliklinik, Uniklinikum Dresden	Dresden		Germany	01307
8	Universitaetsklinikum Dusseldorf Klinik fuer Haematologie	Düsseldorf		Germany	40225
9	Direktor der Klinik f. Hämatologie, Universitätsklinikum Essen	Essen		Germany	45122
10	Universitätsklinikum EssenInnere Klinik und Poliklinik	Essen		Germany	45122
11	Klinik für Innere Medizin, Klinikum Frankfurt (Oder) GmbH	Frankfurt (Oder)		Germany	15236
12	Medizinische Klinik II (ZIM),Hämatologie / Onkologie Uniklinik Frankfurt	Frankfurt am Main		Germany	60590
13	Abt. Innere Medizin I , Hämatologie / Onkologie, Universitätsklinikum Freiburg	Freiburg		Germany	79106
14	Universitätsklinikum GöttingenHamatologie und Onkologie	Göttingen		Germany	37075
15	Interdisziplinäre Klinik und Poliklinik für Stammzellentransplantation Universitätsklinik Hamburg - Eppendorf	Hamburg		Germany	20246
16	II. Medizinische Abteilung, Asklepios Klinikum Altona	Hamburg		Germany	22763
17	Abt. Hämatologie, Hämatologie und Onkologie, Medizinische Hochschule Hannover	Hannover		Germany	30625
18	Medizinische Klinik und Poliklinik V Universitaetsklinikum Heidelberg	Heidelberg		Germany	69120
19	Klinik für Innere Medizin II Hämatologie / Onkologie Universitätsklinikum Jena	Jena		Germany	07740
20	EPS - Early Phase Solutions GmbH	Jena		Germany	07743
21	Hämatologie / Onkologie / Infektionskrankheiten, Palliativmedizin Städtisches Klinikum Karlsruhe	Karlsruhe		Germany	76135
22	2. Med. Klinik , Sektion f. Stammzell- + Immuntherapie Universitätsklinikum Schleswig-Holstein	Kiel		Germany	24105
23	Institut für Versorgungsforschung in der Onkologie Praxisklinik für Hämatologie und Onkologie	Koblenz		Germany	56068
24	Ärzte f. Innere Medizin Gemeinschaftspraxis f. Hämatologie u. Onkologie	Köln		Germany	50677
25	Klinik f. Innere Medizin, Klinikum der Universität zu Köln	Köln		Germany	50924
26	Medizinische Klinik und Poliklinik II Abt. Hämatologie / Onkologie, Universitätsklinikum Leipzig AÖR	Leipzig		Germany	04103
27	III. Med. Klinik, Johannes Gutenberg Universität	Mainz		Germany	55101
28	Klinikum Mannheim der Universität Heidelberg	Mannheim		Germany	68305
29	Hämatologisch-Onkologisches Institut für medizinische Service Leistungen	Mönchengladbach		Germany	41239
30	Medizinische Klinik III Klinikum der Universität München-Großhadern	München		Germany	81377
31	Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster	Münster		Germany	48129
32	Fachärzte für Innere Medizin Hämatologie und Onkologie Gemeinschaftspraxis	Münster		Germany	48149
33	Onkologie Praxis Oldenburg	Oldenburg		Germany	26121
34	Abt. Onkologie/ Hämatologie, Klinikum Oldenburg	Oldenburg		Germany	26133
35	Abteilung Hämatologie und Onkologie, Hämatologie und Onkologie, Medizinische Klinik, Klinikum Ernst v. Bergmann	Potsdam		Germany	14467
36	Klinikum der Universität Regensburg	Regensburg		Germany	93053
37	Abteilung Hämatologie und Onkologie, Medizinische Fakultät der Universität Rostock	Rostock		Germany	18057
38	Caritasklinik St. Theresia	Saarbrucken		Germany	66113
39	ms² Medizinische Statistik Saarbrücken	Saarbrucken		Germany	D-66113
40	Med. Klinik III , St. Marienkrankenhaus Siegen	Siegen		Germany	57072
41	Zentrum für Innere Medizin II Robert- Bosch-Krankenhaus GmBH	Stuttgart		Germany	D -70376
42	Krankenanstalt Mutterhaus der Borromäerinnen	Trier		Germany	54290
43	Abt. II Hämatologie, Onkologie und Immunologie Medizinische Klinik Abt.II	Tübingen		Germany	72076
44	Medizinische Universitätsklinik	Ulm		Germany	89081
45	Praxis Dres. Maintz & GroschekHämatologie / Onkologie	Wuerselen		Germany	52146
46	Med. Klinik 1, Helios Klinikum Wuppertal	Wuppertal		Germany	42283
47	Med. Klinik u. Poliklinik IIKlinikum der Universität Würzburg	Würzburg		Germany	97080
48	Hämatologisch-onkologische Praxis	Würzburg		Germany	D-97070

Sponsors and Collaborators

• Celgene Corporation

Investigators

• Principal Investigator: Axel Glasmacher, MD, University of Bonn

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celgene Corporation
• ClinicalTrials.gov Identifier: NCT00478777
• Other Study ID Numbers: CC-5013-MM-019; 2006-004532-73
• First Posted: May 25, 2007
• Last Update Posted: Nov 3, 2011
• Last Verified: Sep 1, 2011

• Keywords provided by Celgene Corporation: CC-5013; Revlimid; Lenalidomide; Celgene; Multiple Myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Lenalidomide

Study Results

Participant Flow

Recruitment Details	A total of 150 participants in 37 sites in Germany were enrolled when lenalidomide became commercially available in Germany. Study completion (end of study) was the time point when participants discontinued study drug and could switch to commercial lenalidomide.

Arm/Group Title	Lenalidomide Plus Dexamethasone
Arm/Group Description	Lenalidomide administered orally, 25 mg daily (QD) for the first 21 days of each 28-day cycle. Pulse dexamethasone administered orally, 40 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle during Cycles 1 to 4 (approximately months 1-4). Beginning with Cycle 5 (approximately month 5), dexamethasone was to be reduced to 40 mg QD for Days 1-4 of each 28 day-cycle.
Period Title: Overall Study
STARTED	150
Safety and Full Analysis Set (FAS)	144
COMPLETED	73
NOT COMPLETED	77

Baseline Characteristics

Arm/Group Title	Lenalidomide Plus Dexamethasone
Arm/Group Description	Lenalidomide administered orally, 25 mg daily (QD) for the first 21 days of each 28-day cycle. Pulse dexamethasone administered orally, 40 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle during Cycles 1 to 4 (approximately months 1-4). Beginning with Cycle 5 (approximately month 5), dexamethasone was to be reduced to 40 mg QD for Days 1-4 of each 28 day-cycle.
Overall Participants	144
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.7 (9.9)
Sex: Female, Male (Count of Participants)
Female	68 47.2%
Male	76 52.8%
Race/Ethnicity, Customized (participants) [Number]
White	142 98.6%
Other	2 1.4%
Region of Enrollment (participants) [Number]
Germany	144 100%

Outcome Measures

1. Primary Outcome

Title	Kaplan Meier Estimate for Time to Disease Progression
Description	Time to disease progression (TTP) was based on the European Group for Blood and Marrow Transplantation (EBMT) myeloma response determination criteria developed by Bladé (Bladé, 1998). TTP is a Kaplan Meier estimate of the time from randomization to the first documentation of progressive disease. Progressive disease based on increasing monoclonal paraprotein levels require a confirmatory value one week apart. Disease progression can also be based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time Frame	up to 827 days

Outcome Measure Data

Analysis Population Description

Full analysis dataset

Arm/Group Title	Lenalidomide Plus Dexamethasone
Arm/Group Description	Lenalidomide administered orally, 25 mg daily (QD) for the first 21 days of each 28-day cycle. Pulse dexamethasone administered orally, 40 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle during Cycles 1 to 4 (approximately months 1-4). Beginning with Cycle 5 (approximately month 5), dexamethasone was to be reduced to 40 mg QD for Days 1-4 of each 28 day-cycle.
Measure Participants	144
Median (95% Confidence Interval) [days]	214.0

2. Secondary Outcome

Title	Participant's Best Overall Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Criteria
Description	Best overall response was calculated as the best assessment from all cycles (including treatment discontinuation visit) and follow-up. The response rate was summarized as complete response (CR), partial response (PR), stable disease (SD), progression (PD), response not evaluable, and derived categories (PR+CR) and (PR+CR+SD). CR is negative immunofixation on both serum and urine maintained for 6 weeks straight. PR is a 50% decrease in serum paraprotein maintained for 6 weeks straight. SD is serum paraprotein values within 25% of baseline.
Time Frame	Up to 827 days

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Lenalidomide Plus Dexamethasone
Arm/Group Description	Lenalidomide administered orally, 25 mg daily (QD) for the first 21 days of each 28-day cycle. Pulse dexamethasone administered orally, 40 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle during Cycles 1 to 4 (approximately months 1-4). Beginning with Cycle 5 (approximately month 5), dexamethasone was to be reduced to 40 mg QD for Days 1-4 of each 28 day-cycle.
Measure Participants	144
Complete response (CR)	6 4.2%
Partial response (PR)	97 67.4%
Stable disease (SD)	30 20.8%
Progressive disease (PD)	3 2.1%
Not evaluable (NE)	8 5.6%
CR + PR	103 71.5%
CR + PR + SD	133 92.4%

3. Secondary Outcome

Title	Participants With Treatment-emergent Adverse Experiences (TEAEs)
Description	Counts of study participants who had treatment-emergent adverse events (TEAEs) defined as any reported AE that started on or after the first day of study drug dosing. A participant with multiple occurrences of an adverse event within a category is counted only once in that category. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) was used by investigators to assess TEAEs. Severity scale ranges from 0 (none) to 5 (death). Grade 3=severe AE; Grade 4=life threatening or disabling AE; Grade 5=death.
Time Frame	up to 8 months

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Lenalidomide Plus Dexamethasone
Arm/Group Description	Lenalidomide administered orally, 25 mg daily (QD) for the first 21 days of each 28-day cycle. Pulse dexamethasone administered orally, 40 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle during Cycles 1 to 4 (approximately months 1-4). Beginning with Cycle 5 (approximately month 5), dexamethasone was to be reduced to 40 mg QD for Days 1-4 of each 28 day-cycle.
Measure Participants	144
>=1 TEAE	139 96.5%
>=1 TEAE related to study drug	119 82.6%
>=1 NCI CTCAE grade 3 or 4 TEAE	105 72.9%
>=1 NCI CTCAE grade 3 or 4 TEAE related to drug	83 57.6%
>=1 serious AE (SAE)	79 54.9%
>=1 study drug related SAE	48 33.3%
Discontinued due to TEAE	32 22.2%
Discontinued due to TEAE related to study drug	21 14.6%
TEAE leading to dose reduction	35 24.3%
TEAE leading to dose interruption	64 44.4%
Deaths	79 54.9%

4. Secondary Outcome

Title	Time to Partial Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Determination Criteria
Description	Time to partial response is the time from randomization to a 50% decrease in serum paraprotein maintained for six weeks straight. This was determined by free light chain concentrations which were taken every two weeks during the treatment phase of the trial.
Time Frame	up to 827 days

Outcome Measure Data

Analysis Population Description

Values for the free light chain concentrations were determined to be invalid.

Arm/Group Title	Lenalidomide Plus Dexamethasone
Arm/Group Description	Lenalidomide administered orally, 25 mg daily (QD) for the first 21 days of each 28-day cycle. Pulse dexamethasone administered orally, 40 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle during Cycles 1 to 4 (approximately months 1-4). Beginning with Cycle 5 (approximately month 5), dexamethasone was to be reduced to 40 mg QD for Days 1-4 of each 28 day-cycle.
Measure Participants	0

Adverse Events

Time Frame	Up to 8 months
Arm/Group Title	Lenalidomide Plus Dexamethasone
Arm/Group Description	Lenalidomide administered orally, 25 mg daily (QD) for the first 21 days of each 28-day cycle. Pulse dexamethasone administered orally, 40 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle during Cycles 1 to 4 (approximately months 1-4). Beginning with Cycle 5 (approximately month 5), dexamethasone was to be reduced to 40 mg QD for Days 1-4 of each 28 day-cycle.
All Cause Mortality
	Lenalidomide Plus Dexamethasone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lenalidomide Plus Dexamethasone
	Affected / at Risk (%)	# Events
Total	79/144 (54.9%)
Blood and lymphatic system disorders
Anaemia	5/144 (3.5%)
Neutropenia	4/144 (2.8%)
Thrombocytopenia	3/144 (2.1%)
Febrile neutropenia	2/144 (1.4%)
Leukopenia	2/144 (1.4%)
Pancytopenia	1/144 (0.7%)
Cardiac disorders
Cardiac failure	3/144 (2.1%)
Atrial fibrillation	2/144 (1.4%)
Tachyarrhythmia	2/144 (1.4%)
Angina pectoris	1/144 (0.7%)
Arrhythmia	1/144 (0.7%)
Atrial flutter	1/144 (0.7%)
Bundle branch block right	1/144 (0.7%)
Extrasystoles	1/144 (0.7%)
Myocardial infarction	1/144 (0.7%)
Pericardial effusion	1/144 (0.7%)
Ventricular fibrillation	1/144 (0.7%)
Ventricular tachycardia	1/144 (0.7%)
Congenital, familial and genetic disorders
Epidermolysis bullosa	1/144 (0.7%)
Factor VIII deficiency	1/144 (0.7%)
Ear and labyrinth disorders
Vertigo	3/144 (2.1%)
Eye disorders
Vision blurred	1/144 (0.7%)
Gastrointestinal disorders
Diarrhoea	5/144 (3.5%)
Nausea	3/144 (2.1%)
Haemorrhoidal haemorrhage	2/144 (1.4%)
Vomiting	2/144 (1.4%)
Abdominal pain upper	1/144 (0.7%)
Anal haemorrhage	1/144 (0.7%)
Diarrhoea haemorrhagic	1/144 (0.7%)
Duodenitis	1/144 (0.7%)
Gastrointestinal haemorrhage	1/144 (0.7%)
Large intestinal perforation	1/144 (0.7%)
Subileus	1/144 (0.7%)
Tooth disorder	1/144 (0.7%)
General disorders
Pyrexia	14/144 (9.7%)
General physical health deterioration	6/144 (4.2%)
Asthenia	2/144 (1.4%)
Multi-organ failure	2/144 (1.4%)
Chills	1/144 (0.7%)
Fatigue	1/144 (0.7%)
Gait disturbance	1/144 (0.7%)
Orthostatic intolerance	1/144 (0.7%)
Pain	1/144 (0.7%)
Immune system disorders
Acute graft versus host disease in intestine	1/144 (0.7%)
Graft versus host disease	1/144 (0.7%)
Infections and infestations
Pneumonia	8/144 (5.6%)
Sepsis	6/144 (4.2%)
Upper respiratory tract infection	2/144 (1.4%)
Bronchitis	1/144 (0.7%)
Febrile infection	1/144 (0.7%)
Gastrointestinal infection	1/144 (0.7%)
Herpes zoster	1/144 (0.7%)
Infection	1/144 (0.7%)
Lung infection	1/144 (0.7%)
Respiratory tract infection	1/144 (0.7%)
Tooth infection	1/144 (0.7%)
Urinary tract infection	1/144 (0.7%)
Urosepsis	1/144 (0.7%)
Injury, poisoning and procedural complications
Humerus fracture	3/144 (2.1%)
Femoral neck fracture	1/144 (0.7%)
Investigations
Haemoglobin decreased	1/144 (0.7%)
Platelet count decreased	1/144 (0.7%)
Protein total increased	1/144 (0.7%)
White blood cell count increased	1/144 (0.7%)
Metabolism and nutrition disorders
Hypercalcaemia	2/144 (1.4%)
Hyperglycaemia	2/144 (1.4%)
Dehydration	1/144 (0.7%)
Diabetes mellitus	1/144 (0.7%)
Electrolyte imbalance	1/144 (0.7%)
Hyperkalaemia	1/144 (0.7%)
Hypocalcaemia	1/144 (0.7%)
Musculoskeletal and connective tissue disorders
Back pain	3/144 (2.1%)
Bone pain	2/144 (1.4%)
Muscle spasms	2/144 (1.4%)
Arthritis	1/144 (0.7%)
Osteolysis	1/144 (0.7%)
Pain in extremity	1/144 (0.7%)
Pathological fracture	1/144 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma	6/144 (4.2%)
Colon cancer	1/144 (0.7%)
Colon adenoma	1/144 (0.7%)
Leukaemia plasmacytic	1/144 (0.7%)
Squamous cell carcinoma of skin	1/144 (0.7%)
Tumour pain	1/144 (0.7%)
Nervous system disorders
Syncope	3/144 (2.1%)
Dizziness	2/144 (1.4%)
Grand mal convulsion	1/144 (0.7%)
Headache	1/144 (0.7%)
Neurological symptom	1/144 (0.7%)
Neuromyopathy	1/144 (0.7%)
Syncope vasovagal	1/144 (0.7%)
Tremor	1/144 (0.7%)
Psychiatric disorders
Confusional state	2/144 (1.4%)
Depression	1/144 (0.7%)
Disorientation	1/144 (0.7%)
Mental disorder due to a general medical condition	1/144 (0.7%)
Psychotic disorder	1/144 (0.7%)
Renal and urinary disorders
Renal failure	4/144 (2.8%)
Renal failure acute	3/144 (2.1%)
Renal impairment	1/144 (0.7%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	4/144 (2.8%)
Dyspnoea	3/144 (2.1%)
Respiratory failure	2/144 (1.4%)
Pleural effusion	1/144 (0.7%)
Pulmonary oedema	1/144 (0.7%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/144 (0.7%)
Vascular disorders
Thrombosis	3/144 (2.1%)
Hypotension	2/144 (1.4%)
Circulatory collapse	1/144 (0.7%)
Deep vein thrombosis	1/144 (0.7%)
Subclavian vein thrombosis	1/144 (0.7%)
Other (Not Including Serious) Adverse Events
	Lenalidomide Plus Dexamethasone
	Affected / at Risk (%)	# Events
Total	129/144 (89.6%)
Blood and lymphatic system disorders
Leukopenia	28/144 (19.4%)
Thromboyctopenia	25/144 (17.4%)
Anaemia	15/144 (10.4%)
Lymphopenia	14/144 (9.7%)
Neutropenia	12/144 (8.3%)
Gastrointestinal disorders
Diarrhoea	22/144 (15.3%)
Constipation	20/144 (13.9%)
Nausea	9/144 (6.3%)
General disorders
Fatigue	33/144 (22.9%)
Oedema peripheral	19/144 (13.2%)
Pyrexia	18/144 (12.5%)
Infections and infestations
Nasopharyngitis	12/144 (8.3%)
Urinary tract infection	9/144 (6.3%)
Investigations
Haemoglobin decreased	13/144 (9%)
C-reactive protein increased	12/144 (8.3%)
Metabolism and nutrition disorders
Hyperglycaemia	9/144 (6.3%)
Musculoskeletal and connective tissue disorders
Muscle spasms	35/144 (24.3%)
Back pain	13/144 (9%)
Arthralgia	12/144 (8.3%)
Pain in extremity	11/144 (7.6%)
Muscular weakness	9/144 (6.3%)
Bone pain	8/144 (5.6%)
Nervous system disorders
Dizziness	17/144 (11.8%)
Tremor	15/144 (10.4%)
Polyneuropathy	14/144 (9.7%)
Paraesthesia	8/144 (5.6%)
Psychiatric disorders
Insomnia	15/144 (10.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	9/144 (6.3%)
Cough	8/144 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Multicenter publication must include input from investigators and Celgene, agreement to be established before publication. It has priority over subset (single center) publication, for duration of 1 year after study completion. Individual investigators have publication right after multicenter publication is complete (or 1 year after study completion), whichever is first. In this case, Celgene has the right to comment and right to ask delay of publication for 90 days.