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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01311687




Registration number
NCT01311687
Ethics application status
Date submitted
8/03/2011
Date registered
9/03/2011
Date last updated
24/10/2018

Titles & IDs
Public title
A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Subjects With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study
Scientific title
A Phase 3, Muticenter, Randomized, Open-label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-dose Dexamethasone Versus High-dose Dexamethasone in Subjects With Refractory or Relapsed and Refractory Multiple Myeloma
Secondary ID [1] 0 0
2010-019820-30
Secondary ID [2] 0 0
CC-4047-MM-003
Universal Trial Number (UTN)
Trial acronym
NIMBUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - pomalidomide
Treatment: Drugs - Dexamethasone

Experimental: Pomalidomide + Low-Dose Dexamethasone - Participants received 4 mg pomalidomide administered by mouth on Days 1 to 21 of each 28-day treatment cycle and 40 mg dexamethasone (or 20 mg for participants > 75 years of age) administered by mouth once per day on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression.

Active Comparator: High-Dose Dexamethasone - Participants received 40 mg dexamethasone (or 20 mg for participants > 75 years of age) administered by mouth once per day on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day treatment cycle until disease progression.


Treatment: Drugs: pomalidomide
4 mg pomalidomide capsules administered orally

Treatment: Drugs: Dexamethasone
40 mg dexamethasone (or 20 mg for participants > 75 years of age) tablets administered orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) - Primary Analysis
Timepoint [1] 0 0
From randomization until the data cut-off date of 07 September 2012. Maximum duration of follow-up for PFS assessments was 57 weeks.
Primary outcome [2] 0 0
Progression-free Survival (PFS) With a Later Cut-off Date
Timepoint [2] 0 0
From randomization until the data cut-off date of 01 March 2013. Maximum duration of follow-up for PFS assessments was 74 weeks.
Secondary outcome [1] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [1] 0 0
From first dose of study drug through to 30 days after the last dose as of the end of the study (29 August 2017); maximum time on treatment was 297, 269, and 239 weeks in the Pomalidomide + LD-Dex, HD-Dex, and cross-over groups respectively.
Secondary outcome [2] 0 0
Overall Survival - Primary Analysis
Timepoint [2] 0 0
From randomization until the data cut-off date of 07 September 2012. Maximum time on follow-up for survival was 70 weeks.
Secondary outcome [3] 0 0
Overall Survival With a Later Cut-off Date
Timepoint [3] 0 0
From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up for survival was 93 weeks.
Secondary outcome [4] 0 0
Overall Survival Based on the Final Dataset
Timepoint [4] 0 0
From randomization until the data cut-off date of 29 August 2017. Maximum time on follow-up for survival was 324 weeks.
Secondary outcome [5] 0 0
Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria
Timepoint [5] 0 0
From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Secondary outcome [6] 0 0
Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria
Timepoint [6] 0 0
From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Secondary outcome [7] 0 0
Time to Progression
Timepoint [7] 0 0
From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Secondary outcome [8] 0 0
Time to Response
Timepoint [8] 0 0
From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Secondary outcome [9] 0 0
Duration of Response
Timepoint [9] 0 0
From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Secondary outcome [10] 0 0
Time to the First Hemoglobin Improvement
Timepoint [10] 0 0
From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Secondary outcome [11] 0 0
Time to Improvement in Bone Pain
Timepoint [11] 0 0
From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Secondary outcome [12] 0 0
Time to Improvement in Renal Function
Timepoint [12] 0 0
From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Secondary outcome [13] 0 0
Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status
Timepoint [13] 0 0
From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Secondary outcome [14] 0 0
Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain
Timepoint [14] 0 0
Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Secondary outcome [15] 0 0
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Timepoint [15] 0 0
Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Secondary outcome [16] 0 0
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain
Timepoint [16] 0 0
Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Secondary outcome [17] 0 0
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain
Timepoint [17] 0 0
Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Secondary outcome [18] 0 0
Change From Baseline in the EORTC QLQ-C30 Pain Domain
Timepoint [18] 0 0
Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Secondary outcome [19] 0 0
Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms
Timepoint [19] 0 0
Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Secondary outcome [20] 0 0
Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain
Timepoint [20] 0 0
Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Secondary outcome [21] 0 0
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score
Timepoint [21] 0 0
Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Secondary outcome [22] 0 0
Time to First Worsening of Quality of Life (QOL) Domains
Timepoint [22] 0 0
Assessed on Day 1 of the first 6 treatment cycles.

Eligibility
Key inclusion criteria
- Must be = 18 years of age

- Subjects must have documented diagnosis of multiple myeloma and have measurable
disease

- Subjects must have undergone prior treatment with = 2 treatment lines of anti-myeloma
therapy

- Subjects must have either refractory or relapsed and refractory disease defined as
documented disease progression during or within 60 days of completing their last
myeloma therapy

- All subjects must have received at least 2 consecutive cycles of prior treatment that
included lenalidomide and bortezomib

- All subjects must have failed treatment with both lenalidomide and bortezomib in one
of the following ways: 1) Documented progressive disease on or within 60 days of
completing treatment with lenalidomide and/or bortezomib, or 2) In case of prior
response [= partial response (PR)] to lenalidomide or bortezomib, subjects must have
relapsed within 6 months after stopping treatment with lenalidomide and/or
bortezomib-containing regimens, or 3) Subjects who have not had a = minimal response
(MR) and have developed intolerance/toxicity after a minimum of two cycles of
lenalidomide- and/or bortezomib-containing regimen

- Patients must have received adequate prior alkylator therapy

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

- Females of childbearing potential (FCBP) must not become pregnant for 28 days prior to
initiation of study drug, during the study, and for 28 days after discontinuation

- Females must agree to abstain from breastfeeding during study participation and 28
days after study drug discontinuation

- Males must agree to use a latex condom during any sexual during the study and for 28
days following discontinuation from this study

- Males must also agree to refrain from donating semen or sperm while on pomalidomide
and for 28 days after discontinuation from this study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any of the following laboratory abnormalities:

- Absolute neutrophil count (ANC) < 1,000/µL

- Platelet count < 75,000/ µL for subjects in whom < 50% of bone marrow nucleated
cells are plasma cells

- Creatinine clearance < 45 mL/min

- Corrected serum calcium > 14 mg/dL

- Hemoglobin = 8 g/dL

- Serum glutamic oxaloacetic transaminase (SGOT)/ aspartate aminotransferase (AST)
or transaminase, serum glutamic pyruvic (SGPT)/ alanine aminotransferase (ALT) >
3.0 x upper limit of normal (ULN)

- Serum total bilirubin > 2.0 mg/dL

- Previous therapy with pomalidomide

- Hypersensitivity to thalidomide, lenalidomide, or dexamethasone

- Resistance to high-dose dexamethasone used in the last line of therapy

- Peripheral neuropathy = Grade 2

- Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem
cell transplant

- Subjects who are planning for or who are eligible for stem cell transplant

- Subjects with any one of the following: 1) Congestive heart failure, 2) Myocardial
infarction within 12 months prior to starting study treatment, 3) Unstable or poorly
controlled angina pectoris, including Prinzmetal variant angina pectoris

- Subjects who received any of the following within the last 14 days of initiation of
study treatment: 1) Plasmapheresis, 2) Major surgery, 3) Radiation therapy, 4) Use of
any anti-myeloma drug therapy

- Use of any investigational agents within 28 days or 5 half-lives (whichever is longer)
of treatment

- Subjects with conditions requiring chronic steroid or immunosuppressive treatment

- Any condition including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study

- Incidence of gastrointestinal disease that may significantly alter the absorption of
pomalidomide

- Subjects unable or unwilling to undergo antithrombotic prophylactic treatment

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subjects from signing the informed consent form

- Pregnant or breastfeeding females

- Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis A,
B, or C

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/03/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/08/2017
Sample size
Target
Accrual to date
Final
455
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [3] 0 0
Frankston Hospital - Frankston
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [5] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [6] 0 0
Alfred hospital - Melbourne
Recruitment hospital [7] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [8] 0 0
Calvary Mater Hospital - Waratah
Recruitment hospital [9] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [10] 0 0
Wollongong Hospital - Wollongong
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
QLD4102 - Brisbane
Recruitment postcode(s) [5] 0 0
2050 - Camperdown
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment postcode(s) [8] 0 0
NSW 2298 - Waratah
Recruitment postcode(s) [9] 0 0
3690 - Wodonga
Recruitment postcode(s) [10] 0 0
2500 - Wollongong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Minnesota
Country [2] 0 0
Belgium
State/province [2] 0 0
Gent
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Belgium
State/province [4] 0 0
Yvoir
Country [5] 0 0
Canada
State/province [5] 0 0
Alberta
Country [6] 0 0
Canada
State/province [6] 0 0
British Columbia
Country [7] 0 0
Canada
State/province [7] 0 0
Nova Scotia
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
Czechia
State/province [10] 0 0
Praha 2
Country [11] 0 0
Denmark
State/province [11] 0 0
Aalborg
Country [12] 0 0
Denmark
State/province [12] 0 0
Arhus C
Country [13] 0 0
Denmark
State/province [13] 0 0
Odense C
Country [14] 0 0
Denmark
State/province [14] 0 0
Vejle
Country [15] 0 0
France
State/province [15] 0 0
Angers Cedex 01
Country [16] 0 0
France
State/province [16] 0 0
Bayonne
Country [17] 0 0
France
State/province [17] 0 0
La Roche sur Yon
Country [18] 0 0
France
State/province [18] 0 0
Lille
Country [19] 0 0
France
State/province [19] 0 0
Marseille Cedex 9
Country [20] 0 0
France
State/province [20] 0 0
Nantes Cedex 1
Country [21] 0 0
France
State/province [21] 0 0
Paris, Cedex 10
Country [22] 0 0
France
State/province [22] 0 0
Paris
Country [23] 0 0
France
State/province [23] 0 0
Pessac
Country [24] 0 0
France
State/province [24] 0 0
Pierre Bénite
Country [25] 0 0
France
State/province [25] 0 0
Tours
Country [26] 0 0
France
State/province [26] 0 0
Tulouse Cedex 9
Country [27] 0 0
France
State/province [27] 0 0
Vandoeuvre
Country [28] 0 0
Germany
State/province [28] 0 0
Dresden
Country [29] 0 0
Germany
State/province [29] 0 0
Essen
Country [30] 0 0
Germany
State/province [30] 0 0
Hamburg
Country [31] 0 0
Germany
State/province [31] 0 0
Heidelberg
Country [32] 0 0
Germany
State/province [32] 0 0
Jena
Country [33] 0 0
Germany
State/province [33] 0 0
Leipzig
Country [34] 0 0
Germany
State/province [34] 0 0
Tübingen
Country [35] 0 0
Germany
State/province [35] 0 0
Ulm
Country [36] 0 0
Germany
State/province [36] 0 0
Wuerzburg
Country [37] 0 0
Greece
State/province [37] 0 0
Athens
Country [38] 0 0
Italy
State/province [38] 0 0
Bologna
Country [39] 0 0
Italy
State/province [39] 0 0
Genova
Country [40] 0 0
Italy
State/province [40] 0 0
Napoli
Country [41] 0 0
Italy
State/province [41] 0 0
Orbassano
Country [42] 0 0
Italy
State/province [42] 0 0
Padova
Country [43] 0 0
Italy
State/province [43] 0 0
Placenza
Country [44] 0 0
Italy
State/province [44] 0 0
Reggio Emilia
Country [45] 0 0
Italy
State/province [45] 0 0
Rome
Country [46] 0 0
Italy
State/province [46] 0 0
Torino
Country [47] 0 0
Netherlands
State/province [47] 0 0
Amsterdam
Country [48] 0 0
Netherlands
State/province [48] 0 0
Rotterdam
Country [49] 0 0
Netherlands
State/province [49] 0 0
Utrecht
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Moscow
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Saint Petersburg
Country [52] 0 0
Russian Federation
State/province [52] 0 0
St. Petersburg
Country [53] 0 0
Spain
State/province [53] 0 0
Badalona (Barcelona)
Country [54] 0 0
Spain
State/province [54] 0 0
Barcelona
Country [55] 0 0
Spain
State/province [55] 0 0
Madrid
Country [56] 0 0
Spain
State/province [56] 0 0
Salamanca
Country [57] 0 0
Spain
State/province [57] 0 0
San Sebastián (Guipuzcoa)
Country [58] 0 0
Spain
State/province [58] 0 0
Santander
Country [59] 0 0
Spain
State/province [59] 0 0
Valencia
Country [60] 0 0
Sweden
State/province [60] 0 0
Göteborg
Country [61] 0 0
Sweden
State/province [61] 0 0
Lund
Country [62] 0 0
Sweden
State/province [62] 0 0
Stockholm
Country [63] 0 0
Sweden
State/province [63] 0 0
Uppsala
Country [64] 0 0
Switzerland
State/province [64] 0 0
Berne
Country [65] 0 0
Switzerland
State/province [65] 0 0
Geneva
Country [66] 0 0
Switzerland
State/province [66] 0 0
Zürich
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Bournemouth
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Leeds
Country [69] 0 0
United Kingdom
State/province [69] 0 0
London
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Newcastle Upon Tyne
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Nottingham
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Plymouth
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Sheffield
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Sutton-Surrey
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to compare efficacy and safety of pomalidomide in combination
with low-dose dexamethasone versus high-dose dexamethasone in subjects with refractory or
relapsed and refractory multiple myeloma.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01311687
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Lars Sternas, MD, PhD
Address 0 0
Celgene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01311687