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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01324947




Trial ID
NCT01324947
Ethics application status
Date submitted
27/03/2011
Date registered
27/03/2011
Date last updated
28/10/2016

Titles & IDs
Public title
Study to Evaluate the Safety and Efficacy of Pomalidomide Monotherapy in Subjects With Refractory or Relapsed Refractory Multiple Myeloma
Scientific title
Open-label, Multi-center, Single Arm Study For The Safety And Efficacy Of Pomalidomide Monotherapy For Subjects With Refractory Or Relapsed And Refractory Multiple Myeloma. A Companion Study For Clinical Trial CC-4047-MM003
Secondary ID [1] 0 0
2010-023343-16
Secondary ID [2] 0 0
CC-4047-MM-003/C
Universal Trial Number (UTN)
Trial acronym
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

Experimental: Pomalidomide - Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity


Treatment: Drugs: pomalidomide
Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria Based on Investigator Assessment - Objective response defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on Investigator Assessment.
SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; PR: =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. A =50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a =50% reduction in plasma cells in place of M-protein if baseline was =30%. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.
Timepoint [1] 0 0
From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum time on follow-up was 141.1 weeks.
Secondary outcome [1] 0 0
Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria Based on Investigator Assessment - Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the CR and requires all of the following:
Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days.
<5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed.
No increase in size or number of lytic bone lesions.
Disappearance of soft tissue plasmacytomas.
PR requires all of the following:
=50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days.
Reduction in 24-hour urinary light chain extraction by =90% or to <200 mg, maintained at least 42 days.
For patients with non-secretory myeloma, =50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days.
Timepoint [1] 0 0
From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum time on follow-up was 141.1 weeks.
Secondary outcome [2] 0 0
Number of Participants With Adverse Events and Type of Adverse Events - An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that:
Results in death;
Is life-threatening;
Requires or prolongs existing inpatient hospitalization;
Results in persistent or significant disability/incapacity;
Is a congenital anomaly/birth defect;
Constitutes an important medical event.
The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0):
Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required);-Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death
Timepoint [2] 0 0
From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 31 July 2014. Maximum time on treatment was 94.1 weeks.
Secondary outcome [3] 0 0
Kaplan Meier Estimates for Progression Free Survival (PFS) by Investigator Based on IMWG - Progression-free survival was calculated as the time from randomization to disease progression as determined by the Investigator based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier.
Progressive disease requires 1 of the following:
Increase of = 25% from nadir in:
Serum M-component (absolute increase = 0.5 g/dl)
Urine M-component (absolute increase = 200 mg/24 hours)
In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl)
Bone marrow plasma cell percentage (absolute % = 10%)
Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas.
Timepoint [3] 0 0
From randomization through the follow-up phase; Maximum duration of follow-up for PFS was 90.3 weeks.
Secondary outcome [4] 0 0
Kaplan-Meier Estimate for Time to Progression (TTP) Based on Investigator Assessment Using IMWG Criteria - Time to progression (TTP) was calculated as the time from randomization to the first documented progression confirmed by the investigator and based on the International Myeloma Working Group Uniform Response criteria (IMWG).
Progressive disease requires 1 of the following:
Increase of = 25% from nadir in:
Serum M-component (absolute increase = 0.5 g/dl)
Urine M-component (absolute increase = 200 mg/24 hours)
In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl)
Bone marrow plasma cell percentage (absolute % = 10%)
Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas.
Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
Timepoint [4] 0 0
From randomization through the follow-up phase; up to the data-cut off of 31 July 2014; Maximum time to progression follow-up was 90.3 weeks.
Secondary outcome [5] 0 0
Kaplan-Meier Estimate Duration of Response Based on Investigator Assessment Using IMWG Criteria - Duration of Response (calculated for responders only) is defined as the time from the initial documented response (partial response or better) to confirmed disease progression by the investigator based on IMWG criteria.
Timepoint [5] 0 0
From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum duration of response follow-up was 90.3 weeks.
Secondary outcome [6] 0 0
Kaplan-Meier Estimate for Overall Survival - Overall survival was calculated as the time from randomization to death from any cause. Overall survival was 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.
Timepoint [6] 0 0
From randomization through the follow-up phase; Maximum time on follow-up was 141.1 weeks.
Secondary outcome [7] 0 0
Time to Response Based on IMWG and Assessed by the Investigator - Time to Response was calculated as the time from enrollment to the initial response (PR or better) based on IMWG and assessed by the investigator.
Timepoint [7] 0 0
From randomization through the follow-up phase; up to the data-cut off of 31 July 2014; Maximum time to response was 23.1 weeks

Eligibility
Key inclusion criteria
1. Subjects with refractory or relapsed and refractory multiple myeloma who were enrolled
in Study CC-4047-MM-003 and discontinued study therapy with dexamethasone alone
(Treatment Arm B) after at least starting the second cycle of dexamethasone treatment
and due to development of documented disease progression according to the
International Myeloma Working Group (IMWG) criteria and as decided by an Independent
Review Adjudication Committee (IRAC).

2. Must be = 18 years at the time of signing the informed consent form.

3. The subject must understand and voluntarily sign an informed consent document prior to
any study related assessments/procedures being conducted. The only exception is if a
skeletal survey was performed within 90 days prior to the start of Cycle 1, then a new
survey will not be required.

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

5. Subjects must have documented diagnosis of multiple myeloma and have measurable
disease (serum M-protein = 0.5g/dL or urine M-protein = 200 mg/24 hours).

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

7. Females of childbearing potential (FCBP†) must agree to utilize two reliable forms of
contraception simultaneously or practice true abstinence [when this is in line with
the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar,
ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable
methods of contraception]from heterosexual contact for at least 28 days before
starting study drug, while participating in the study (including dose interruptions),
and for at least 28 days after study treatment discontinuation and must agree to
regular pregnancy testing during this timeframe.

8. Females must agree to abstain from breastfeeding during study participation and 28
days after study discontinuation.

9. Males must agree to either use a latex condom during any sexual contact with FCBP or
practice true abstinence [when this is in line with the preferred and usual lifestyle
of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of contraception]
while participating in the study and for 28 days following discontinuation from this
study, even if he has undergone a successful vasectomy. .

10. Males must also agree to refrain from donating semen or sperm while on pomalidomide
and for 28 days after discontinuation from this study treatment.

11. All subjects must agree to refrain from donating blood while on study drug and for 28
days after discontinuation from this study treatment.

12. All subjects must agree not to share study medication
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

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

1. Subjects with multiple myeloma who were not treated as a part of Study
CC-4047-MM-003 (Arm B).

2. Subjects who received any anti-myeloma or anti-cancer therapies within the last
14 days of wash-out period before initiation of study treatment.

3. Subjects who discontinued CC-4047-MM-003 study =120 days.

4. Subjects who initiate another anti-myeloma therapy from the time of disease
progression on study CC-4047-MM-003 to the time of treatment initiation in the
companion study.

5. 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; or a platelet count < 30,000/µL for
subjects in whom = 50% of bone marrow nucleated cells are plasma cells

- Creatinine Clearance < 45 mL/min according to Cockcroft-Gault formula (If
creatinine clearance calculated from the 24-hour urine sample is =45 ml/min,
patient will qualify for the trial)

- Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L);

- Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant
human erythropoietin use is permitted)

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

- Serum total bilirubin > 2.0 mg/dL (34.2 µmol/L); or > 3.0 x ULN for subjects
with hereditary benign hyperbilirubinaemia

6. Prior history of malignancies, other than Multiple Myeloma (MM), unless the
subject has been free of the disease for = 5 years. Exceptions include the
following:

- Basal or Squamous cell carcinoma of the skin

- Carcinoma in situ of the cervix or breast

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

7. Hypersensitivity to thalidomide or lenalidomide. (This includes = Grade 3 rash
during prior thalidomide or lenalidomide therapy).

8. Peripheral neuropathy = Grade 2.

9. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood
stem cell transplant less than 12 months prior to initiation of study treatment
and who have not discontinued immunosuppressive treatment for at least 4 weeks
prior to initiation of study treatment and are currently dependent on such
treatment.

10. Subjects who are planning for or who are eligible for stem cell transplant.

11. Subjects with any one of the following:

- Congestive heart failure (NY Heart Association Class III or IV)

- Myocardial infarction within 12 months prior to starting study treatment

- Unstable or poorly controlled angina pectoris, including Prinzmetal variant
angina pectoris

12. Subjects who received any of the following within the last 14 days of initiation
of study treatment:

- Plasmapheresis

- Major surgery (kyphoplasty is not considered major surgery)

- Radiation therapy

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

14. Subjects with chronic conditions such as rheumatoid arthritis, multiple sclerosis
and lupus, which likely need additional steroid or immunosuppressive treatments
in addition to the study treatment.

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

16. Incidence of gastrointestinal disease that may significantly alter the absorption
of pomalidomide.

17. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.

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

19. Pregnant or breastfeeding females.

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

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Single group
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - SA Pathology Haematology - Adelaide
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Haematology - Brisbane
Recruitment hospital [3] 0 0
Royal Prince Alfred Hospital - Institute of Haematology - Camperdown
Recruitment hospital [4] 0 0
Peter McCallum Cancer Institute - Directorate of Cancer Medicine - East Melbourne
Recruitment hospital [5] 0 0
Frankston Hospital-Peninsula Health - Oncology Day Unit - Frankston
Recruitment hospital [6] 0 0
The Alfred Hospital - Malignant Haematology & Stem Cell Transplantation - Melbourne
Recruitment hospital [7] 0 0
Calvary Mater Newcastle - Haematology - Waratah
Recruitment hospital [8] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [9] 0 0
Wollongong Hospital - Haematology - Wollongong
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne
Recruitment postcode(s) [5] 0 0
3199 - Frankston
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment postcode(s) [7] 0 0
2298 - Waratah
Recruitment postcode(s) [8] 0 0
3690 - Wodonga
Recruitment postcode(s) [9] 0 0
2500 - Wollongong
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Gent
Country [2] 0 0
Belgium
State/province [2] 0 0
Leuven
Country [3] 0 0
Belgium
State/province [3] 0 0
Yvoir
Country [4] 0 0
Canada
State/province [4] 0 0
Alberta
Country [5] 0 0
Canada
State/province [5] 0 0
British Columbia
Country [6] 0 0
Canada
State/province [6] 0 0
Nova Scotia
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
Czech Republic
State/province [9] 0 0
Prague
Country [10] 0 0
Denmark
State/province [10] 0 0
Aalborg
Country [11] 0 0
Denmark
State/province [11] 0 0
Aarhus
Country [12] 0 0
Denmark
State/province [12] 0 0
Odense
Country [13] 0 0
Denmark
State/province [13] 0 0
Vejle
Country [14] 0 0
France
State/province [14] 0 0
Angers
Country [15] 0 0
France
State/province [15] 0 0
Bayonne
Country [16] 0 0
France
State/province [16] 0 0
La Roche
Country [17] 0 0
France
State/province [17] 0 0
Lille
Country [18] 0 0
France
State/province [18] 0 0
Marseille
Country [19] 0 0
France
State/province [19] 0 0
Nantes
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
France
State/province [21] 0 0
Pessac
Country [22] 0 0
France
State/province [22] 0 0
Pierre-Benite
Country [23] 0 0
France
State/province [23] 0 0
Toulouse
Country [24] 0 0
France
State/province [24] 0 0
Tours
Country [25] 0 0
France
State/province [25] 0 0
Vandoeuvre-les-Nancy
Country [26] 0 0
Germany
State/province [26] 0 0
Dresden
Country [27] 0 0
Germany
State/province [27] 0 0
Essen
Country [28] 0 0
Germany
State/province [28] 0 0
Hamburg
Country [29] 0 0
Germany
State/province [29] 0 0
Heidelberg
Country [30] 0 0
Germany
State/province [30] 0 0
Jena
Country [31] 0 0
Germany
State/province [31] 0 0
Leipzig
Country [32] 0 0
Germany
State/province [32] 0 0
Münster
Country [33] 0 0
Germany
State/province [33] 0 0
Tübingen
Country [34] 0 0
Germany
State/province [34] 0 0
Ulm
Country [35] 0 0
Germany
State/province [35] 0 0
Würzburg
Country [36] 0 0
Greece
State/province [36] 0 0
Athens
Country [37] 0 0
Italy
State/province [37] 0 0
Bologna
Country [38] 0 0
Italy
State/province [38] 0 0
Genova
Country [39] 0 0
Italy
State/province [39] 0 0
Napoli
Country [40] 0 0
Italy
State/province [40] 0 0
Orbassano
Country [41] 0 0
Italy
State/province [41] 0 0
Padova
Country [42] 0 0
Italy
State/province [42] 0 0
Piacenza
Country [43] 0 0
Italy
State/province [43] 0 0
Reggio Emilia
Country [44] 0 0
Italy
State/province [44] 0 0
Roma
Country [45] 0 0
Italy
State/province [45] 0 0
Torino
Country [46] 0 0
Netherlands
State/province [46] 0 0
Amsterdam
Country [47] 0 0
Netherlands
State/province [47] 0 0
Rotterdam
Country [48] 0 0
Netherlands
State/province [48] 0 0
Utrecht
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Moscow
Country [50] 0 0
Russian Federation
State/province [50] 0 0
St. Petersburg
Country [51] 0 0
Spain
State/province [51] 0 0
Badalona
Country [52] 0 0
Spain
State/province [52] 0 0
Barcelona
Country [53] 0 0
Spain
State/province [53] 0 0
Guipúzcoa
Country [54] 0 0
Spain
State/province [54] 0 0
Madrid
Country [55] 0 0
Spain
State/province [55] 0 0
Salamanca
Country [56] 0 0
Spain
State/province [56] 0 0
Santander
Country [57] 0 0
Spain
State/province [57] 0 0
Valencia
Country [58] 0 0
Sweden
State/province [58] 0 0
Goteborg
Country [59] 0 0
Sweden
State/province [59] 0 0
Stockholm
Country [60] 0 0
Sweden
State/province [60] 0 0
Uppsala
Country [61] 0 0
Switzerland
State/province [61] 0 0
Bern
Country [62] 0 0
Switzerland
State/province [62] 0 0
Genève
Country [63] 0 0
Switzerland
State/province [63] 0 0
Zürich
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Bournemouth
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Leeds
Country [66] 0 0
United Kingdom
State/province [66] 0 0
London
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Newcastle Upon Tyne
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Nottingham
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Plymouth
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Sheffield
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Surrey
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Wolverhampton

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy and safety of pomalidomide monotherapy
in subjects with refractory or relapsed and refractory multiple myeloma who were enrolled in
study CC-4047-MM-003 (NCT01311687) and discontinued treatment with high-dose dexamethasone
due to disease progression.
Trial website
https://clinicaltrials.gov/show/NCT01324947
Trial related presentations / publications
Moreau P, Weisel KC, Song KW, Gibson CJ, Saunders O, Sternas LA, Hong K, Zaki MH, Dimopoulos MA. Relationship of response and survival in patients with relapsed and refractory multiple myeloma treated with pomalidomide plus low-dose dexamethasone in the MM-003 trial randomized phase III trial (NIMBUS). Leuk Lymphoma. 2016 Dec;57(12):2839-2847. Epub 2016 May 13.
Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-1066. doi: 10.1016/S1470-2045(13)70380-2. Epub 2013 Sep 3.
Public notes

Contacts
Principal investigator
Name 0 0
Mohamed Zaki, MD, PhD
Address 0 0
Celgene Corporation
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