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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01178281




Registration number
NCT01178281
Ethics application status
Date submitted
15/07/2010
Date registered
10/08/2010
Date last updated
17/07/2019

Titles & IDs
Public title
Study of Pomalidomide in Persons With Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence
Scientific title
A Phase-3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Compare Efficacy and Safety of Pomalidomide in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis and Red Blood Cell-Transfusion-Dependence
Secondary ID [1] 0 0
2010-018965-42
Secondary ID [2] 0 0
CC-4047-MF-002
Universal Trial Number (UTN)
Trial acronym
RESUME
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Myelofibrosis 0 0
MPN-associated Myelofibrosis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pomalidomide 0.5 mg
Treatment: Drugs - Placebo
Treatment: Drugs - Pomalidomide

Experimental: Pomalidomide 0.5 mg - Participants received pomalidomide 0.5 mg/day by mouth for at least 168 days unless there were unacceptable side effects or disease progression.

Participants who were RBC-transfusion independent or experienced clinical benefit (defined as a reduction from Baseline of = 50% in RBC-transfusion frequency during the prior 84-day interval) could continue to receive pomalidomide until loss of RBC-transfusion independence response or clinical benefit, or other criteria for treatment discontinuation applied.

Placebo comparator: Placebo - Participants received placebo taken by mouth once daily for at least 168 days unless there were unacceptable side effects or disease progression.

Participants who were RBC-transfusion independent or experienced clinical benefit could continue to receive placebo until loss of RBC- transfusion independence response or clinical benefit, or other criteria for treatment discontinuation applied.

Experimental: China Extension: Pomalidomide 0.5 mg - Participants received pomalidomide 0.5 mg/day by mouth for at least 168 days unless there were unacceptable side effects, disease progression, or they received a RBC-transfusion.

Participants who experienced anemia response could continue treatment until the response was lost or other criteria for treatment discontinuation applied.


Treatment: Drugs: Pomalidomide 0.5 mg
Pomalidomide 0.5 mg capsule taken by mouth once daily. Immunomodulatory agent with demonstrated efficacy in the treatment of subjects with RBC-transfusion-dependence associated with MNP-associated myelofibrosis.

Treatment: Drugs: Placebo
Placebo Comparator to active drug; Placebo capsule taken by mouth once daily

Treatment: Drugs: Pomalidomide
Pomalidomide 0.5 mg capsule taken by mouth once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Achieved RBC-Transfusion Independence
Timepoint [1] 0 0
168 days
Primary outcome [2] 0 0
China Extension: Number of Participants Achieving a Hemoglobin Increase of = 15 g/L Compared to Baseline for = 84 Consecutive Days
Timepoint [2] 0 0
From the first dose of study drug until treatment discontinuation; median treatment duration was 24.0 weeks.
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
From first dose of study drug up to end of study; median follow-up time was 19.1 months in the pomalidomide 0.5 mg arm and 17.6 months in the placebo arm.
Secondary outcome [2] 0 0
Duration of RBC-Transfusion Independence
Timepoint [2] 0 0
From first dose of study drug up to 28 days after last dose, as of the data cut-off date of 16 Jan 2013; median treatment duration was 23.6 weeks in the pomalidomide arm and 23.9 weeks in the placebo arm.
Secondary outcome [3] 0 0
Time to RBC-Transfusion Independence
Timepoint [3] 0 0
168 days
Secondary outcome [4] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Timepoint [4] 0 0
From the first dose of study drug until 28 days after last dose; median treatment duration was 23.7 weeks in the pomalidomide arm, 23.9 weeks in the placebo arm, and 24.0 weeks in the China extension pomalidomide arm.
Secondary outcome [5] 0 0
Healthcare Resource Utilization
Timepoint [5] 0 0
From first dose of study drug up to 28 days after last dose, as of the data cut-off date of 16 Jan 2013; median treatment duration was 23.6 weeks in the pomalidomide arm and 23.9 weeks in the placebo arm.
Secondary outcome [6] 0 0
Change From Baseline in EuroQoL-5D (EQ-5D) Health Index Score
Timepoint [6] 0 0
Baseline and Days 85 and 169
Secondary outcome [7] 0 0
Change From Baseline in EuroQoL-5D (EQ-5D) Visual Analog Scale
Timepoint [7] 0 0
Baseline and Days 85 and 169
Secondary outcome [8] 0 0
Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Total Score
Timepoint [8] 0 0
Baseline and Days 85 and 169

Eligibility
Key inclusion criteria
* Age = 18 years
* Myeloproliferative-neoplasm (MPN)-associated myelofibrosis
* RBC-transfusion-dependence (global study):

* Average RBC-transfusion frequency = 2 units/28 days over at least the 84 days immediately prior to randomization. There must be no interval > 42 days without = 1 RBC-transfusion.
* Only RBC-transfusions given when the hemoglobin = 90 g/L³ are scored in

determining eligibility.

* RBC-transfusions due to bleeding are not scored in determining eligibility.
* RBC-transfusions due to chemotherapy-induced anemia are not scored in determining eligibility.

* Severe anemia (China-specific extension):
* = 2 hemoglobin concentrations = 80 g/L for = 84 days immediately before the day of enrollment.
* No RBC-transfusion within 6 months prior to enrollment.

* Hemoglobin = 130 g/L at randomization (global study); = 80 g/L at enrollment in the China-specific extension.
* Bone marrow biopsy within 6 months (global study only).
* Inappropriate to receive blood cell or bone marrow allotransplant, erythropoietin and androgenic steroids
* Eastern Cooperative Oncology Group (ECOG) performance status = 2.
* Agree to follow pregnancy precautions as required by the protocol.
* Agree to receive counseling related to teratogenic and other risks of pomalidomide.
* Agree not to donate blood or semen.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior blood cell or bone marrow allotransplant.
* Use of drugs to treat MPN-associated myelofibrosis = 30 days before starting study drug.
* Treatment with erythropoietin or androgenic steroids = 84 days before starting study drug.
* Anemia due to reasons other than MPN-associated myelofibrosis.
* Pregnant or lactating females.
* More than 10% blasts by bone marrow examination or more than 10% blasts in blood in consecutive measurements spanning at least 8 weeks
* Prior history of malignancies,other than the disease being studied, unless the subject has been free of the malignancy for = 5 years with the following exceptions:

* Carcinoma in situ of the cervix
* Carcinoma in situ of the breast
* Incidental histologic finding of prostate cancer (T 1a or T 1b using TNM [tumor, nodes, metastasis] clinical staging system)
* Human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections.
* Prior treatment with pomalidomide.
* Allergic reaction or rash after treatment with thalidomide or lenalidomide
* Any of the following laboratory abnormalities:

* Neutrophils < 0.5x10^9 /L
* Platelets < 25 x 10^9 /L
* Estimated glomerular filtration rate (kidney function) < 30 mL/min/1.73 m²
* Aspartate aminotransferase (AST) and alanine transaminase (ALT) > 3.0 x upper limit of normal (ULN)
* Total bilirubin = 4 x ULN;
* Uncontrolled hyperthyroidism or hypothyroidism.
* Deep venous thrombosis (DVT) or pulmonary embolus (PE) < 6 months before starting study drug
* Clinically-important heart disease within the past 6 months

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
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
8/09/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/05/2018
Sample size
Target
Accrual to date
Final
267
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Gosford Hospital - Gosford
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St. Leonards
Recruitment hospital [3] 0 0
Frankston Hospital - Frankston
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
2065 - St. Leonards
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
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Florida
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United States of America
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Illinois
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Michigan
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Minnesota
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New York
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Ohio
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Pennsylvania
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South Dakota
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Texas
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Utah
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Washington
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Austria
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Graz
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Innsbruck
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Vienna
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Brugge
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Charleroi
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Leuven
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Ontario
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Canada
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Montreal,
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China
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Beijing
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China
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Jiangsu
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China
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China
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China
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Tianjin
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Lille
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Paris
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Pessac
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Toulouse
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Villejuif
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Hannover
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Leipzig
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Minden
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Ulm
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Bari
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Bergamo
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Napoli
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Orbassano
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Pavia
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Varese
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Japan
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Bunkyou-ku
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Japan
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Fukuoka City
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Japan
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Isehara City
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Kyoto City
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Shinjuku
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Amsterdam
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Rotterdam
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Utrecht
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Poland
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Rzeszow
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Szczecin
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Warsaw
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Moscow
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Spain
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Barcelona
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Majadahonda
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Salamanca
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Valencia
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Lund
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Stockholm
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United Kingdom
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Belfast
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Glasgow
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Headington
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London
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Newcastle upon Tyne
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Sheffield

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

Ethics approval
Ethics application status

Summary
Brief summary
The objective of this study is to determine whether pomalidomide is safe and effective in reversing red blood cell (RBC)-transfusion-dependence in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis (global study) and in reversing anemia in Chinese with MPN-associated myelofibrosis and severe anemia not receiving RBC-transfusions (China extension study only)
Trial website
https://clinicaltrials.gov/study/NCT01178281
Trial related presentations / publications
Tefferi A, Al-Ali HK, Barosi G, Devos T, Gisslinger H, Jiang Q, Kiladjian JJ, Mesa R, Passamonti F, McMullin MF, Ribrag V, Schiller G, Vannucchi AM, Zhou D, Reiser D, Zhong J, Gale RP. A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence. Leukemia. 2017 Apr;31(4):896-902. doi: 10.1038/leu.2016.300. Epub 2016 Oct 24. Erratum In: Leukemia. 2017 May;31(5):1252. doi: 10.1038/leu.2017.2.
Begna KH, Pardanani A, Mesa R, Litzow MR, Hogan WJ, Hanson CA, Tefferi A. Long-term outcome of pomalidomide therapy in myelofibrosis. Am J Hematol. 2012 Jan;87(1):66-8. doi: 10.1002/ajh.22233. Epub 2011 Nov 12.
Public notes

Contacts
Principal investigator
Name 0 0
Robert Peter P Gale, MD, Ph.D.
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01178281