Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Dakota
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Utah
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Austria
State/province [14] 0 0
Graz
Country [15] 0 0
Austria
State/province [15] 0 0
Innsbruck
Country [16] 0 0
Austria
State/province [16] 0 0
Vienna
Country [17] 0 0
Belgium
State/province [17] 0 0
Brugge
Country [18] 0 0
Belgium
State/province [18] 0 0
Charleroi
Country [19] 0 0
Belgium
State/province [19] 0 0
Leuven
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Canada
State/province [21] 0 0
British Columbia
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
Canada
State/province [23] 0 0
Montreal,
Country [24] 0 0
China
State/province [24] 0 0
Beijing
Country [25] 0 0
China
State/province [25] 0 0
Jiangsu
Country [26] 0 0
China
State/province [26] 0 0
Shanghai
Country [27] 0 0
China
State/province [27] 0 0
Sichuan
Country [28] 0 0
China
State/province [28] 0 0
Tianjin
Country [29] 0 0
France
State/province [29] 0 0
La Tronche
Country [30] 0 0
France
State/province [30] 0 0
Lille
Country [31] 0 0
France
State/province [31] 0 0
Limoges
Country [32] 0 0
France
State/province [32] 0 0
Paris
Country [33] 0 0
France
State/province [33] 0 0
Pessac
Country [34] 0 0
France
State/province [34] 0 0
Strasbourg
Country [35] 0 0
France
State/province [35] 0 0
Toulouse
Country [36] 0 0
France
State/province [36] 0 0
Villejuif
Country [37] 0 0
Germany
State/province [37] 0 0
Aachen
Country [38] 0 0
Germany
State/province [38] 0 0
Hannover
Country [39] 0 0
Germany
State/province [39] 0 0
Leipzig
Country [40] 0 0
Germany
State/province [40] 0 0
Minden
Country [41] 0 0
Germany
State/province [41] 0 0
Ulm
Country [42] 0 0
Italy
State/province [42] 0 0
Bari
Country [43] 0 0
Italy
State/province [43] 0 0
Bergamo
Country [44] 0 0
Italy
State/province [44] 0 0
Firenze
Country [45] 0 0
Italy
State/province [45] 0 0
Napoli
Country [46] 0 0
Italy
State/province [46] 0 0
Orbassano
Country [47] 0 0
Italy
State/province [47] 0 0
Pavia
Country [48] 0 0
Italy
State/province [48] 0 0
Varese
Country [49] 0 0
Japan
State/province [49] 0 0
Bunkyou-ku
Country [50] 0 0
Japan
State/province [50] 0 0
Fukuoka City
Country [51] 0 0
Japan
State/province [51] 0 0
Isehara City
Country [52] 0 0
Japan
State/province [52] 0 0
Kyoto City
Country [53] 0 0
Japan
State/province [53] 0 0
Nagasaki City
Country [54] 0 0
Japan
State/province [54] 0 0
Shinjuku
Country [55] 0 0
Netherlands
State/province [55] 0 0
Amsterdam
Country [56] 0 0
Netherlands
State/province [56] 0 0
Rotterdam
Country [57] 0 0
Netherlands
State/province [57] 0 0
Utrecht
Country [58] 0 0
Poland
State/province [58] 0 0
Rzeszow
Country [59] 0 0
Poland
State/province [59] 0 0
Szczecin
Country [60] 0 0
Poland
State/province [60] 0 0
Warsaw
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Moscow
Country [62] 0 0
Russian Federation
State/province [62] 0 0
Saint-Petersburg
Country [63] 0 0
Spain
State/province [63] 0 0
Barcelona
Country [64] 0 0
Spain
State/province [64] 0 0
Majadahonda
Country [65] 0 0
Spain
State/province [65] 0 0
Salamanca
Country [66] 0 0
Spain
State/province [66] 0 0
Valencia
Country [67] 0 0
Sweden
State/province [67] 0 0
Lund
Country [68] 0 0
Sweden
State/province [68] 0 0
Stockholm
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Belfast
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Glasgow
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Headington
Country [72] 0 0
United Kingdom
State/province [72] 0 0
London
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Newcastle upon Tyne
Country [74] 0 0
United Kingdom
State/province [74] 0 0
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/ct2/show/NCT01178281
Trial related presentations / publications
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/ct2/show/NCT01178281