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Trial record 1 of 1 for:    Study of Pomalidomide in Persons with Myelofibrosis
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Study of Pomalidomide in Persons With Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence (RESUME)

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01178281
Recruitment Status : Completed
First Posted : August 10, 2010
Results First Posted : March 14, 2014
Last Update Posted : July 17, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE July 15, 2010
First Posted Date  ICMJE August 10, 2010
Results First Submitted Date  ICMJE January 31, 2014
Results First Posted Date  ICMJE March 14, 2014
Last Update Posted Date July 17, 2019
Actual Study Start Date  ICMJE September 8, 2010
Actual Primary Completion Date January 1, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
  • Percentage of Participants Who Achieved RBC-Transfusion Independence [ Time Frame: 168 days ]
    RBC-transfusion independence was defined as the absence of RBC transfusions for any consecutive 84-day interval.
  • China Extension: Number of Participants Achieving a Hemoglobin Increase of ≥ 15 g/L Compared to Baseline for ≥ 84 Consecutive Days [ Time Frame: From the first dose of study drug until treatment discontinuation; median treatment duration was 24.0 weeks. ]
    A response in the China extension study was defined as an increase in hemoglobin ≥ 15 g/L above baseline value (in the absence of RBC transfusion) for ≥ 84 consecutive days.
Original Primary Outcome Measures  ICMJE
 (submitted: August 9, 2010)
Proportion of subjects achieving RBC-transfusion-independence [ Time Frame: 6 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
  • Overall Survival [ Time Frame: 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. ]
    The time from randomization to the death or to the latest date when participants are known to be alive. Overall survival was analyzed using Kaplan-Meier method; participants who were alive or lost to follow-up were censored at the latest date they were known to be alive.
  • Duration of RBC-Transfusion Independence [ Time Frame: 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. ]
    The duration of RBC-transfusion independence is the time from the date at which the first RBC-transfusion independence started to the date of another RBC-transfusion given at least 84 days after the time the transfusion independence started. The duration of the RBC-transfusion independence was analyzed using the Kaplan-Meier method. Data were censored at the end of the treatment phase for participants who had not received another RBC-transfusion after the start of transfusion independence by the end of treatment phase.
  • Time to RBC-Transfusion Independence [ Time Frame: 168 days ]
    Time to response was measured from first dose of study drug to the start of the first response. The start date of the response was defined as one day after the last date of an RBC-transfusion for participants who received a RBC-transfusion after the first dose, and as the date of the first dose of study drug for participants who received no RBC-transfusions during the 84 days after the first dose of study drug.
  • Number of Participants With Treatment-emergent Adverse Events (TEAE) [ Time Frame: 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. ]
    A TEAE is an adverse event (AE) that starts on or after the first dose of study drug. The severity of each AE was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE),Version 4.0 and according to the following scale: Grade 1 = Mild (transient or mild discomfort; no limitation in activity; no medical intervention/therapy required); Grade 2 = Moderate (mild to moderate limitation in activity, some assistance may be needed; minimal medical intervention/therapy required); Grade 3 = Severe (marked limitation in activity, assistance usually required; medical intervention/therapy required, hospitalization possible); Grade 4 = Life-threatening (extreme limitation in activity, significant assistance or medical intervention/therapy required, hospitalization or hospice care probable); Grade 5 = Death Drug-related (related) AEs are those suspected by the Investigator as being related to administration of study drug
  • Healthcare Resource Utilization [ Time Frame: 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. ]
  • Change From Baseline in EuroQoL-5D (EQ-5D) Health Index Score [ Time Frame: Baseline and Days 85 and 169 ]
    EQ-5D is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D includes 2 components: the EQ-5D health state profile (descriptive system) and the EQ-5D visual analog scale (VAS). For the health state profile participants rate their perceived health state today on 5 dimensions: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression on a Likert-type scale from 1 to 3, where 1 = "no problems," 2 = "some problems," and 3 = "extreme problems." The EQ-5D Health Utility Index (HUI) was generated from the five health state domain scores, and ranges from -0.594 (worst) and 1 (best) imaginable health state, with -0.594 representing an "unconscious" health state.
  • Change From Baseline in EuroQoL-5D (EQ-5D) Visual Analog Scale [ Time Frame: Baseline and Days 85 and 169 ]
    EQ-5D is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D includes 2 components: the EQ-5D health state profile (descriptive system) and the EQ-5D visual analog scale (VAS). On the VAS the participant rates his/her health state on a line from 0 (worst imaginable health) to 100 (best imaginable health).
  • Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Total Score [ Time Frame: Baseline and Days 85 and 169 ]
    The FACT-An is a 47-item, cancer-specific questionnaire consisting of a core 27-item general questionnaire measuring the four general domains of QoL (physical, social/family, emotional and functional well-being), and an additional 20-item anemia questionnaire (FACT-An Anemia subscale) that measures 13 fatigue-associated items (FACT-F Fatigue subscale) and seven non-fatigue-related items. Each item is scored using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 4 = Very much). FACT-An total score is calculated by adding all the FACT-An subscales together. The total score ranges from 0-188 with higher scores representing better QOL.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2010)
  • Duration of RBC-transfusion Independence [ Time Frame: Up to 3.5 years ]
  • Time to becoming RBC-transfusion-independent - every 28 days [ Time Frame: 2 years ]
  • Healthcare resource utilization [ Time Frame: Every 28 days ]
  • EQ-5D Health Outcome Assessment [ Time Frame: Day 1, 85, 169 and treatment discontinuation ]
  • FACT-An Quality of Life (QoL) Assessment [ Time Frame: D1, D84 and every 84 days while on treatment and treatment discontinuation ]
  • Frequency of AE's [ Time Frame: up to 2 years ]
  • Survival - alive or dead [ Time Frame: 6 months, 2 years and 5 years after the last subject is randomized ]
    Survival - alive or dead at 6 months, 2 years and 5 years after the last subject is randomized
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pomalidomide in Persons With Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence
Official Title  ICMJE 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
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)
Detailed Description

The multicenter global study was conducted in 15 countries including Australia, Austria, Belgium, Canada, China, France, Germany, Italy, Japan, the Netherlands, Russia, Spain, Sweden, the United Kingdom, and the United States. The global study enrolled participants with myeloproliferative neoplasm (MPN)-associated myelofibrosis and RBC-transfusion-dependence. Participants were randomly assigned to receive pomalidomide or placebo in a blinded fashion.

In most countries participating in the global study, RBC-transfusions are typically given for a hemoglobin level <80-90 g/L. In China, RBC-transfusions are rarely given unless the hemoglobin level is <60 g/L. Consequently, few Chinese with MPN-associated myelofibrosis meet RBC-transfusion-dependence criteria of the global study. A China-specific extension was developed to test the ability of pomalidomide to improve severe anemia (defined as a hemoglobin < 80 g/L for ≥ 84 days in persons not receiving RBC-transfusions).

The China-specific extension study consisted of a single-arm, open-label study in adults with MPN-associated myelofibrosis and severe anemia not receiving RBC transfusions with the objective of describing the frequency of anemia response.

The Global (intent-to-treat [ITT] and safety) population in the main study and the China extension (ITT and safety) population are mutually exclusive.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Myelofibrosis
  • MPN-associated Myelofibrosis
Intervention  ICMJE
  • Drug: 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.
    Other Name: CC-4047; Pomalyst; Imnovid
  • Drug: Placebo
    Placebo Comparator to active drug; Placebo capsule taken by mouth once daily
  • Drug: Pomalidomide
    Pomalidomide 0.5 mg capsule taken by mouth once daily.
    Other Names:
    • CC-4047
    • Pomalyst
    • Imnovid
Study Arms  ICMJE
  • 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.

    Intervention: Drug: Pomalidomide 0.5 mg
  • 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.

    Intervention: Drug: Placebo
  • 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.

    Intervention: Drug: Pomalidomide
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 24, 2019)
267
Original Estimated Enrollment  ICMJE
 (submitted: August 9, 2010)
210
Actual Study Completion Date  ICMJE May 15, 2018
Actual Primary Completion Date January 1, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   China,   France,   Germany,   Italy,   Japan,   Netherlands,   Poland,   Russian Federation,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01178281
Other Study ID Numbers  ICMJE CC-4047-MF-002
2010-018965-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Robert Peter P Gale, MD, Ph.D. Celgene Corporation
PRS Account Celgene
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP