Study of Pomalidomide in Persons With Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence (RESUME)
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|ClinicalTrials.gov Identifier: NCT01178281|
Recruitment Status : Completed
First Posted : August 10, 2010
Results First Posted : March 14, 2014
Last Update Posted : July 17, 2019
|Condition or disease||Intervention/treatment||Phase|
|Primary Myelofibrosis MPN-associated Myelofibrosis||Drug: Pomalidomide 0.5 mg Drug: Placebo Drug: Pomalidomide||Phase 3|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||267 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official 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|
|Actual Study Start Date :||September 8, 2010|
|Actual Primary Completion Date :||January 1, 2013|
|Actual Study Completion Date :||May 15, 2018|
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.
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
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.
Placebo Comparator to active drug; Placebo capsule taken by mouth once daily
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.
Pomalidomide 0.5 mg capsule taken by mouth once daily.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01178281
|Study Director:||Robert Peter P Gale, MD, Ph.D.||Celgene Corporation|