Phase-3 Double-Blind, Placebo-Controlled Study of Pomalidomide in Persons With Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence Myelofibrosis and RBC-Transfusion-Dependence (RESUME)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01178281
First received: July 15, 2010
Last updated: January 31, 2014
Last verified: January 2014
Results First Received: January 31, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Primary Myelofibrosis
Interventions: Drug: Pomalidomide 0.5 mg
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 252 participants were randomized into the double-blind phase of the study across 15 countries. They were randomized 2:1 in a blinded manner to receive pomalidomide 0.5 mg/day or matching placebo capsule/day.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants had myeloproliferative neoplasm (MPN)-associated myelofibrosis defined as primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis and were red blood cell (RBC) transfusion-dependent having an average RBC-transfusion-frequency of ≥2 units of RBC every 28 days over at least 84 days.

Reporting Groups
  Description
Pomalidomide 0.5 mg (Oral Capsule) Pomalidomide 0.5 mg by mouth daily Days 1 through Day 168
Placebo (Oral Capsule) One matching capsule by mouth daily Days 1 through Day 168

Participant Flow:   Overall Study
    Pomalidomide 0.5 mg (Oral Capsule)     Placebo (Oral Capsule)  
STARTED     168 [1]   84 [1]
COMPLETED     19 [2]   7 [2]
NOT COMPLETED     149     77  
Physician Decision                 4                 3  
Loss of Clinical Benefit                 5                 7  
Lack of Efficacy                 60                 38  
Non-compliance to study drug                 1                 0  
Disease Progression                 18                 6  
Death                 4                 5  
Withdrawal by Subject                 18                 7  
Adverse Event                 39                 9  
Prohibited Medications                 0                 2  
[1] Intent to Treat Population (ITT)
[2] Participants remain on treatment



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to Treat (ITT) population included all randomized participants

Reporting Groups
  Description
Pomalidomide 0.5 mg (Oral Capsule) Pomalidomide 0.5 mg by mouth daily Days 1 through Day 168
Placebo (Oral Capsule) Matching oral placebo Days 1 through Day 168
Total Total of all reporting groups

Baseline Measures
    Pomalidomide 0.5 mg (Oral Capsule)     Placebo (Oral Capsule)     Total  
Number of Participants  
[units: participants]
  168     84     252  
Age  
[units: Years]
Mean ± Standard Deviation
  68.0  ± 8.89     68.6  ± 8.16     68.2  ± 8.64  
Gender  
[units: participants]
     
Female     41     28     69  
Male     127     56     183  
ECOG Performance Status [1]
[units: participants]
     
0 = (Fully Active)     53     22     75  
1 = (Restrictive but ambulatory)     85     47     132  
2 = (Ambulatory but unable to work)     30     15     45  
3 = (Limited self care)     0     0     0  
4 = (Completely Disabled)     0     0     0  
Baseline RBC Transfusion Burden (units/28days) [2]
[units: units per 28 days]
Mean ± Standard Deviation
  3.5  ± 1.84     3.5  ± 1.76     3.5  ± 1.81  
Disease Sub-type: Primary Myelofibrosis (PMF) [3]
[units: Participants]
     
Yes     127     65     192  
No     41     19     60  
Disease sub-type: Post-polycythemia Vera Myelofibrosis [4]
[units: Participants]
     
Yes     17     8     25  
No     151     76     227  
Disease sub-type: Post-Essential Thrombocythemia Myelofibrosis [5]
[units: participants]
     
Yes     23     11     34  
No     145     73     218  
[1]

ECOG-Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis.

0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)

[2] Defined as the average number of RBC-transfusion-units per 28 days over the 84 days immediately prior to randomization.
[3] PMF criteria: 1. Presence of megakaryocyte proliferation and atypiaa, accompanied by either reticulin or collagen fibrosis, or, in the absence of significant reticulin fibrosis, the megakaryocyte changes must be accompanied by an increased bone marrow cellularity characterized by granulocytic proliferation and decreased erythropoiesis 2. Not meeting World Health Organization (WHO) criteria for polycythemia vera, BCR-ABL1–positive chronic myelogenous leukemia, myelodysplastic syndrome, or other myeloid disorders. 3. Demonstration of JAK2 V617F or other clonal marker (eg, MPLW515K/L)
[4] The polycythemia Vera (pPV) major and minor critiera: 1. Hemoglobin >18.5 g/dL in men, >16.5 g/dL in women or other evidence of increased red cell volume. 2. Presence of JAK2 V617F or other functionally similar mutation such as JAK2 exon 12 mutation. 3. Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation. 4. Serum erythropoietin level below the reference range for normal. 5. Endogenous erythroid colony formation in vitro.
[5] Post-Essential Thrombocytemia Myelofibrosis. (pET) include all 4 criteria: 1. Platelet count ≥450 x 10^9/L. 2. Bone marrow biopsy specimen showing proliferation of the megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes. No increase or left-shift of neutrophil granulopoiesis or erythropoiesis. 3. Not meeting WHO criteria for PV, primary myelofibrosis, BCR-ABL1–positive CML, or myelodysplastic syndrome, or other myeloid neoplasm. 4. Demonstration of JAK2 V617F or other clonal marker, or in the absence of JAK2 V617F, no evidence of reactive thrombocytosis.



  Outcome Measures

1.  Primary:   Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence   [ Time Frame: 168 days ]

2.  Secondary:   Duration of RBC-transfusion Independence   [ Time Frame: Up to 2.5 years ]
Results not yet posted.   Anticipated Posting Date:   08/2018   Safety Issue:   No

3.  Secondary:   Time to Becoming RBC-transfusion-independent   [ Time Frame: Up to 2.5 years ]
Results not yet posted.   Anticipated Posting Date:   08/2018   Safety Issue:   No

4.  Secondary:   Healthcare Resource Utilization   [ Time Frame: Every 28 days ]
Results not yet posted.   Anticipated Posting Date:   08/2018   Safety Issue:   No

5.  Secondary:   Euro QOL 5 Dimension Questionaire   [ Time Frame: Up to treatment discontinuation ]
Results not yet posted.   Anticipated Posting Date:   08/2018   Safety Issue:   No

6.  Secondary:   FACT-Anemia Quality of Life Questionaire   [ Time Frame: Up to treatment discontinuation ]
Results not yet posted.   Anticipated Posting Date:   08/2018   Safety Issue:   No

7.  Secondary:   Frequency of Adverse Events   [ Time Frame: Up to 2.5 years ]
Results not yet posted.   Anticipated Posting Date:   08/2018   Safety Issue:   Yes

8.  Secondary:   Overall Survival   [ Time Frame: Up to 2.5 years ]
Results not yet posted.   Anticipated Posting Date:   08/2018   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Anne McClain
Organization: Celgene Corporation
phone: 1-888-260-1599
e-mail: clinicaltrialdisclosure@celgene.com


No publications provided by Celgene Corporation

Publications automatically indexed to this study:

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01178281     History of Changes
Other Study ID Numbers: CC-4047-MF-002, 2010-018965-42
Study First Received: July 15, 2010
Results First Received: January 31, 2014
Last Updated: January 31, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
China: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
Netherlands: Medicines Evaluation Board (MEB)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration