Study of Pomalidomide in Persons With Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence

NCT ID: NCT01178281

Last Updated: 2019-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 267 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-08
• Study Completion Date: 2018-05-15

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.

Conditions

Primary Myelofibrosis; MPN-associated Myelofibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Pomalidomide 0.5 mg

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Pomalidomide

Intervention Type: DRUG

Pomalidomide 0.5 mg capsule taken by mouth once daily.

Interventions

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Pomalidomide

Pomalidomide 0.5 mg capsule taken by mouth once daily.

Intervention Type: DRUG

Other Intervention Names

CC-4047; Pomalyst; Imnovid; CC-4047; Pomalyst; Imnovid

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Peter P Gale, MD, Ph.D.

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

Mayo Clinic

Scottsdale, Arizona, United States

UCLA School of Medicine

Los Angeles, California, United States

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Mayo Clinic

Jacksonville, Florida, United States

University of Illinois at Chicago

Chicago, Illinois, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Mount Sinai School of Medicine Brookdale University Hospital

Brooklyn, New York, United States

Weill Medical College of Cornell University

New York, New York, United States

Ruttenberg Treatment Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Medicine Taussig Cancer Institute

Cleveland, Ohio, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Avera Hematology and Transplant

Sioux Falls, South Dakota, United States

MD Anderson Cancer Center

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Gosford Hospital

Gosford, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Frankston Hospital

Frankston, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Medizinische Universitatklinik Graz

Graz, , Austria

Medizinische Universitat Innsbruck

Innsbruck, , Austria

Medizinische Universitat Wien

Vienna, , Austria

Algemeen Ziekenhuis Sint-Jan

Bruges, , Belgium

Grand Hopital de Charleroi

Charleroi, , Belgium

Universitaire Ziekenhuis Leuven Gathuisberg

Leuven, , Belgium

Cross Cancer Institute

Edmonton, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Centre Hospitalier de L'Universite de Montreal

Montreal, , Canada

Peking University People's Hospital

Beijing, , China

Peking Union Medical College Hospital

Beijing, , China

Jiangsu Province Hospital

Jiangsu, , China

Shanghai Ruijin Hospital

Shanghai, , China

West China Hospital, Sichuan University

Sichuan, , China

Blood Disease Hospital Chinese Academy of Medical Sciences

Tianjin, , China

Hopital Albert Michallon

La Tronche, , France

Hopital Saint Vincent de Paul

Lille, , France

CHU Dupuytren

Limoges, , France

Hopital Saint-Louis

Paris, , France

CHRU - Hopital du Haut Leveque

Pessac, , France

Hopitaux Universitaires de Strasbourg, CHU Haute-Pierre

Strasbourg, , France

Hopital Purpan

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Universitatsklinikum Aachen

Aachen, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitatsklinikum Leipzig

Leipzig, , Germany

Johannes Wesling Klinikum Minden

Minden, , Germany

Universitatsklinikum Ulm

Ulm, , Germany

Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari

Bari, , Italy

Ospedali Riuniti di Bergamo

Bergamo, , Italy

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

Azienda Ospedaliera Universitaria Federico II di Napoli

Napoli, , Italy

Azienda Ospedaliera San Luigi Gonzaga

Orbassano, , Italy

IRCCS Fondazione Policlinico San Matteo, Universita di Pavia, Centro per lo Studio della Mielofibrosi

Pavia, , Italy

IRCCS Fondazione Policlinico San Matteo, Universita di Pavia, Ematologia

Pavia, , Italy

Ospedale di Circolo e Fondazione Macchi Varese

Varese, , Italy

Juntendo University Hospital

Bunkyou-ku, , Japan

Kyushu University Hospital

Fukuoka, , Japan

Tokai University Hospital

Isehara, , Japan

Kyoto University Hospital

Kyoto, , Japan

Nagasaki University Hospital

Nagasaki, , Japan

Tokyo Medical University Hospital

Shinjuku, , Japan

VU University Medical Center

Amsterdam, , Netherlands

Erasmus Medish Centrum

Rotterdam, , Netherlands

University Medical Center Utrecht

Utrecht, , Netherlands

Wojewodzki Szpital Specjalistyczny im. F.Chopina

Rzeszów, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 PAM

Szczecin, , Poland

Centralny Szpital Kliniczny MSWiA

Warsaw, , Poland

Russian Scientific Haematology Centre

Moscow, , Russia

Federal State Institution Russian Scientific-research Institute of Hematology and Transfusiology of Federal Medical-Biological Agency of Russia

Saint Petersburg, , Russia

State Pavlov Medical University

Saint Petersburg, , Russia

Federal State Institution "Federal Centre of Heart, Blood and Endocrinology of Rosmedtechnologies named after V.A. Almazov"

Saint Petersburg, , Russia

Hospital Clinic I Provincial de Barcelona

Barcelona, , Spain

Hospital Universitario Puerta De Hierro Majadahonda

Majadahonda, , Spain

Hospital Clinico de Salamanca

Salamanca, , Spain

Hospital Clinico de Valencia

Valencia, , Spain

Skane University Hospital

Lund, , Sweden

Karolinska University Hospital Huddinge

Stockholm, , Sweden

Belfast City Hospital

Belfast, , United Kingdom

Beatson Oncology Centre

Glasgow, , United Kingdom

John Radcliffe Hospital NHS Trust

Headington, , United Kingdom

St. Thomas Hospital

London, , United Kingdom

Hammersmith Hospital

London, , United Kingdom

Freeman Hospital

Newcastle upon Tyne, , United Kingdom

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; China; France; Germany; Italy; Japan; Netherlands; Poland; Russia; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 27773929 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22081489 (View on PubMed)

Other Identifiers

2010-018965-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-4047-MF-002

Identifier Type: -

Identifier Source: org_study_id