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

NCT01178281 | Completed Phase 3 Results DMC

• 2 other identifiers: CC-4047-MF-0022010-018965-42
• Study Type: interventional
• Target: 267
• Locations: 15 countries
• Sites: 84

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)

Conditions

Primary Myelofibrosis; MPN-associated Myelofibrosis

Keywords

Myelofibrosis; Post-polycythemia vera myelofibrosis; Post-essential thrombocythemia myelofibrosis; RBC-transfusion-dependence; Primary Myelofibrosis

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Achieved RBC-Transfusion Independence

  RBC-transfusion independence was defined as the absence of RBC transfusions for any consecutive 84-day interval.

  168 days

• China Extension: Number of Participants Achieving a Hemoglobin Increase of ≥ 15 g/L Compared to Baseline for ≥ 84 Consecutive Days

  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.

  From the first dose of study drug until treatment discontinuation; median treatment duration was 24.0 weeks.

Secondary Outcomes (8)

• Overall Survival

  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.

• Duration of RBC-Transfusion Independence

  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.

• Time to RBC-Transfusion Independence

  168 days

• Number of Participants With Treatment-emergent Adverse Events (TEAE)

  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.

• Healthcare Resource Utilization

  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.

Study Arms (3)

Pomalidomide 0.5 mg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

China Extension: Pomalidomide 0.5 mg

EXPERIMENTAL

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.

Drug: Pomalidomide

Interventions

Pomalidomide 0.5 mg 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.

Also known as: CC-4047; Pomalyst; Imnovid

Pomalidomide 0.5 mg

Placebo DRUG

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

Placebo

Pomalidomide DRUG

Pomalidomide 0.5 mg capsule taken by mouth once daily.

Also known as: CC-4047, Pomalyst, Imnovid

China Extension: Pomalidomide 0.5 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (87)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

UCLA School of Medicine

Los Angeles, California, 90095, United States

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Mount Sinai School of Medicine Brookdale University Hospital

Brooklyn, New York, 11212, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Ruttenberg Treatment Center

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Medicine Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Avera Hematology and Transplant

Sioux Falls, South Dakota, 57105, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Frankston Hospital

Frankston, Victoria, 3199, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Medizinische Universitatklinik Graz

Graz, A-8036, Austria

Location

Medizinische Universitat Innsbruck

Innsbruck, A-6020, Austria

Location

Medizinische Universitat Wien

Vienna, A-1190, Austria

Location

Algemeen Ziekenhuis Sint-Jan

Bruges, 8000, Belgium

Location

Grand Hopital de Charleroi

Charleroi, 6000, Belgium

Location

Universitaire Ziekenhuis Leuven Gathuisberg

Leuven, 3000, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, T6G lz2, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier de L'Universite de Montreal

Montreal, Canada

Location

Peking University People's Hospital

Beijing, 100044, China

Location

Peking Union Medical College Hospital

Beijing, 100730, China

Location

Jiangsu Province Hospital

Jiangsu, 210029, China

Location

Shanghai Ruijin Hospital

Shanghai, 200025, China

Location

West China Hospital, Sichuan University

Sichuan, 610041, China

Location

Blood Disease Hospital Chinese Academy of Medical Sciences

Tianjin, 300041, China

Location

Hopital Albert Michallon

La Tronche, 38043, France

Location

Hopital Saint Vincent de Paul

Lille, 59020, France

Location

CHU Dupuytren

Limoges, 87042, France

Location

Hopital Saint-Louis

Paris, 75475, France

Location

CHRU - Hopital du Haut Leveque

Pessac, 33604, France

Location

Hopitaux Universitaires de Strasbourg, CHU Haute-Pierre

Strasbourg, 67098, France

Location

Hopital Purpan

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitatsklinikum Aachen

Aachen, 52074, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

Johannes Wesling Klinikum Minden

Minden, 32429, Germany

Location

Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari

Bari, 70124, Italy

Location

Ospedali Riuniti di Bergamo

Bergamo, 24128, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Azienda Ospedaliera Universitaria Federico II di Napoli

Napoli, 80131, Italy

Location

Azienda Ospedaliera San Luigi Gonzaga

Orbassano, 10043, Italy

Location

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

Pavia, 27100, Italy

Location

IRCCS Fondazione Policlinico San Matteo, Universita di Pavia, Ematologia

Pavia, 27100, Italy

Location

Ospedale di Circolo e Fondazione Macchi Varese

Varese, 21100, Italy

Location

Juntendo University Hospital

Bunkyou-ku, 113-8431, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Tokai University Hospital

Isehara, 259-1193, Japan

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

Location

Tokyo Medical University Hospital

Shinjuku, 160-0023, Japan

Location

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Erasmus Medish Centrum

Rotterdam, 3015 CE, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Wojewodzki Szpital Specjalistyczny im. F.Chopina

Rzeszów, 35-055, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 1 PAM

Szczecin, 71-242, Poland

Location

Centralny Szpital Kliniczny MSWiA

Warsaw, 02-507, Poland

Location

Russian Scientific Haematology Centre

Moscow, 125167, Russia

Location

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

Saint Petersburg, 191024, Russia

Location

State Pavlov Medical University

Saint Petersburg, 196022, Russia

Location

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

Saint Petersburg, 197341, Russia

Location

Hospital Clinic I Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Puerta De Hierro Majadahonda

Majadahonda, 28222, Spain

Location

Hospital Clinico de Salamanca

Salamanca, 37007, Spain

Location

Hospital Clinico de Valencia

Valencia, 46010, Spain

Location

Skane University Hospital

Lund, 22185, Sweden

Location

Karolinska University Hospital Huddinge

Stockholm, 14185, Sweden

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Beatson Oncology Centre

Glasgow, G12 0YN, United Kingdom

Location

John Radcliffe Hospital NHS Trust

Headington, OX3 9DU, United Kingdom

Location

St. Thomas Hospital

London, SE1 9RT, United Kingdom

Location

Hammersmith Hospital

London, W12 ONN, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 27773929 DERIVED

• 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.

  PMID: 22081489 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

pomalidomide

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Anne McClain
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Robert Peter P Gale, MD, Ph.D.

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: August 10, 2010
• Study Start: September 8, 2010
• Primary Completion: January 1, 2013
• Study Completion: May 15, 2018
• Last Updated: July 17, 2019
• Results First Posted: March 14, 2014

Record last verified: 2019-06

Locations

ES (4); DE (5); IT (8); CA (4); AU (4); PL (3); RU (4); FR (8); US (17); BE (3); CN (6); NL (3); JP (6); GB (7); SE (2)