Evaluation of Safety of Pomalidomide in Combination With Dexamethasone (Low Dose) in Patients With Refractory or Relapsed and Refractory Multiple Myeloma

NCT01712789 | Completed Phase 3 Results DMC

• 2 other identifiers: CC-4047-MM-0102012-001888-78
• Study Type: interventional
• Target: 682
• Locations: 19 countries
• Sites: 97

Brief Summary

The primary purpose of the study is to evaluate the safety and efficacy and to generate PK and biomarker data for the combination of pomalidomide and low-dose dexamethasone in patients with refractory or relapsed and refractory multiple myeloma. The study consists of a Screening phase within 28 days prior to cycle 1 day 1, a Treatment phase and a Follow-up phase which starts within 28 days of discontinuation from study treatment, every 3 months for up to 5 years. In addition, the collection of steady-state PK data from a large population will enable robust population PK and assess Pomalidomide exposure response analyses. The exploratory objectives of the study are to investigate potential markers predictive of POM response or resistance and pharmacodynamic markers.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Relapsed Multiple Myeloma; Relapsed and refractory Multiple Myeloma; Pomalidomide; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events (TEAE)

  An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, regardless of etiology. Any worsening (i.e., any significant adverse change in the frequency or intensity of a pre- existing condition) was considered an AE. The severity of AEs were graded based on the symptoms according to version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs. A SAE = AE occurring at any dose that: * Results in death; * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect

  From the first dose of study treatment up to 28 days following the last dose of study treatment. The median duration of treatment with pomalidomide and LD-dex was 21.4 weeks.

Secondary Outcomes (9)

• Overall Response

  Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks

• Time to Response

  Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks

• Kaplan Meier Estimate of Duration of Response

  From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months

• Kaplan Meier Estimate of Progression Free Survival (PFS) According to the European Medicines Agency Guidelines

  From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months

• Kaplan Meier Estimate of Time to Progression

  From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months

Study Arms (1)

Pomalidomide plus Dexamethasone

EXPERIMENTAL

Pomalidomide 4mg by mouth (PO) daily days 1 through 21 of a 28 day cycle and dexamethasone 40mg/day PO for those ≤75 years of age or 20mg/day for those greater than 75 years of age on Days 1, 8, 15 and 22 of a 28 day cycle.

Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Pomalidomide DRUG

Oral Pomalidomide at the starting dose of 4 mg on Days 1-21 of a 28-day cycle

Pomalidomide plus Dexamethasone

Dexamethasone DRUG

Oral Low dose Dexamethasone at the starting dose of 40mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle.

Pomalidomide plus Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Patients ≥18 years old, who must understand and voluntarily sign an Informed Consent.
• Patients must have documented diagnosis of Multiple Myeloma and have measurable disease.
• Patients must have undergone prior treatment with ≥ 2 treatments lines, of anti-myeloma therapy.
• Patients must have either refractory or relapsed and refractory disease.
• Patients must have received at least 2 consecutive cycles of prior treatment that include lenalidomide and bortezomib, either alone or in combination regimens.
• Patients must have received adequate alkylator therapy

You may not qualify if:

• Prior history of malignancies, other than Multiple Myeloma.
• Previous therapy with Pomalidomide, hypersensitivity to thalidomide and lenalidomide or dexamethasone.
• Patients who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant.
• Patients who are planning for or who are eligible for stem cell transplant.
• Patients who received major surgery and any anti-myeloma drug therapy within the last 14 days of starting study treatment.
• Patients with a current disease that can interfere with protocol procedures or study treatment.
• Patients unable or unwilling to undergo antithrombotic prophylactic treatment.
• Pregnant or breastfeeding females.

Sponsors & Collaborators

• Celgene: lead

Study Sites (112)

Medical University of Graz

Graz, A-8036, Austria

Location

Medizinische Universitat Innsbruck

Innsbruck, 6020, Austria

Location

Wilhelminenspital Vienna

Vienna, 1160, Austria

Location

Medical University of Vienna

Vienna, A-1090, Austria

Location

AZ St-Jan Brugge Oostende AV

Bruges, 8000, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

VUB Vrije Universiteit Brussel

Brussels, 1090, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Centre Hospitalier Universitaire de Liege

Liège, 4000, Belgium

Location

CHU Mont -Godinne

Yvoir, 5530, Belgium

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Odense University Hospital

Odense, DK-5000, Denmark

Location

Vejle Hospital

Vejle, 7100, Denmark

Location

Tartu University Hospital Clinic

Tartu, 51014, Estonia

Location

Helsingin yliopistollinen keskussairaala

Helsinki, FI-00290, Finland

Location

Turku University Hospital

Turku, 20521, Finland

Location

Centre Hospitalier de la cote basque

Bayonne, 64109, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Hopital A. Michallon

La Tronche, 38700, France

Location

CHRU Claude Huriez

Lille, 59037, France

Location

Institut Paoli Calmette Hematologie

Marseille, 13273, France

Location

CHU Hotel Dieu

Nantes, 44093, France

Location

Hopital Saint Antoine

Paris, 75012, France

Location

Service Hemato-Immunologie Hopital St Louis

Paris, 75475, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU de Reims

Reims, 51092, France

Location

Hematologie - CHU Purpan

Toulouse, 31059, France

Location

CHRU Hopital Bretonneau

Tours, 37044, France

Location

CHU Nancy Hematology

Vandœuvre-lès-Nancy, 54511, France

Location

Charite, Campus Benjamin Franklin Universitatsmedizin Berlin

Berlin, 12200, Germany

Location

Klinikum Chemnitz

Chemnitz, D-09113, Germany

Location

Klinikum der Universitat zu Koln

Cologne, 50937, Germany

Location

Universitatsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Universitatsklinkikum DusseldorfKlinik fur Hamatologie, Onkologie und klin. Immunoligie

Düsseldorf, D-40225, Germany

Location

Universitatsklinikum Essen-

Essen, 45122, Germany

Location

Universitatsklinikum Freiburg Medizinische Klinik und Poliklinik

Freiburg im Breisgau, D-79106, Germany

Location

Abt Haematologie - Onkologie / Allg. Krankenhaus Altona

Hamburg, D-22763, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitatsklinikum Jena

Jena, O7740, Germany

Location

University of Schleswig Holstein

Kiel, 24105, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

TU München - Klinikum rechts der Isar

München, 81675, Germany

Location

Universitatsklinik MuensterMedizinische Klinik A

Münster, 48129, Germany

Location

UKT Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

University Hospital of Ulm

Ulm, 89081, Germany

Location

Universitatsklinikum Wurzburg

Würzburg, 97080, Germany

Location

University of Athens

Athens, 11528, Greece

Location

Cork University HospitalHaematology Consultant

Wilton, Cork, Ireland

Location

Mater Misericordiae University Hospital

Dublin, Dublin 7, Ireland

Location

University Hospital Galway

Galway, ST46QG, Ireland

Location

Ospedali Riuniti di Ancona

Ancona, 60126, Italy

Location

A.O. Policlinico - Università di Bari

Bari, 70124, Italy

Location

University of Bologna

Bologna, 40138, Italy

Location

Ospedale Ferrarotto

Catania, 95124, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda, Milano

Milan, 20162, Italy

Location

Universita degli Studi di Padova

Padua, 35128, Italy

Location

Casa di Cura La Maddalena

Palermo, 90146, Italy

Location

Ospedale Civile di Piacenza

Piacenza, 29100, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, 56126, Italy

Location

Universita degli Studi di Roma La Sapienza - Azienda Policlinico Umberto I

Roma, 00168, Italy

Location

Ospedale Sant'Eugenio

Rome, 00144, Italy

Location

Azienda Ospedaliera San Giovanni Battista - Ospedale Molinette

Torino, 10126, Italy

Location

Azienda Ospedaliero-Universitaria Santa Maria della Misericordia die Udine

Udine, 33100, Italy

Location

Ospedale San Bortolo

Vicenza, 36100, Italy

Location

VU University Medical Center VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015 CE, Netherlands

Location

Haga Hospital

The Hague, 2545 CH, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Oslo University Hospital, Rikshospitalet HF

Oslo, 0424, Norway

Location

St. Olavs Hospital Trondheim

Trondheim, N-7006, Norway

Location

Akademia Medyczna w Gdansku Katedra i Klinika Hematologii i Transplantologii

Gdansk, 80-211, Poland

Location

Szpitala Uniwersyteckiego w. Krakowie

Krakow, 31 501, Poland

Location

Instytut Hematologii i Transfuzjologii w Warszawie

Warsaw, 02-776, Poland

Location

Hospital Universitario de Coimbra- Hospitais de Universidade de Coimbra

Coimbra, 3000-075, Portugal

Location

Instituto Portugues de Oncologia de Lisboa

Lisbon, 1099-023, Portugal

Location

Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Hospital Geral de Santo António - Serviço de Hematologia Clínica

Porto, 4099-001, Portugal

Location

University Hospital Bratislava - Hospital Ss Cyril and Methodius

Bratislava, 85107, Slovakia

Location

Hospital Universitari Germans Trias i Pujol

Badalona (Barcelona), 8916, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitario de Canarias

La Laguna (Tenerife), 38320, Spain

Location

Hospital de La Princesa

Madrid, 28006, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen De La Victoria

Málaga, 29010, Spain

Location

Hospital Morales Meseguer

Murcia, 30008, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital de Donosti

San Sebastián (Guipuzcoa), 20014, Spain

Location

Hospital Clinico Universitario De Santiago De Compostela

Santiago de Compostela, 15706, Spain

Location

Hospital Virgen de la Salud

Toledo, 45004, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Universitetssjukhuset i Lund

Lund, SE-22185, Sweden

Location

Karolinska University HospitalSolna

Stockholm, SE 17176, Sweden

Location

Universitatsspital Bern

Bern, 3010, Switzerland

Location

Hopitaux Universitaires de Geneve-HUG

Genèva, 1211, Switzerland

Location

University Hospital Zurich

Zurich, 8091, Switzerland

Location

Ankara University Medical Faculty Cebeci Hospital

Ankara, 06590, Turkey (Türkiye)

Location

Ege University Medical School

Izmir, 35100, Turkey (Türkiye)

Location

Belfast City Hospital Haematology Department

Belfast Northern Ireland, BT9 7AB, United Kingdom

Location

Kent and Canterbury Hospital

Canterbury/Kent, CT1 3NG, United Kingdom

Location

Leeds Teaching Hospitals Trust

Leeds, LS9 7TF, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Christie Hospital NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Newcastle Hospital Foundation Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Royal Marsden Hospital

Sutton (Surrey), SM2 5PT, United Kingdom

Location

Southmead Hospital

Westbury-on-Trym/ Bristol, BS10 5NB, United Kingdom

Location

New Cross Hospital

Wolverhampton, WV10 0QP, United Kingdom

Location

Related Publications (4)

• Dimopoulos MA, Palumbo A, Corradini P, Cavo M, Delforge M, Di Raimondo F, Weisel KC, Oriol A, Hansson M, Vacca A, Blanchard MJ, Goldschmidt H, Doyen C, Kaiser M, Petrini M, Anttila P, Cafro AM, Raymakers R, San-Miguel J, de Arriba F, Knop S, Rollig C, Ocio EM, Morgan G, Miller N, Simcock M, Peluso T, Herring J, Sternas L, Zaki MH, Moreau P. Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma. Blood. 2016 Jul 28;128(4):497-503. doi: 10.1182/blood-2016-02-700872. Epub 2016 May 25.

  PMID: 27226434 BACKGROUND

• Moreau P, Dimopoulos MA, Richardson PG, Siegel DS, Cavo M, Corradini P, Weisel K, Delforge M, O'Gorman P, Song K, Chen C, Bahlis N, Oriol A, Hansson M, Kaiser M, Anttila P, Raymakers R, Joao C, Cook G, Sternas L, Biyukov T, Slaughter A, Hong K, Herring J, Yu X, Zaki M, San-Miguel J. Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis. Eur J Haematol. 2017 Sep;99(3):199-206. doi: 10.1111/ejh.12903. Epub 2017 Jun 14.

  PMID: 28504846 BACKGROUND

• Qian X, Dimopoulos MA, Amatangelo M, Bjorklund C, Towfic F, Flynt E, Weisel KC, Ocio EM, Yu X, Peluso T, Sternas L, Zaki M, Moreau P, Thakurta A. Cereblon gene expression and correlation with clinical outcomes in patients with relapsed/refractory multiple myeloma treated with pomalidomide: an analysis of STRATUS. Leuk Lymphoma. 2019 Feb;60(2):462-470. doi: 10.1080/10428194.2018.1485915. Epub 2018 Aug 2.

  PMID: 30068263 BACKGROUND

• Siegel DS, Weisel KC, Dimopoulos MA, Baz R, Richardson P, Delforge M, Song KW, San Miguel JF, Moreau P, Goldschmidt H, Cavo M, Jagannath S, Yu X, Hong K, Sternas L, Zaki M, Palumbo A. Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and moderate renal impairment: a pooled analysis of three clinical trials. Leuk Lymphoma. 2016 Dec;57(12):2833-2838. doi: 10.1080/10428194.2016.1177181. Epub 2016 Jun 7.

  PMID: 27267105 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email:

Study Officials

• Teresa Peluso, MBBS, DCPSA

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: October 24, 2012
• Study Start: November 6, 2012
• Primary Completion: December 11, 2019
• Study Completion: December 11, 2019
• Last Updated: January 10, 2022
• Results First Posted: January 10, 2022

Record last verified: 2021-12

Locations

FR (13); IT (15); NO (2); GB (9); NL (5); BE (7); PL (3); ES (1); DK (3); AU (4); FI (2); IE (3); DE (17); PT (4); SL (1); SE (2); CH (3); TU (2); GR (1)