Clinical trial NCT01712789: Evaluation of Safety of Pomalidomide in Combination With Dexamethasone (Low Dose) in Patients With Refractory or Relapsed and Refractory Multiple Myeloma
Official title: A Multicenter, Single-arm, Open-label Study With Pomalidomide in Combination With Low Dose Dexamethasone in Subjects With Refractory or Relapsed and Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Relapsed Multiple Myeloma
Relapsed and refractory Multiple Myeloma
Pomalidomide
Dexamethasone
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2012-10-24
Enrollment: 682
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE)
timeFrame: 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:
measure: Overall Response
timeFrame: Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks
measure: Time to Response
timeFrame: Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks
measure: Kaplan Meier Estimate of Duration of Response
timeFrame: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
measure: Kaplan Meier Estimate of Progression Free Survival (PFS) According to the European Medicines Agency Guidelines
timeFrame: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
measure: Kaplan Meier Estimate of Time to Progression
timeFrame: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
measure: Kaplan Meier Estimate of Overall Survival (OS)
timeFrame: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
measure: Pomalidomide Exposure - Apparent (Oral) Clearance (CL/F)
timeFrame: Cycles 1, 2, 3, 4, 5, 6
measure: Pomalidomide Exposure - Apparent Volume of Distribution (V/F)
timeFrame: Cycles 1, 2, 3, 4, 5, 6
measure: Cytogenetic Analysis
timeFrame: Study entry
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
city: Vienna
country: Austria
facility: Wilhelminenspital Vienna
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Brugge
country: Belgium
facility: AZ St-Jan Brugge Oostende AV
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussel
country: Belgium
facility: VUB Vrije Universiteit Brussel
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege
city: Yvoir
country: Belgium
facility: CHU Mont -Godinne
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital Clinic
city: Helsinki
country: Finland
facility: Helsingin yliopistollinen keskussairaala
city: Turku
country: Finland
facility: Turku University Hospital
city: Bayonne
country: France
facility: Centre Hospitalier de la cote basque
city: Créteil
country: France
facility: Hopital Henri Mondor
city: La Tronche
country: France
facility: Hopital A. Michallon
city: Lille
country: France
facility: CHRU Claude Huriez
city: Marseille cedex
country: France
facility: Institut Paoli Calmette Hematologie
city: Nantes
country: France
facility: CHU Hotel Dieu
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: Service Hemato-Immunologie Hopital St Louis
city: Pierre Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Reims cedex
country: France
facility: CHU de Reims
city: Toulouse
country: France
facility: Hematologie - CHU Purpan
city: Tours cedex
country: France
facility: CHRU Hopital Bretonneau
city: Vandoeuvre les Nancy
country: France
facility: CHU Nancy Hematology
city: Berlin
country: Germany
facility: Charite, Campus Benjamin Franklin Universitatsmedizin Berlin
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus
city: Dusseldorf
country: Germany
facility: Universitatsklinkikum DusseldorfKlinik fur Hamatologie, Onkologie und klin. Immunoligie
city: Essen
country: Germany
facility: Universitatsklinikum Essen-
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg Medizinische Klinik und Poliklinik
city: Hamburg
country: Germany
facility: Abt Haematologie - Onkologie / Allg. Krankenhaus Altona
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Jena
country: Germany
facility: Universitatsklinikum Jena
city: Kiel
country: Germany
facility: University of Schleswig Holstein
city: Köln
country: Germany
facility: Klinikum der Universitat zu Koln
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Muenster
country: Germany
facility: Universitatsklinik MuensterMedizinische Klinik A
city: München
country: Germany
facility: TU München - Klinikum rechts der Isar
city: Tuebingen
country: Germany
facility: UKT Universitaetsklinikum Tuebingen
city: Ulm
country: Germany
facility: University Hospital of Ulm
city: Würzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Athens
country: Greece
facility: University of Athens
city: Wilton
country: Ireland
facility: Cork University HospitalHaematology Consultant
state: Cork
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Ancona
country: Italy
facility: Ospedali Riuniti di Ancona
city: Bari
country: Italy
facility: A.O. Policlinico - Università di Bari
city: Bologna
country: Italy
facility: University of Bologna
city: Catania
country: Italy
facility: Ospedale Ferrarotto
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda, Milano
city: Padova
country: Italy
facility: Universita degli Studi di Padova
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena
city: Piacenza
country: Italy
facility: Ospedale Civile di Piacenza
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: Roma
country: Italy
facility: Universita degli Studi di Roma La Sapienza - Azienda Policlinico Umberto I
city: Rome
country: Italy
facility: Ospedale Sant'Eugenio
city: Torino
country: Italy
facility: Azienda Ospedaliera San Giovanni Battista - Ospedale Molinette
city: Udine
country: Italy
facility: Azienda Ospedaliero-Universitaria Santa Maria della Misericordia die Udine
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
city: Amsterdam
country: Netherlands
facility: VU University Medical Center VU Medisch Centrum
city: Den Haag
country: Netherlands
facility: Haga Hospital
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Oslo
country: Norway
facility: Oslo University Hospital, Rikshospitalet HF
city: Trondheim
country: Norway
facility: St. Olavs Hospital Trondheim
city: Gdansk
country: Poland
facility: Akademia Medyczna w Gdansku Katedra i Klinika Hematologii i Transplantologii
city: Kraków
country: Poland
facility: Szpitala Uniwersyteckiego w. Krakowie
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii w Warszawie
city: Coimbra
country: Portugal
facility: Hospital Universitario de Coimbra- Hospitais de Universidade de Coimbra
city: Lisboa
country: Portugal
facility: Instituto Portugues de Oncologia de Lisboa
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria
city: Porto
country: Portugal
facility: Hospital Geral de Santo António - Serviço de Hematologia Clínica
city: Bratislava
country: Slovakia
facility: University Hospital Bratislava - Hospital Ss Cyril and Methodius
city: Badalona (Barcelona)
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: La Laguna (Tenerife)
country: Spain
facility: Hospital Universitario de Canarias
city: Madrid
country: Spain
facility: Hospital de La Princesa
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Universitario Virgen De La Victoria
city: Murcia
country: Spain
facility: Hospital Morales Meseguer
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: San Sebastián (Guipuzcoa)
country: Spain
facility: Hospital de Donosti
city: Santiago De Compostela
country: Spain
facility: Hospital Clinico Universitario De Santiago De Compostela
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Lund
country: Sweden
facility: Universitetssjukhuset i Lund
city: Stockholm
country: Sweden
facility: Karolinska University HospitalSolna
city: Bern
country: Switzerland
facility: Universitatsspital Bern
city: Genèva
country: Switzerland
facility: Hopitaux Universitaires de Geneve-HUG
city: Zurich
country: Switzerland
facility: University Hospital Zurich
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty Cebeci Hospital
city: Izmir
country: Turkey
facility: Ege University Medical School
city: Belfast Northern Ireland
country: United Kingdom
facility: Belfast City Hospital Haematology Department
city: Canterbury/Kent
country: United Kingdom
facility: Kent and Canterbury Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals Trust
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Foundation Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle Hospital Foundation Trust
city: Sutton (Surrey)
country: United Kingdom
facility: Royal Marsden Hospital
city: Westbury-on-Trym/ Bristol
country: United Kingdom
facility: Southmead Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: Bristol-Myers Squibb
name: Teresa Peluso, MBBS, DCPSA
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.