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

Multiple Myeloma Clinical Trial

— STRATUS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01712789
• Other study ID #: CC-4047-MM-010
• Secondary ID: 2012-001888-78
• Status: Completed
• Phase: Phase 3
• Start date: November 6, 2012
• Est. completion date: December 11, 2019

Study information

• Verified date: December 2021
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 682
• Est. completion date: December 11, 2019
• Est. primary completion date: December 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Pomalidomide
Oral Pomalidomide at the starting dose of 4 mg on Days 1-21 of a 28-day cycle
• Dexamethasone
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.

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz
Austria	Medizinische Universitat Innsbruck	Innsbruck
Austria	Medical University of Vienna	Vienna
Austria	Wilhelminenspital Vienna	Vienna
Belgium	AZ St-Jan Brugge Oostende AV	Brugge
Belgium	VUB Vrije Universiteit Brussel	Brussel
Belgium	Institut Jules Bordet	Brussels
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	Centre Hospitalier Universitaire de Liege	Liege
Belgium	CHU Mont -Godinne	Yvoir
Denmark	Aarhus University Hospital	Aarhus
Denmark	Odense University Hospital	Odense
Denmark	Vejle Hospital	Vejle
Estonia	Tartu University Hospital Clinic	Tartu
Finland	Helsingin yliopistollinen keskussairaala	Helsinki
Finland	Turku University Hospital	Turku
France	Centre Hospitalier de la cote basque	Bayonne
France	Hopital Henri Mondor	Créteil
France	Hopital A. Michallon	La Tronche
France	CHRU Claude Huriez	Lille
France	Institut Paoli Calmette Hematologie	Marseille cedex
France	CHU Hotel Dieu	Nantes
France	Hopital Saint Antoine	Paris
France	Service Hemato-Immunologie Hopital St Louis	Paris
France	Centre Hospitalier Lyon Sud	Pierre Bénite
France	CHU de Reims	Reims cedex
France	Hematologie - CHU Purpan	Toulouse
France	CHRU Hopital Bretonneau	Tours cedex
France	CHU Nancy Hematology	Vandoeuvre les Nancy
Germany	Charite, Campus Benjamin Franklin Universitatsmedizin Berlin	Berlin
Germany	Klinikum Chemnitz	Chemnitz
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	Universitatsklinkikum DusseldorfKlinik fur Hamatologie, Onkologie und klin. Immunoligie	Dusseldorf
Germany	Universitatsklinikum Essen-	Essen
Germany	Universitatsklinikum Freiburg Medizinische Klinik und Poliklinik	Freiburg
Germany	Abt Haematologie - Onkologie / Allg. Krankenhaus Altona	Hamburg
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	Universitatsklinikum Jena	Jena
Germany	University of Schleswig Holstein	Kiel
Germany	Klinikum der Universitat zu Koln	Köln
Germany	Universitatsklinikum Leipzig	Leipzig
Germany	Universitatsklinik MuensterMedizinische Klinik A	Muenster
Germany	TU München - Klinikum rechts der Isar	München
Germany	UKT Universitaetsklinikum Tuebingen	Tuebingen
Germany	University Hospital of Ulm	Ulm
Germany	Universitatsklinikum Wurzburg	Würzburg
Greece	University of Athens	Athens
Ireland	Mater Misericordiae University Hospital	Dublin
Ireland	University Hospital Galway	Galway
Ireland	Cork University HospitalHaematology Consultant	Wilton	Cork
Italy	Ospedali Riuniti di Ancona	Ancona
Italy	A.O. Policlinico - Università di Bari	Bari
Italy	University of Bologna	Bologna
Italy	Ospedale Ferrarotto	Catania
Italy	ASST Grande Ospedale Metropolitano Niguarda, Milano	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Universita degli Studi di Padova	Padova
Italy	Casa di Cura La Maddalena	Palermo
Italy	Ospedale Civile di Piacenza	Piacenza
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa
Italy	Universita degli Studi di Roma La Sapienza - Azienda Policlinico Umberto I	Roma
Italy	Ospedale Sant'Eugenio	Rome
Italy	Azienda Ospedaliera San Giovanni Battista - Ospedale Molinette	Torino
Italy	Azienda Ospedaliero-Universitaria Santa Maria della Misericordia die Udine	Udine
Italy	Ospedale San Bortolo	Vicenza
Netherlands	VU University Medical Center VU Medisch Centrum	Amsterdam
Netherlands	Haga Hospital	Den Haag
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	University Medical Center Utrecht	Utrecht
Norway	Oslo University Hospital, Rikshospitalet HF	Oslo
Norway	St. Olavs Hospital Trondheim	Trondheim
Poland	Akademia Medyczna w Gdansku Katedra i Klinika Hematologii i Transplantologii	Gdansk
Poland	Szpitala Uniwersyteckiego w. Krakowie	Kraków
Poland	Instytut Hematologii i Transfuzjologii w Warszawie	Warszawa
Portugal	Hospital Universitario de Coimbra- Hospitais de Universidade de Coimbra	Coimbra
Portugal	Hospital de Santa Maria	Lisboa
Portugal	Instituto Portugues de Oncologia de Lisboa	Lisboa
Portugal	Hospital Geral de Santo António - Serviço de Hematologia Clínica	Porto
Slovakia	University Hospital Bratislava - Hospital Ss Cyril and Methodius	Bratislava
Spain	Hospital Universitari Germans Trias i Pujol	Badalona (Barcelona)
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario de Canarias	La Laguna (Tenerife)
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital de La Princesa	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario Virgen De La Victoria	Malaga
Spain	Hospital Morales Meseguer	Murcia
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital de Donosti	San Sebastián (Guipuzcoa)
Spain	Hospital Clinico Universitario De Santiago De Compostela	Santiago De Compostela
Spain	Hospital Virgen de la Salud	Toledo
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Sweden	Universitetssjukhuset i Lund	Lund
Sweden	Karolinska University HospitalSolna	Stockholm
Switzerland	Universitatsspital Bern	Bern
Switzerland	Hopitaux Universitaires de Geneve-HUG	Genèva
Switzerland	University Hospital Zurich	Zurich
Turkey	Ankara University Medical Faculty Cebeci Hospital	Ankara
Turkey	Ege University Medical School	Izmir
United Kingdom	Belfast City Hospital Haematology Department	Belfast Northern Ireland
United Kingdom	Kent and Canterbury Hospital	Canterbury/Kent
United Kingdom	Leeds Teaching Hospitals Trust	Leeds
United Kingdom	Royal Liverpool University Hospital	Liverpool
United Kingdom	Christie Hospital NHS Foundation Trust	Manchester
United Kingdom	Newcastle Hospital Foundation Trust	Newcastle upon Tyne
United Kingdom	Royal Marsden Hospital	Sutton (Surrey)
United Kingdom	Southmead Hospital	Westbury-on-Trym/ Bristol
United Kingdom	New Cross Hospital	Wolverhampton

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  Estonia,  Finland,  France,  Germany,  Greece,  Ireland,  Italy,  Netherlands,  Norway,  Poland,  Portugal,  Slovakia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

References & 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, Röllig 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. — View 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. — View 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. — View 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. Epub 2016 Jun 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Response	Overall response rate (ORR) was defined as the percentage of participants with a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) according to the International Myeloma Working Group uniform response criteria (IMWG URC) assessed by the Investigator. Responses must have been confirmed at at least 2 consecutive assessments before the institution of any new therapy with no known evidence of progressive or new bone lesions	Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks
Secondary	Time to Response	Time to response was defined as the time from treatment enrollment to the first documentation of response (sCR, CR, VGPR or PR) based on IMWG criteria.	Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks
Secondary	Kaplan Meier Estimate of Duration of Response	Duration of response, calculated for responders only, was defined as time from the initial documented response (SCR, CR, VGPR or PR) to the first confirmed disease progression, or death if no disease progression was recorded. Participants without a documented progression were censored at the time of their last tumor assessment.	From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
Secondary	Kaplan Meier Estimate of Progression Free Survival (PFS) According to the European Medicines Agency Guidelines	Progression free survival was calculated as the time from study enrollment, defined as the IVRS enrollment date, until either PD or death (any cause). Participants without an event (either a documented PD or death) at the time of study end were censored at the time of their last documented disease assessment or at the IVRS enrollment date if no disease assessment was conducted.	From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
Secondary	Kaplan Meier Estimate of Time to Progression	Time to progression was calculated as the time from study enrollment until first recorded disease progression as determined by the site investigator based on the IMWG criteria, or until death due to progression. Participants not experiencing a documented progression were censored at the time of their last tumor assessment (or at the time of trial enrollment if no assessment was conducted).	From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
Secondary	Kaplan Meier Estimate of Overall Survival (OS)	Overall survival was calculated as the time from study enrollment, defined as the IVRS enrollment date, until death due to any cause. Participants who did not have death data at the time of study end/analysis were censored at the time they were last known to be alive.	From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
Secondary	Pomalidomide Exposure - Apparent (Oral) Clearance (CL/F)	Pharmacokinetic (PK) parameters are derived from pomalidomide concentration versus time data.	Cycles 1, 2, 3, 4, 5, 6
Secondary	Pomalidomide Exposure - Apparent Volume of Distribution (V/F)	Pharmacokinetic (PK) parameters are derived from Pomalidomide concentration versus time data.	Cycles 1, 2, 3, 4, 5, 6
Secondary	Cytogenetic Analysis	Cytogenetic analysis was to be performed using fluorescence in situ hybridization (FISH) methodology at a local laboratory, to evaluate the relationship between cytogenetic profiles and the combination of POM and LD-DEX in terms of response and outcome.	Study entry