A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Subjects With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study

NCT01311687 | Completed Phase 3 Results DMC

• 2 other identifiers: CC-4047-MM-0032010-019820-30
• Study Type: interventional
• Target: 455
• Locations: 16 countries
• Sites: 94

Brief Summary

The purpose of this study is to compare efficacy and safety of pomalidomide in combination with low-dose dexamethasone versus high-dose dexamethasone in subjects with refractory or relapsed and refractory multiple myeloma.

Conditions

Multiple Myeloma

Keywords

Myeloma; Multiple Myeloma; Relapsed Multiple Myeloma; Relapsed and Refractory Multiple Myeloma; Refractory Myeloma; Resistant Multiple Myeloma; Treatment-resistant Multiple Myeloma; Pomalidomide; Lenalidomide-resistant; Bortezomib-resistant

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) - Primary Analysis

  Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease required 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.

  From randomization until the data cut-off date of 07 September 2012. Maximum duration of follow-up for PFS assessments was 57 weeks.

• Progression-free Survival (PFS) With a Later Cut-off Date

  Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.

  From randomization until the data cut-off date of 01 March 2013. Maximum duration of follow-up for PFS assessments was 74 weeks.

Secondary Outcomes (22)

• Number of Participants With Adverse Events (AEs)

  From first dose of study drug through to 30 days after the last dose as of the end of the study (29 August 2017); maximum time on treatment was 297, 269, and 239 weeks in the Pomalidomide + LD-Dex, HD-Dex, and cross-over groups respectively.

• Overall Survival - Primary Analysis

  From randomization until the data cut-off date of 07 September 2012. Maximum time on follow-up for survival was 70 weeks.

• Overall Survival With a Later Cut-off Date

  From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up for survival was 93 weeks.

• Overall Survival Based on the Final Dataset

  From randomization until the data cut-off date of 29 August 2017. Maximum time on follow-up for survival was 324 weeks.

• Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria

  From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.

Study Arms (2)

Pomalidomide + Low-Dose Dexamethasone

EXPERIMENTAL

Participants received 4 mg pomalidomide administered by mouth on Days 1 to 21 of each 28-day treatment cycle and 40 mg dexamethasone (or 20 mg for participants \> 75 years of age) administered by mouth once per day on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression.

Drug: pomalidomide; Drug: Dexamethasone

High-Dose Dexamethasone

ACTIVE COMPARATOR

Participants received 40 mg dexamethasone (or 20 mg for participants \> 75 years of age) administered by mouth once per day on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day treatment cycle until disease progression.

Drug: Dexamethasone

Interventions

pomalidomide DRUG

4 mg pomalidomide capsules administered orally

Also known as: CC-4047, Pomalyst®

Pomalidomide + Low-Dose Dexamethasone

Dexamethasone DRUG

40 mg dexamethasone (or 20 mg for participants \> 75 years of age) tablets administered orally

High-Dose Dexamethasone; Pomalidomide + Low-Dose Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Must be ≥ 18 years of age
• Subjects must have documented diagnosis of multiple myeloma and have measurable disease
• Subjects must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy
• Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy
• All subjects must have received at least 2 consecutive cycles of prior treatment that included lenalidomide and bortezomib
• All subjects must have failed treatment with both lenalidomide and bortezomib in one of the following ways: 1) Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or bortezomib, or 2) In case of prior response \[≥ partial response (PR)\] to lenalidomide or bortezomib, subjects must have relapsed within 6 months after stopping treatment with lenalidomide and/or bortezomib-containing regimens, or 3) Subjects who have not had a ≥ minimal response (MR) and have developed intolerance/toxicity after a minimum of two cycles of lenalidomide- and/or bortezomib-containing regimen
• Patients must have received adequate prior alkylator therapy
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Females of childbearing potential (FCBP) must not become pregnant for 28 days prior to initiation of study drug, during the study, and for 28 days after discontinuation
• Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation
• Males must agree to use a latex condom during any sexual during the study and for 28 days following discontinuation from this study
• Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study

You may not qualify if:

• Any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) \< 1,000/μL
• Platelet count \< 75,000/ μL for subjects in whom \< 50% of bone marrow nucleated cells are plasma cells
• Creatinine clearance \< 45 mL/min
• Corrected serum calcium \> 14 mg/dL
• Hemoglobin ≤ 8 g/dL
• Serum glutamic oxaloacetic transaminase (SGOT)/ aspartate aminotransferase (AST) or transaminase, serum glutamic pyruvic (SGPT)/ alanine aminotransferase (ALT) \> 3.0 x upper limit of normal (ULN)
• Serum total bilirubin \> 2.0 mg/dL
• Previous therapy with pomalidomide
• Hypersensitivity to thalidomide, lenalidomide, or dexamethasone
• Resistance to high-dose dexamethasone used in the last line of therapy
• Peripheral neuropathy ≥ Grade 2
• Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant
• Subjects who are planning for or who are eligible for stem cell transplant
• Subjects with any one of the following: 1) Congestive heart failure, 2) Myocardial infarction within 12 months prior to starting study treatment, 3) Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris

Sponsors & Collaborators

• Celgene: lead

Study Sites (94)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Peter MacCallum Cancer Institute

East Melbourne, Victoria, 3002, Australia

Location

Frankston Hospital

Frankston, Victoria, 3199, Australia

Location

Princess Alexandra Hospital

Brisbane, QLD4102, Australia

Location

Royal Prince Alfred Hospital

Camperdown, 2050, Australia

Location

Alfred hospital

Melbourne, 3004, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, 6009, Australia

Location

Calvary Mater Hospital

Waratah, NSW 2298, Australia

Location

Border Medical Oncology

Wodonga, 3690, Australia

Location

Wollongong Hospital

Wollongong, 2500, Australia

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHU UCL Mont-Godinne-Dinant asbl

Yvoir, B-5530, Belgium

Location

Tom Baker Cancer Center

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

British Columbia Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

James Cancer Hospital

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

London Health Sciences Centre

London, Ontario, N6C 6B5, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Maisonneuve Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Royal Victoria Hospital McGill Department of Oncology(RVH)

Montreal, Quebec, H3A 1A1, Canada

Location

Sir Mortimer B. Davis - Jewish Genl

Montreal, Quebec, H3T 1E2, Canada

Location

Charles University General Hospital

Prague, 128 08, Czechia

Location

Hæmatologisk afd. B Aalborg Sygehus Syd

Aalborg, 9000, Denmark

Location

Aarhus University Hospital

Arhus C, DK-8000, Denmark

Location

Odense Universitetshospital

Odense C, 5000, Denmark

Location

Vejle Hospital

Vejle, 7100, Denmark

Location

CHU d'Angers

Angers, 49033, France

Location

Centre Hospitalier de la cote basque

Bayonne, 64109, France

Location

Centre Hospitalier Departemental

La Roche-sur-Yon, 85025, France

Location

CHRU de Lille FR

Lille, 59037, France

Location

Institut Paoli-Calmettes

Marseille, 13009, France

Location

CHRU Nantes

Nantes, 44093, France

Location

Hopital Saint-Louis

Paris, 75475, France

Location

CHU Hôpital St-Antoine

Paris, 75571, France

Location

CHRU - Hopital du Haut Leveque

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69310, France

Location

Hopital Bretonneau

Tours, 37044, France

Location

Hopital Purpan

Tulouse Cedex 9, 31059, France

Location

CHU Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

Universitatsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Universitatsklinikum Essen

Essen, 45122, Germany

Location

Askepios Klinik St. Georg

Hamburg, 20099, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitatsklinikum Jena

Jena, 07740, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

University of Tubingen

Tübingen, 72076, Germany

Location

Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

Universitatsklinikum Wurzburg

Würzburg, 97080, Germany

Location

Alexandra General Hospital of Athens

Athens, 11528, Greece

Location

Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi

Bologna, 40138, Italy

Location

Clinica Ematologica- A.O.U. San Martino

Genova, 16132, Italy

Location

Oncoematologia, Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, 80131, Italy

Location

AOU San Luigi Gonzaga

Orbassano, 10043, Italy

Location

Universita degli Studi di Padova

Padua, 35128, Italy

Location

Hospital Clinic

Placenza, 29100, Italy

Location

Servizio di Ematologia, A.O. - Arcispedale S.Maria Nuova

Reggio Emilia, 42100, Italy

Location

Univerita La Sapienza Dipartimento di Biotecnologie Cellulari ed Ematologia

Rome, 00161, Italy

Location

Azienda Ospedaliera San Giovanni Battista

Torino, 10126, Italy

Location

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015 CE, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

State Institution Hematological Research, Centre of Russian Academy of Medical Science

Moscow, 125167, Russia

Location

State Institution Moscow Regional Research Clinical Institute

Moscow, 125284, Russia

Location

St. Petersburg Research Institute of Hematology and Blood Transfusion

Saint Petersburg, 191024, Russia

Location

State Educational Institution, Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

Hospital Universitari Germans Trias i Pujol

Badalona (Barcelona), 08916, Spain

Location

Hospital Clinic Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital de La Princesa

Madrid, 28006, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Donostia

San Sebastián (Guipuzcoa), 20014, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital de la Fe

Valencia, 46009, Spain

Location

Department of Hematology Hematology Centre

Gothenburg, S-413 45, Sweden

Location

University Hospital in Lund

Lund, 221 85, Sweden

Location

Karolinska University Hospital Huddinge

Stockholm, SE 17176, Sweden

Location

Karolinska University Hospital

Stockholm, SE-171 76, Sweden

Location

Overlakare Medocomcentrum, hematologi

Uppsala, 75185, Sweden

Location

Medizinische Universitatsklinik

Bern, CH - 3010, Switzerland

Location

Hopitaux Universitaires de Geneve-HUG

Geneva, 1205, Switzerland

Location

UniversitatSspital Zurich

Zurich, 8091, Switzerland

Location

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

St.Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Royal Hallamshire HospitalSheffield Teaching Hospitals NHS Trust

Sheffield, S10 2JF, United Kingdom

Location

The Royal Marsden Hospital

Sutton-Surrey, SM2 5PT, United Kingdom

Location

The Royal Wolverhampton Hospital NHS Trust

Wolverhampton, WV10 0QP, United Kingdom

Location

Related Publications (8)

• Moreau P, Weisel KC, Song KW, Gibson CJ, Saunders O, Sternas LA, Hong K, Zaki MH, Dimopoulos MA. Relationship of response and survival in patients with relapsed and refractory multiple myeloma treated with pomalidomide plus low-dose dexamethasone in the MM-003 trial randomized phase III trial (NIMBUS). Leuk Lymphoma. 2016 Dec;57(12):2839-2847. doi: 10.1080/10428194.2016.1180685. Epub 2016 May 13.

  PMID: 27173785 RESULT

• Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-1066. doi: 10.1016/S1470-2045(13)70380-2. Epub 2013 Sep 3.

  PMID: 24007748 RESULT

• 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 DERIVED

• Weisel KC, Dimopoulos MA, Moreau P, Lacy MQ, Song KW, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Knop S, Yu X, Hong K, Sternas L, Jacques C, Zaki MH, San Miguel J. Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma. Haematologica. 2016 Jul;101(7):872-8. doi: 10.3324/haematol.2015.137083. Epub 2016 Apr 14.

  PMID: 27081177 DERIVED

• Dimopoulos MA, Weisel KC, Song KW, Delforge M, Karlin L, Goldschmidt H, Moreau P, Banos A, Oriol A, Garderet L, Cavo M, Ivanova V, Alegre A, Martinez-Lopez J, Chen C, Spencer A, Knop S, Bahlis NJ, Renner C, Yu X, Hong K, Sternas L, Jacques C, Zaki MH, San Miguel JF. Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone. Haematologica. 2015 Oct;100(10):1327-33. doi: 10.3324/haematol.2014.117077. Epub 2015 Aug 6.

  PMID: 26250580 DERIVED

• San Miguel JF, Weisel KC, Song KW, Delforge M, Karlin L, Goldschmidt H, Moreau P, Banos A, Oriol A, Garderet L, Cavo M, Ivanova V, Alegre A, Martinez-Lopez J, Chen C, Renner C, Bahlis NJ, Yu X, Teasdale T, Sternas L, Jacques C, Zaki MH, Dimopoulos MA. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. Haematologica. 2015 Oct;100(10):1334-9. doi: 10.3324/haematol.2015.125864. Epub 2015 Jul 9.

  PMID: 26160879 DERIVED

• Weisel K, Dimopoulos M, Song KW, Moreau P, Palumbo A, Belch A, Schey S, Sonneveld P, Sternas L, Yu X, Amatya R, Gibson CJ, Zaki M, Jacques C, San Miguel J. Pomalidomide and Low-Dose Dexamethasone Improves Health-Related Quality of Life and Prolongs Time to Worsening in Relapsed/Refractory Patients With Multiple Myeloma Enrolled in the MM-003 Randomized Phase III Trial. Clin Lymphoma Myeloma Leuk. 2015 Sep;15(9):519-30. doi: 10.1016/j.clml.2015.05.007. Epub 2015 Jun 6.

  PMID: 26149712 DERIVED

• Song KW, Dimopoulos MA, Weisel KC, Moreau P, Palumbo A, Belch A, Schey S, Sonneveld P, Sternas L, Yu X, Amatya R, Monzini MS, Zaki M, Jacques C, San Miguel J. Health-related quality of life from the MM-003 trial of pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed and/or refractory multiple myeloma. Haematologica. 2015 Feb;100(2):e63-7. doi: 10.3324/haematol.2014.112557. Epub 2014 Nov 25. No abstract available.

  PMID: 25425684 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Recurrence

Interventions

pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

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: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

1-888-260-1599

Study Officials

• Lars Sternas, MD, PhD

  Celgene

  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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2011
• First Posted: March 9, 2011
• Study Start: March 11, 2011
• Primary Completion: March 1, 2013
• Study Completion: August 29, 2017
• Last Updated: October 24, 2018
• Results First Posted: April 30, 2014

Record last verified: 2018-09

Locations

GB (10); BE (3); NL (3); FR (13); US (1); GR (1); IT (9); CZ (1); CA (10); DE (9); SE (5); RU (4); ES (8); CH (3); DK (4); AU (10)