Study to Evaluate the Safety and Efficacy of Pomalidomide Monotherapy in Subjects With Refractory or Relapsed Refractory Multiple Myeloma

NCT01324947 | Completed Phase 3 Results

• 2 other identifiers: CC-4047-MM-003/C2010-023343-16
• Study Type: interventional
• Target: 74
• Locations: 15 countries
• Sites: 91

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of pomalidomide monotherapy in subjects with refractory or relapsed and refractory multiple myeloma who were enrolled in study CC-4047-MM-003 (NCT01311687) and discontinued treatment with high-dose dexamethasone due to disease progression.

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; Companion

Outcome Measures

Primary Outcomes (1)

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

  Objective response defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on Investigator Assessment. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours. A ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.

  From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum time on follow-up was 141.1 weeks.

Secondary Outcomes (7)

• Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria Based on Investigator Assessment

  From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum time on follow-up was 141.1 weeks.

• Number of Participants With Adverse Events and Type of Adverse Events

  From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 31 July 2014. Maximum time on treatment was 94.1 weeks.

• Kaplan Meier Estimates for Progression Free Survival (PFS) by Investigator Based on IMWG

  From randomization through the follow-up phase; Maximum duration of follow-up for PFS was 90.3 weeks.

• Kaplan-Meier Estimate for Time to Progression (TTP) Based on Investigator Assessment Using IMWG Criteria

  From randomization through the follow-up phase; up to the data-cut off of 31 July 2014; Maximum time to progression follow-up was 90.3 weeks.

• Kaplan-Meier Estimate Duration of Response Based on Investigator Assessment Using IMWG Criteria

  From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum duration of response follow-up was 90.3 weeks.

Study Arms (1)

Pomalidomide

EXPERIMENTAL

Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity

Drug: pomalidomide

Interventions

pomalidomide DRUG

Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity

Also known as: CC-4047

Pomalidomide

Eligibility Criteria

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

You may qualify if:

• Subjects with refractory or relapsed and refractory multiple myeloma who were enrolled in Study CC-4047-MM-003 and discontinued study therapy with dexamethasone alone (Treatment Arm B) after at least starting the second cycle of dexamethasone treatment and due to development of documented disease progression according to the International Myeloma Working Group (IMWG) criteria and as decided by an Independent Review Adjudication Committee (IRAC).
• Must be ≥ 18 years at the time of signing the informed consent form.
• The subject must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted. The only exception is if a skeletal survey was performed within 90 days prior to the start of Cycle 1, then a new survey will not be required.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Subjects must have documented diagnosis of multiple myeloma and have measurable disease (serum M-protein ≥ 0.5g/dL or urine M-protein ≥ 200 mg/24 hours).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Females of childbearing potential (FCBP†) must agree to utilize two reliable forms of contraception simultaneously or practice true abstinence \[when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception\]from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 28 days after study treatment discontinuation and must agree to regular pregnancy testing during this timeframe.
• Females must agree to abstain from breastfeeding during study participation and 28 days after study discontinuation.
• Males must agree to either use a latex condom during any sexual contact with FCBP or practice true abstinence \[when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\] while participating in the study and for 28 days following discontinuation from this study, even if he has undergone a successful vasectomy. .
• Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study treatment.
• All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment.
• All subjects must agree not to share study medication

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subjects with multiple myeloma who were not treated as a part of Study CC-4047-MM-003 (Arm B).
• Subjects who received any anti-myeloma or anti-cancer therapies within the last 14 days of wash-out period before initiation of study treatment.
• Subjects who discontinued CC-4047-MM-003 study ≥120 days.
• Subjects who initiate another anti-myeloma therapy from the time of disease progression on study CC-4047-MM-003 to the time of treatment initiation in the companion study.
• 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; or a platelet count \< 30,000/µL for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells
• Creatinine Clearance \< 45 mL/min according to Cockcroft-Gault formula (If creatinine clearance calculated from the 24-hour urine sample is ≥45 ml/min, patient will qualify for the trial)
• Corrected serum calcium \> 14 mg/dL (\> 3.5 mmol/L);
• Hemoglobin \< 8 g/dL (\< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted)
• Serum SGOT/AST or SGPT/ALT \> 3.0 x upper limit of normal (ULN)
• Serum total bilirubin \> 2.0 mg/dL (34.2 μmol/L); or \> 3.0 x ULN for subjects with hereditary benign hyperbilirubinaemia
• Prior history of malignancies, other than Multiple Myeloma (MM), unless the subject has been free of the disease for ≥ 5 years. Exceptions include the following:
• Basal or Squamous cell carcinoma of the skin

Sponsors & Collaborators

• Celgene: lead

Study Sites (91)

Royal Adelaide Hospital - SA Pathology Haematology

Adelaide, 5000, Australia

Location

Princess Alexandra Hospital - Haematology

Brisbane, 4102, Australia

Location

Royal Prince Alfred Hospital - Institute of Haematology

Camperdown, 2050, Australia

Location

Peter McCallum Cancer Institute - Directorate of Cancer Medicine

East Melbourne, 3002, Australia

Location

Frankston Hospital-Peninsula Health - Oncology Day Unit

Frankston, 3199, Australia

Location

The Alfred Hospital - Malignant Haematology & Stem Cell Transplantation

Melbourne, 3004, Australia

Location

Calvary Mater Newcastle - Haematology

Waratah, 2298, Australia

Location

Border Medical Oncology

Wodonga, 3690, Australia

Location

Wollongong Hospital - Haematology

Wollongong, 2500, Australia

Location

UZ Gent - Hematology

Ghent, 9000, Belgium

Location

University Hospital Leuven - Hematology

Leuven, 3000, Belgium

Location

Cliniques Universitaires ULC de Mont-Godinne - Hematology

Yvoir, 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 Centre

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Princess Margaret Hospital, University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

Royal Victoria Hospital

Montreal, Quebec, H3A1 A1, Canada

Location

Charles University Hospital - Internal Medicine

Prague, 12808, Czechia

Location

Aalborg Sygemus - Haematology

Aalborg, 9000, Denmark

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Odense University Hospital

Odense, 5000, Denmark

Location

Vejle Hospital - Hematology

Vejle, 7100, Denmark

Location

CHU Angers - Service des maladies du sang

Angers, 49033, France

Location

Centre Hospitalier de la côte basque - Hematologie

Bayonne, 64019, France

Location

Centre Hospitalier Départemental Vendée - Onco-hematologie

La Roche, 85925, France

Location

CHRU de Lille - Service des maladies du sang

Lille, 59037, France

Location

Institut Paoli Calmette - Hematology 1

Marseille, 13009, France

Location

CHU Hôtel-Dieu - Hematologie

Nantes, 44093, France

Location

Hôpital Saint Louis - Immuno-hematologie

Paris, 75010, France

Location

CHU Saint Antoine - Service des maladies du sang

Paris, 75012, France

Location

CHRU - Hôpital du Haut Lévêque - Centre François Magendie Service des maladies du sang

Pessac, 33604, France

Location

Centre Hospitalier Lyon sud - Hematologie

Pierre-Bénite, 69495, France

Location

CHRU Hôpital Purpan - Hematologie

Toulouse, 31059, France

Location

Hôpital Bretonneau - Hématologie & Thérapie cellulaire

Tours, 37044, France

Location

CHU Nancy - Hematologie

Vandœuvre-lès-Nancy, 54511, France

Location

Universitatsklinikum Carl Gustav Carus-Medizinische Klinik und Poliklinik I

Dresden, 01307, Germany

Location

Universitätsklinikum Essen, Klinik für Hämatologie Westdeutsches Tumorzentrum

Essen, 45122, Germany

Location

Askepios Klinik Altona-Abteilung Hamatologie und Internistische Onkologie

Hamburg, 22763, Germany

Location

Universitätsklinikum Heidelberg - Medizinische Klinik und Poliklinik V

Heidelberg, 69120, Germany

Location

Universitätsklinikum Jena - Klinik fur Innere Medizin II-Hamatologie/Onkologie

Jena, 07740, Germany

Location

Universitätsklinikum Leipzig - Medizinische Klinik und Poliklinik II

Leipzig, 04103, Germany

Location

Universitätsklinikum Münster - Medizinische Klinik und Poliklinik A

Münster, 48149, Germany

Location

Universitätsklinikum Tübingen - Medizinische Klinik und Poliklinik - Abteilung II

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm - Klinik fur Innere Medizin III

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg - Medizinische Klinik und Poliklinik II

Würzburg, 97080, Germany

Location

University of Athens - Alexandra Hospital

Athens, 14572, Greece

Location

Università degli Studi di Bologna - Policlinico S. Orsola - Hematology

Bologna, 40138, Italy

Location

AO Universitaria San Martino - hematooncology

Genova, 16132, Italy

Location

Fondazione "G. Pascale" - Hematology

Napoli, 80131, Italy

Location

Ospedale San Luigi AO Luigi Gonzaga - Hematology

Orbassano, 10043, Italy

Location

Universita degli Studi di Padova - Clinical & Experimental Medicine

Padua, 35128, Italy

Location

Ospedale Guglielmo da Saliceto - hematooncology

Piacenza, 29100, Italy

Location

Unità di Ematologia Arcispedale S. Maria Nuova - Haematology

Reggio Emilia, 42100, Italy

Location

Policlinico Umberto I, Università "La Sapienza" di Roma - Hematology

Roma, 00161, Italy

Location

A.O.U. San Giovanni Battista - Hematology

Torino, 10126, Italy

Location

VUMC - Hematology

Amsterdam, 1081 HV, Netherlands

Location

Erasmus Medical Center - Hematology

Rotterdam, 3015 CE, Netherlands

Location

University Medical Center - Hematology

Utrecht, 3584 CX, Netherlands

Location

Hematological Research Center under the Russian Academy of Medical Sciences - Hematology & BMT

Moscow, 125167, Russia

Location

Moscow State Medical Institution Municipal Clinical Hospital n.a. S.P. Botkin - Hematology

Moscow, 125284, Russia

Location

Russian Research Institute of Hematology and Blood Transfusion - Hematology

Saint Petersburg, 191024, Russia

Location

State Higher Educational Institution St. Petersburg State Medical University - Onco-hematology

Saint Petersburg, 197341, Russia

Location

Hospital Germans Trias i Pujol - Hematology

Badalona, 08916, Spain

Location

Hospital Clinic i Provincial de Barcelona - Hematology

Barcelona, 08036, Spain

Location

Hospital de Donostia - Hematology

Guipúzcoa, 20014, Spain

Location

Hospital de La Princesa - Hematology

Madrid, 28006, Spain

Location

Hospital 12 de Octubre - Hematology

Madrid, 28041, Spain

Location

Hospital de Salamanca - Hematology

Salamanca, 37007, Spain

Location

Hospital Universitario Marqués de Valdecilla - Hematology

Santander, 39008, Spain

Location

Hospital La Fe - Hematology

Valencia, 46009, Spain

Location

Sahlgrenska Hospital, University of Goteborg - Hematology

Gothenburg, S-41345, Sweden

Location

Karolinska University Hospital Huddinge - Center of hematology

Stockholm, 14152, Sweden

Location

Karolinska University Hospital-medicine

Stockholm, 14186, Sweden

Location

Karolinska University Hospital Solna- medicine

Stockholm, 17176, Sweden

Location

Overlakare Medocomcentrum - Hematology

Uppsala, 75185, Sweden

Location

Inselspital, Institut für Medizinische Onkologie

Bern, 3010, Switzerland

Location

Hôpitaux Universitaire de Genève - Oncologie

Geneva, 1211, Switzerland

Location

Klinik und Poliklinik für Onkologie - UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Royal Bournemouth Hospital - Haematology

Bournemouth, BH7 7DW, United Kingdom

Location

St James's University Hospital - Haematology

Leeds, LS9 7TF, United Kingdom

Location

St Bartholomew's Hospital - Medical Oncology

London, EC1A 7BE, United Kingdom

Location

King's College Hospital - Haematology Clinical Trials

London, SE5 9RS, United Kingdom

Location

Freeman Hospital - Northern Centre for Cancer Care

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Nottingham City Hospital - Centre for Clinical Haematology

Nottingham, NG5 1PB, United Kingdom

Location

Derriford Hospital - Haematology

Plymouth, PL6 8DH, United Kingdom

Location

Royal hallamshire Hospital - Haematology

Sheffield, S10 2JF, United Kingdom

Location

Royal Marsden NHS Foundation Trust - Haematology

Surrey, SM2 5PT, United Kingdom

Location

Royal Wolverhampton Hospitals Trust - Research and Development

Wolverhampton, WV10 OQP, United Kingdom

Location

Related Publications (3)

• 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 BACKGROUND

• 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 BACKGROUND

• Morgan G, Palumbo A, Dhanasiri S, Lee D, Weisel K, Facon T, Delforge M, Oriol A, Zaki M, Yu X, Sternas L, Jacques C, Akehurst R, Offner F, Dimopoulos MA. Overall survival of relapsed and refractory multiple myeloma patients after adjusting for crossover in the MM-003 trial for pomalidomide plus low-dose dexamethasone. Br J Haematol. 2015 Mar;168(6):820-3. doi: 10.1111/bjh.13227. Epub 2014 Nov 18.

  PMID: 25403264 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Recurrence

Interventions

pomalidomide

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

Results Point of Contact

• Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

888-260-1599

Study Officials

• Mohamed Zaki, MD, PhD

  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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2011
• First Posted: March 29, 2011
• Study Start: March 1, 2011
• Primary Completion: July 31, 2014
• Study Completion: July 31, 2014
• Last Updated: November 19, 2019
• Results First Posted: July 30, 2015

Record last verified: 2019-11

Locations

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