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

NCT ID: NCT01324947

Last Updated: 2019-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-01
• Study Completion Date: 2014-07-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pomalidomide

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

Group Type: EXPERIMENTAL

pomalidomide

Intervention Type: DRUG

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

Interventions

pomalidomide

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

Intervention Type: DRUG

Other Intervention Names

CC-4047

Eligibility Criteria

Inclusion Criteria

1. 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).

2. Must be ≥ 18 years at the time of signing the informed consent form.

3. 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.

4. Must be able to adhere to the study visit schedule and other protocol requirements.

5. 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).

6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

7. 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.

8. Females must agree to abstain from breastfeeding during study participation and 28 days after study discontinuation.

9. 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. .

10. Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study treatment.

11. All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment.

12. All subjects must agree not to share study medication

Exclusion Criteria

• The presence of any of the following will exclude a subject from enrollment:

1. Subjects with multiple myeloma who were not treated as a part of Study CC-4047-MM-003 (Arm B).

2. Subjects who received any anti-myeloma or anti-cancer therapies within the last 14 days of wash-out period before initiation of study treatment.

3. Subjects who discontinued CC-4047-MM-003 study ≥120 days.

4. 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.

5. 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

6. 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
• Carcinoma in situ of the cervix or breast
• Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)

7. Hypersensitivity to thalidomide or lenalidomide. (This includes ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy).

8. Peripheral neuropathy ≥ Grade 2.

9. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study treatment and who have not discontinued immunosuppressive treatment for at least 4 weeks prior to initiation of study treatment and are currently dependent on such treatment.

10. Subjects who are planning for or who are eligible for stem cell transplant.

11. Subjects with any one of the following:

• Congestive heart failure (NY Heart Association Class III or IV)
• Myocardial infarction within 12 months prior to starting study treatment
• Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris

12. Subjects who received any of the following within the last 14 days of initiation of study treatment:

• Plasmapheresis
• Major surgery (kyphoplasty is not considered major surgery)
• Radiation therapy

13. Use of any investigational agents within 28 days or 5 half lives (whichever is longer) of treatment.

14. Subjects with chronic conditions such as rheumatoid arthritis, multiple sclerosis and lupus, which likely need additional steroid or immunosuppressive treatments in addition to the study treatment.

15. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

16. Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide.

17. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.

18. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

19. Pregnant or breastfeeding females.

20. Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis A, B or C.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohamed Zaki, MD, PhD

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

Royal Adelaide Hospital - SA Pathology Haematology

Adelaide, , Australia

Princess Alexandra Hospital - Haematology

Brisbane, , Australia

Royal Prince Alfred Hospital - Institute of Haematology

Camperdown, , Australia

Peter McCallum Cancer Institute - Directorate of Cancer Medicine

East Melbourne, , Australia

Frankston Hospital-Peninsula Health - Oncology Day Unit

Frankston, , Australia

The Alfred Hospital - Malignant Haematology & Stem Cell Transplantation

Melbourne, , Australia

Calvary Mater Newcastle - Haematology

Waratah, , Australia

Border Medical Oncology

Wodonga, , Australia

Wollongong Hospital - Haematology

Wollongong, , Australia

UZ Gent - Hematology

Ghent, , Belgium

University Hospital Leuven - Hematology

Leuven, , Belgium

Cliniques Universitaires ULC de Mont-Godinne - Hematology

Yvoir, , Belgium

Tom Baker Cancer Center

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

British Columbia Cancer Agency, Vancouver Centre

Vancouver, British Columbia, Canada

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

London Health Sciences Centre

London, Ontario, Canada

Princess Margaret Hospital, University Health Network

Toronto, Ontario, Canada

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

Royal Victoria Hospital

Montreal, Quebec, Canada

Charles University Hospital - Internal Medicine

Prague, , Czechia

Aalborg Sygemus - Haematology

Aalborg, , Denmark

Aarhus University Hospital

Aarhus, , Denmark

Odense University Hospital

Odense, , Denmark

Vejle Hospital - Hematology

Vejle, , Denmark

CHU Angers - Service des maladies du sang

Angers, , France

Centre Hospitalier de la côte basque - Hematologie

Bayonne, , France

Centre Hospitalier Départemental Vendée - Onco-hematologie

La Roche, , France

CHRU de Lille - Service des maladies du sang

Lille, , France

Institut Paoli Calmette - Hematology 1

Marseille, , France

CHU Hôtel-Dieu - Hematologie

Nantes, , France

Hôpital Saint Louis - Immuno-hematologie

Paris, , France

CHU Saint Antoine - Service des maladies du sang

Paris, , France

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

Pessac, , France

Centre Hospitalier Lyon sud - Hematologie

Pierre-Bénite, , France

CHRU Hôpital Purpan - Hematologie

Toulouse, , France

Hôpital Bretonneau - Hématologie & Thérapie cellulaire

Tours, , France

CHU Nancy - Hematologie

Vandœuvre-lès-Nancy, , France

Universitatsklinikum Carl Gustav Carus-Medizinische Klinik und Poliklinik I

Dresden, , Germany

Universitätsklinikum Essen, Klinik für Hämatologie Westdeutsches Tumorzentrum

Essen, , Germany

Askepios Klinik Altona-Abteilung Hamatologie und Internistische Onkologie

Hamburg, , Germany

Universitätsklinikum Heidelberg - Medizinische Klinik und Poliklinik V

Heidelberg, , Germany

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

Jena, , Germany

Universitätsklinikum Leipzig - Medizinische Klinik und Poliklinik II

Leipzig, , Germany

Universitätsklinikum Münster - Medizinische Klinik und Poliklinik A

Münster, , Germany

Universitätsklinikum Tübingen - Medizinische Klinik und Poliklinik - Abteilung II

Tübingen, , Germany

Universitätsklinikum Ulm - Klinik fur Innere Medizin III

Ulm, , Germany

Universitätsklinikum Würzburg - Medizinische Klinik und Poliklinik II

Würzburg, , Germany

University of Athens - Alexandra Hospital

Athens, , Greece

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

Bologna, , Italy

AO Universitaria San Martino - hematooncology

Genova, , Italy

Fondazione "G. Pascale" - Hematology

Napoli, , Italy

Ospedale San Luigi AO Luigi Gonzaga - Hematology

Orbassano, , Italy

Universita degli Studi di Padova - Clinical & Experimental Medicine

Padua, , Italy

Ospedale Guglielmo da Saliceto - hematooncology

Piacenza, , Italy

Unità di Ematologia Arcispedale S. Maria Nuova - Haematology

Reggio Emilia, , Italy

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

Roma, , Italy

A.O.U. San Giovanni Battista - Hematology

Torino, , Italy

VUMC - Hematology

Amsterdam, , Netherlands

Erasmus Medical Center - Hematology

Rotterdam, , Netherlands

University Medical Center - Hematology

Utrecht, , Netherlands

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

Moscow, , Russia

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

Moscow, , Russia

Russian Research Institute of Hematology and Blood Transfusion - Hematology

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

Hospital Germans Trias i Pujol - Hematology

Badalona, , Spain

Hospital Clinic i Provincial de Barcelona - Hematology

Barcelona, , Spain

Hospital de Donostia - Hematology

Guipúzcoa, , Spain

Hospital de La Princesa - Hematology

Madrid, , Spain

Hospital 12 de Octubre - Hematology

Madrid, , Spain

Hospital de Salamanca - Hematology

Salamanca, , Spain

Hospital Universitario Marqués de Valdecilla - Hematology

Santander, , Spain

Hospital La Fe - Hematology

Valencia, , Spain

Sahlgrenska Hospital, University of Goteborg - Hematology

Gothenburg, , Sweden

Karolinska University Hospital Huddinge - Center of hematology

Stockholm, , Sweden

Karolinska University Hospital-medicine

Stockholm, , Sweden

Karolinska University Hospital Solna- medicine

Stockholm, , Sweden

Overlakare Medocomcentrum - Hematology

Uppsala, , Sweden

Inselspital, Institut für Medizinische Onkologie

Bern, , Switzerland

Hôpitaux Universitaire de Genève - Oncologie

Geneva, , Switzerland

Klinik und Poliklinik für Onkologie - UniversitätsSpital Zürich

Zurich, , Switzerland

Royal Bournemouth Hospital - Haematology

Bournemouth, , United Kingdom

St James's University Hospital - Haematology

Leeds, , United Kingdom

St Bartholomew's Hospital - Medical Oncology

London, , United Kingdom

King's College Hospital - Haematology Clinical Trials

London, , United Kingdom

Freeman Hospital - Northern Centre for Cancer Care

Newcastle upon Tyne, , United Kingdom

Nottingham City Hospital - Centre for Clinical Haematology

Nottingham, , United Kingdom

Derriford Hospital - Haematology

Plymouth, , United Kingdom

Royal hallamshire Hospital - Haematology

Sheffield, , United Kingdom

Royal Marsden NHS Foundation Trust - Haematology

Surrey, , United Kingdom

Royal Wolverhampton Hospitals Trust - Research and Development

Wolverhampton, , United Kingdom

Countries

Australia; Belgium; Canada; Czechia; Denmark; France; Germany; Greece; Italy; Netherlands; Russia; Spain; Sweden; Switzerland; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 27173785 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24007748 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25403264 (View on PubMed)

Other Identifiers

2010-023343-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-4047-MM-003/C

Identifier Type: -

Identifier Source: org_study_id