Clinical trial NCT01324947: Study to Evaluate the Safety and Efficacy of Pomalidomide Monotherapy in Subjects With Refractory or Relapsed Refractory Multiple Myeloma
Official title: Open-label, Multi-center, Single Arm Study For The Safety And Efficacy Of Pomalidomide Monotherapy For Subjects With Refractory Or Relapsed And Refractory Multiple Myeloma. A Companion Study For Clinical Trial CC-4047-MM003
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2011-03-29
Enrollment: 74
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 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.


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.

Primary outcomes:
measure: Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria Based on Investigator Assessment
timeFrame: 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:
measure: Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria Based on Investigator Assessment
timeFrame: 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.
measure: Number of Participants With Adverse Events and Type of Adverse Events
timeFrame: 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.
measure: Kaplan Meier Estimates for Progression Free Survival (PFS) by Investigator Based on IMWG
timeFrame: From randomization through the follow-up phase; Maximum duration of follow-up for PFS was 90.3 weeks.
measure: Kaplan-Meier Estimate for Time to Progression (TTP) Based on Investigator Assessment Using IMWG Criteria
timeFrame: 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.
measure: Kaplan-Meier Estimate Duration of Response Based on Investigator Assessment Using IMWG Criteria
timeFrame: 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.
measure: Kaplan-Meier Estimate for Overall Survival
timeFrame: From randomization through the follow-up phase; Maximum time on follow-up was 141.1 weeks.
measure: Time to Response Based on IMWG and Assessed by the Investigator
timeFrame: From randomization through the follow-up phase; up to the data-cut off of 31 July 2014; Maximum time to response was 23.1 weeks
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital - SA Pathology Haematology
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital - Haematology
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital - Institute of Haematology
city: East Melbourne
country: Australia
facility: Peter McCallum Cancer Institute - Directorate of Cancer Medicine
city: Frankston
country: Australia
facility: Frankston Hospital-Peninsula Health - Oncology Day Unit
city: Melbourne
country: Australia
facility: The Alfred Hospital - Malignant Haematology & Stem Cell Transplantation
city: Waratah
country: Australia
facility: Calvary Mater Newcastle - Haematology
city: Wodonga
country: Australia
facility: Border Medical Oncology
city: Wollongong
country: Australia
facility: Wollongong Hospital - Haematology
city: Gent
country: Belgium
facility: UZ Gent - Hematology
city: Leuven
country: Belgium
facility: University Hospital Leuven - Hematology
city: Yvoir
country: Belgium
facility: Cliniques Universitaires ULC de Mont-Godinne - Hematology
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency, Vancouver Centre
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital, University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Prague
country: Czechia
facility: Charles University Hospital - Internal Medicine
city: Aalborg
country: Denmark
facility: Aalborg Sygemus - Haematology
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital - Hematology
city: Angers
country: France
facility: CHU Angers - Service des maladies du sang
city: Bayonne
country: France
facility: Centre Hospitalier de la côte basque - Hematologie
city: La Roche
country: France
facility: Centre Hospitalier Départemental Vendée - Onco-hematologie
city: Lille
country: France
facility: CHRU de Lille - Service des maladies du sang
city: Marseille
country: France
facility: Institut Paoli Calmette - Hematology 1
city: Nantes
country: France
facility: CHU Hôtel-Dieu - Hematologie
city: Paris
country: France
facility: Hôpital Saint Louis - Immuno-hematologie
city: Paris
country: France
facility: CHU Saint Antoine - Service des maladies du sang
city: Pessac
country: France
facility: CHRU - Hôpital du Haut Lévêque - Centre François Magendie Service des maladies du sang
city: Pierre-Benite
country: France
facility: Centre Hospitalier Lyon sud - Hematologie
city: Toulouse
country: France
facility: CHRU Hôpital Purpan - Hematologie
city: Tours
country: France
facility: Hôpital Bretonneau - Hématologie & Thérapie cellulaire
city: Vandoeuvre-les-Nancy
country: France
facility: CHU Nancy - Hematologie
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus-Medizinische Klinik und Poliklinik I
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Hämatologie Westdeutsches Tumorzentrum
city: Hamburg
country: Germany
facility: Askepios Klinik Altona-Abteilung Hamatologie und Internistische Onkologie
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg - Medizinische Klinik und Poliklinik V
city: Jena
country: Germany
facility: Universitätsklinikum Jena - Klinik fur Innere Medizin II-Hamatologie/Onkologie
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig - Medizinische Klinik und Poliklinik II
city: Münster
country: Germany
facility: Universitätsklinikum Münster - Medizinische Klinik und Poliklinik A
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen - Medizinische Klinik und Poliklinik - Abteilung II
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm - Klinik fur Innere Medizin III
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg - Medizinische Klinik und Poliklinik II
city: Athens
country: Greece
facility: University of Athens - Alexandra Hospital
city: Bologna
country: Italy
facility: Università degli Studi di Bologna - Policlinico S. Orsola - Hematology
city: Genova
country: Italy
facility: AO Universitaria San Martino - hematooncology
city: Napoli
country: Italy
facility: Fondazione "G. Pascale" - Hematology
city: Orbassano
country: Italy
facility: Ospedale San Luigi AO Luigi Gonzaga - Hematology
city: Padova
country: Italy
facility: Universita degli Studi di Padova - Clinical & Experimental Medicine
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto - hematooncology
city: Reggio Emilia
country: Italy
facility: Unità di Ematologia Arcispedale S. Maria Nuova - Haematology
city: Roma
country: Italy
facility: Policlinico Umberto I, Università "La Sapienza" di Roma - Hematology
city: Torino
country: Italy
facility: A.O.U. San Giovanni Battista - Hematology
city: Amsterdam
country: Netherlands
facility: VUMC - Hematology
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center - Hematology
city: Utrecht
country: Netherlands
facility: University Medical Center - Hematology
city: Moscow
country: Russian Federation
facility: Hematological Research Center under the Russian Academy of Medical Sciences - Hematology & BMT
city: Moscow
country: Russian Federation
facility: Moscow State Medical Institution Municipal Clinical Hospital n.a. S.P. Botkin - Hematology
city: St. Petersburg
country: Russian Federation
facility: Russian Research Institute of Hematology and Blood Transfusion - Hematology
city: St. Petersburg
country: Russian Federation
facility: State Higher Educational Institution St. Petersburg State Medical University - Onco-hematology
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol - Hematology
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona - Hematology
city: Guipúzcoa
country: Spain
facility: Hospital de Donostia - Hematology
city: Madrid
country: Spain
facility: Hospital de La Princesa - Hematology
city: Madrid
country: Spain
facility: Hospital 12 de Octubre - Hematology
city: Salamanca
country: Spain
facility: Hospital de Salamanca - Hematology
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla - Hematology
city: Valencia
country: Spain
facility: Hospital La Fe - Hematology
city: Goteborg
country: Sweden
facility: Sahlgrenska Hospital, University of Goteborg - Hematology
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge - Center of hematology
city: Stockholm
country: Sweden
facility: Karolinska University Hospital-medicine
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Solna- medicine
city: Uppsala
country: Sweden
facility: Overlakare Medocomcentrum - Hematology
city: Bern
country: Switzerland
facility: Inselspital, Institut für Medizinische Onkologie
city: Genève
country: Switzerland
facility: Hôpitaux Universitaire de Genève - Oncologie
city: Zürich
country: Switzerland
facility: Klinik und Poliklinik für Onkologie - UniversitätsSpital Zürich
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital - Haematology
city: Leeds
country: United Kingdom
facility: St James's University Hospital - Haematology
city: London
country: United Kingdom
facility: St Bartholomew's Hospital - Medical Oncology
city: London
country: United Kingdom
facility: King's College Hospital - Haematology Clinical Trials
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital - Northern Centre for Cancer Care
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital - Centre for Clinical Haematology
city: Plymouth
country: United Kingdom
facility: Derriford Hospital - Haematology
city: Sheffield
country: United Kingdom
facility: Royal hallamshire Hospital - Haematology
city: Surrey
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Haematology
city: Wolverhampton
country: United Kingdom
facility: Royal Wolverhampton Hospitals Trust - Research and Development
Study officials:
affiliation: Celgene Corporation
name: Mohamed Zaki, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.