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 (NIMBUS)
Multiple Myeloma
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring 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
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
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
- Subjects who received any of the following within the last 14 days of initiation of study treatment: 1) Plasmapheresis, 2) Major surgery, 3) Radiation therapy, 4) Use of any anti-myeloma drug therapy
- Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment
- Subjects with conditions requiring chronic steroid or immunosuppressive treatment
- Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide
- Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form
- Pregnant or breastfeeding females
- Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis A, B, or C
Sites / Locations
- Mayo Clinic
- Royal Adelaide Hospital
- Peter MacCallum Cancer Institute
- Frankston Hospital
- Princess Alexandra Hospital
- Royal Prince Alfred Hospital
- Alfred hospital
- Sir Charles Gairdner Hospital
- Calvary Mater Hospital
- Border Medical Oncology
- Wollongong Hospital
- UZ Gent
- UZ Leuven
- CHU UCL Mont-Godinne-Dinant asbl
- Tom Baker Cancer Center
- Cross Cancer Institute
- British Columbia Cancer Agency
- James Cancer Hospital
- Juravinski Cancer Centre
- London Health Sciences Centre
- University Health Network
- Maisonneuve Rosemont
- Royal Victoria Hospital McGill Department of Oncology(RVH)
- Sir Mortimer B. Davis - Jewish Genl
- Charles University General Hospital
- Hæmatologisk afd. B Aalborg Sygehus Syd
- Aarhus University Hospital
- Odense Universitetshospital
- Vejle Hospital
- CHU d'Angers
- Centre Hospitalier de la cote basque
- Centre Hospitalier Departemental
- CHRU de Lille FR
- Institut Paoli-Calmettes
- CHRU Nantes
- Hopital Saint-Louis
- CHU Hôpital St-Antoine
- CHRU - Hopital du Haut Leveque
- Centre Hospitalier Lyon Sud
- Hopital Bretonneau
- Hopital Purpan
- CHU Nancy
- Universitatsklinikum Carl Gustav Carus
- Universitatsklinikum Essen
- Askepios Klinik St. Georg
- Universitatsklinikum Heidelberg
- Universitatsklinikum Jena
- Universitatsklinikum Leipzig
- University of Tubingen
- Universitatsklinikum Ulm
- Universitatsklinikum Wurzburg
- Alexandra General Hospital of Athens
- Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
- Clinica Ematologica- A.O.U. San Martino
- Oncoematologia, Istituto Nazionale Tumori Fondazione G. Pascale
- AOU San Luigi Gonzaga
- Universita degli Studi di Padova
- Hospital Clinic
- Servizio di Ematologia, A.O. - Arcispedale S.Maria Nuova
- Univerita La Sapienza Dipartimento di Biotecnologie Cellulari ed Ematologia
- Azienda Ospedaliera San Giovanni Battista
- VU University Medical Center
- Erasmus Medical Center
- University Medical Center Utrecht
- State Institution Hematological Research, Centre of Russian Academy of Medical Science
- State Institution Moscow Regional Research Clinical Institute
- State Educational Institution, Saint Petersburg State Medical University
- St. Petersburg Research Institute of Hematology and Blood Transfusion
- Hospital Universitari Germans Trias i Pujol
- Hospital Clinic Provincial de Barcelona
- Hospital de La Princesa
- Hospital 12 de Octubre
- Hospital Universitario de Salamanca
- Hospital Donostia
- Hospital Universitario Marques de Valdecilla
- Hospital de la Fe
- Department of Hematology Hematology Centre
- University Hospital in Lund
- Karolinska University Hospital Huddinge
- Karolinska University Hospital
- Overlakare Medocomcentrum, hematologi
- Medizinische Universitatsklinik
- Hopitaux Universitaires de Geneve-HUG
- UniversitatSspital Zurich
- Royal Bournemouth Hospital
- St James's University Hospital
- St.Bartholomew's Hospital
- King's College Hospital
- Freeman Hospital
- Nottingham City Hospital
- Derriford Hospital
- Royal Hallamshire HospitalSheffield Teaching Hospitals NHS Trust
- The Royal Marsden Hospital
- The Royal Wolverhampton Hospital NHS Trust
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Pomalidomide + Low-Dose Dexamethasone
High-Dose Dexamethasone
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.
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.