Lenalidomide vs Placebo Maintenance Therapy Following Melphalan Prednisone Velcade® Induction Therapy in NDMM
- Registration Number
- NCT02112175
- Lead Sponsor
- Celgene
- Brief Summary
The purpose of this study is to compare the safety and efficacy of Lenalidomide versus Placebo maintenance following melphalan, prednisone and velcade induction therapy in newly diagnosed multiple myeloma.
After the study is unblinded, subjects in treatment Arm A (Len 10 mg) will remain on study therapy at the Investigator's discretion and subjects in treatment Arm B (placebo), will be discontinued from study treatment. Subjects who discontinued from study treatment for any reason will enter the LTFU Phase.
- Detailed Description
The planned total number of evaluable subjects for PFS was approximately 351 (234 in the lenalidomide treatment arm; 117 in the placebo treatment arm) and the study will be conducted in European countries. However, due to the significant enrollment challenges and the changes in the NDMM treatment practices in subjects who are not eligible for transplant, such as the recent approval of Revlimid in NDMM setting, the DMC recommended to close study enrollment. Study enrollment was closed on 12 October 2015.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 46
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
Related to initial diagnosis and prior Melphalan Prednisone Velcade (MPV) induction therapy
-
Previously untreated and symptomatic multiple myeloma.
-
All 3 criteria (Durie, 2003) and at least one of the Creatinine Renal insufficiency Anemia lytic Bone lesions or osteoporosis criteria must be met.
-
Measurable disease by protein electrophoresis analyses.
-
All subjects must be treated with a minimum of 6 and a maximum of 9 cycles of MPV induction regimen, and must have achieved at least Partial Response as best overall response and maintained at Melphalan Prednisone Velcade discontinuation. If a subject achieves Complete Response prior to at least 6 cycles, the subject will be eligible, but a minimum of 6 cycles must be administered otherwise.
-
Subjects must not have received any prior anti-myeloma chemotherapy or any investigational agent except 6-9 cycles of induction therapy with Melphalan Prednisone Velcade.
-
Subjects must have cytogenetic (17 p deletion, and 4;14 translocation), β-2 microglobulin and serum albumin (International Staging System) results from their initial diagnosis available at the time of screening.
Related to the subject
-
Must understand and voluntarily sign the informed consent document prior to the conduct of any study related assessments/procedures,
-
Age ≥ 65 years: if < 65 years of age, the subject must be non eligible for stem cell transplantation,
-
Eastern Cooperative Oncology Group performance status score ≤ 2,
-
Able to adhere to the study visit schedules and other protocol requirements,
-
Females of Childbearing Potential must:
- Have two negative pregnancy tests as verified by the study doctor prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy. This applies even if the subject practices true abstinence2 from heterosexual contact.
- Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting Investigational Product, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.
-
Male Subjects must:
- Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female or childbearing potential while participating in the study, during dose interruptions and for at least 28 days following Investigational Product discontinuation, even if he has undergone a successful vasectomy.
- Agree to not donate semen during Investigational Product therapy and for 28 days after end of study therapy.
-
All subjects must:
- Have an understanding that the study medication could have a potential teratogenic risk.
- Agree to abstain from donating blood while taking Investigational Product therapy and following discontinuation of Investigational Product therapy.
- Agree not to share study medication with another person.
- All female of childbearing potential and male subjects must be counseled about pregnancy precautions and risks of fetal exposure.
-
The presence of any of the following will exclude the subject from the study enrollment:
-
Previous treatment with anti-myeloma therapy other than the required 6-9 cycles of Melphalan Prednisone Velcade induction therapy (does not include local radiotherapy, bisphosphonates, or a single short course of steroid [ie, less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of randomization]).
-
Subjects who didn't achieve Partial Response or better after getting at least 6 cycles of Melphalan Prednisone Velcade and at the end of Melphalan Prednisone Velcade whatever the overall response are not eligible.
-
Prior therapy with immunomodulating or immunosuppressive agents, or epigenetic or desoxyribonucleic acid modulating agents. Subjects who received investigational agents are also excluded.
-
Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
-
Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
-
Pregnant or lactating females.
-
Any of the following laboratory abnormalities:
Absolute neutrophil count < 1,000/L (1.0 x 10*9/L) Untransfused platelet count < 50,000 cells/L (50 x 10*9/L) Serum glutamic oxaloacetic transaminase/alanine aminotransferase or serum glutamic pyruvic transaminase/alanine aminotransferase > 3.0 x upper limit of normal Serum bilirubin levels > 1.5 x upper limit of normal
-
Renal insufficiency (creatinine clearance < 30 mL/min by Cockcroft-Gault method) or actual creatinine clearance result, or renal failure requiring hemodialysis or peritoneal dialysis.
-
Prior history of malignancies including skin cancer, other than multiple myeloma.
-
Prior history of deep venous thrombosis or pulmonary embolus within 3 years of randomization.
-
Subjects who are unable or unwilling to undergo anti-thrombotic therapy.
-
Peripheral neuropathy of > Grade 2 severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.
-
Known Human Immunodeficiency Virus positivity or active infectious hepatitis, type A, B, or C.
-
Primary amyloidosis (immunoglobulin light chain) and myeloma complicated by amyloidosis.
-
Prior allogeneic or autologous stem cell transplantation.
-
Significant active cardiac disease within the previous 6 months including:
New York Heart Association class II-IV congestive heart failure Unstable angina or angina requiring surgical or medical intervention Myocardial infarction
-
Any condition that confounds the ability to interpret data from the study.
-
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Lenalidomide Lenalidomide Treatment Arm A: lenalidomide 10 mg/day orally from Days 1 to 21; given in 28-day cycles for up to disease progression.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Approximately 6 years Is defined as the time from the date of randomization to the date of death due to any cause.
- Secondary Outcome Measures
Name Time Method Safety; Adverse Events (AE) [type, frequency, and severity of AEs, and relationship of AEs to investigational product (IP) SAEs, laboratory abnormalities, hospitalizations, and SPMs Approximately 6 years An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study.
Trial Locations
- Locations (73)
CHRU Hopital Claude Huriez
🇫🇷Lile Cedax, France
Hopital Saint Louis
🇫🇷Paris, France
CH Argenteuil Victor DupouyHematologie
🇫🇷Argenteuil, France
Centre Hospitalier de Jolimont-Lobbes
🇧🇪La Louvière-(Haine St-Paul), Belgium
Centre Hospitalier de Blois
🇫🇷Blois Cedex, France
CH La Source Onco-Hèmatologie
🇫🇷Orleans, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Bénite, France
Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour
🇧🇪Baudour, Belgium
CHU de Nimes
🇫🇷Nimes Cedex 9, France
CH - Hôpital Dupuytren
🇫🇷Limoges Cedex 1, France
Centre Hospitalier Regional Metz-Thionville Hopital de Mercy
🇫🇷Metz Cedex 03, France
Clinica Universitaria de Navarra
🇪🇸Pamplona, Spain
Hospital Central de Asturias
🇪🇸Oviedo, Spain
Ospedale Sant'Eugenio
🇮🇹Rome, Italy
CHRU Hopital sud Medecine Interne
🇫🇷Rennes cedex 02, France
Centre Hospitalier Yves Le Foll
🇫🇷St-Brieuc cedex 1, France
Policlinico Umberto I
🇮🇹Roma, Italy
Hospital La Princesa
🇪🇸Madrid, Spain
Ospedale Civile di Piacenza
🇮🇹Piacenza, Italy
Hospital virgen de la Arrixaca
🇪🇸El Palmar (murcia), Spain
Hospital Costa del Sol
🇪🇸Marbella, Spain
A.O. Universitaria Fondazione Macchi
🇮🇹Varese, Italy
Hospital Sant Pau
🇪🇸Barcelona, Spain
IRCCS Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Italy
Spedali Civili Brescia
🇮🇹Brescia, Italy
Clinica Ematologica, A.O.U. San Martino di Genova
🇮🇹Genova, Italy
Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale
🇮🇹Napoli, Campania, Italy
Policlinico San Matteo Universita Di Pavia
🇮🇹Pavia 2, Italy
Polyclinique Bordeaux Nord Aquitaine
🇫🇷Bordeaux, France
CHU de la cote de Nacre
🇫🇷Caen, France
Hopital A. MorvanHematologie
🇫🇷Brest cedex, France
Chu Estaing
🇫🇷Clermont Ferrand, France
Groupe Hospitalier Pitié- Salpétrière
🇫🇷Paris, France
CH Perpignan - Hopital Saint-Jean
🇫🇷Perpignan, France
Centre Hospitalier de la Region d'Annecy
🇫🇷Pringy, France
CHRU Hôpital de Hautepierre
🇫🇷Strasbourg, France
AZ-VUB
🇧🇪Brussels, Belgium
Grand Hopital de Charleroi
🇧🇪Charleroi, Belgium
Universitair Ziehenhuis Antwerpen
🇧🇪Edegem, Belgium
AZ Nikolaas
🇧🇪Sint-Niklaas, Belgium
Cliniques Universitaires UCL de Mont-Godine
🇧🇪Yvoir, Belgium
Hopital Jean Minjoz Hematologie
🇫🇷Besancon, France
Centre Hospitalier de la cote basque
🇫🇷Bayonne, France
Hopital de Fleyriat
🇫🇷Bourg en Bresse cedex, France
CHRU - Hotel Dieu
🇫🇷Clemont-Ferrand Cedex, France
CHD Vendee
🇫🇷La Roche Sur Yon, France
CH Hematologie
🇫🇷Le Chesnay Cedex, France
Hopital Henri Mondor
🇫🇷Creteil, France
Centre Hospitalier
🇫🇷Dunkerque, France
Centre Hospitalier Sud Francilien - Site Gilles de Corbeil
🇫🇷Corbeil Essonnes, France
Kremlin Bicetre
🇫🇷Le Kremlin bicetre CDX, France
Centre Hospitalier Medecine interne
🇫🇷Le Mans cedex, France
Centre Jean BernardOnco-Hematologie
🇫🇷Le Mans, France
Institut Universitaire du Cancer IUCT - Oncopole
🇫🇷Toulouse Cedex, France
Laiko General Hospital of Athens
🇬🇷Athens, Greece
Hopital civil
🇫🇷Strasbourg, France
CHRU Hopital BretonneauOnco-hematologie
🇫🇷Tours cedex, France
CHRU Hôpitaux de Brabois
🇫🇷Vandoeuvre, France
Alexandra General Hospital of Athens
🇬🇷Athens, Greece
University of Patras
🇬🇷Patras, Greece
Theagenio Anticancer Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Ospedale Ferrarotto
🇮🇹Catania, Italy
Policlinico Sant'Orsola-Malpighi
🇮🇹Bologna, Italy
U.O. di Ematologia e Trapianto di Midollo Osseo
🇮🇹Milano, Italy
Unità Operativa di Oncoematologia, Ospedale di Matera
🇮🇹Matera, Italy
Ematologia ed Immunologia, Azienda Ospedaliera Vito Fazzi di Lecce
🇮🇹Lecce, Italy
Dipartimento Medicina ed Oncologia Sperimentale - Divisione Universitaria di Ematologia Azienda Ospe
🇮🇹Torino, Italy
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
Ospedale Umberto I
🇮🇹Torrette Di Ancona, Italy
Hospital Clinic Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Virgenes de las Nieves
🇪🇸Granada, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Complejo Hospitalario de Santiago
🇪🇸Santiago de Compostela, Spain