Lenalidomide vs Placebo Maintenance Therapy Following Melphalan Prednisone Velcade® Induction Therapy in NDMM

NCT02112175 | Completed Phase 3 DMC

• 1 other identifier: CC-5013-MM-026
• Study Type: interventional
• Target: 46
• Locations: 5 countries
• Sites: 73

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.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Lenalidomide; Revlimid; MPV; Melphalan; Prednisone; Velcade; Placebo

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Is defined as the time from the date of randomization to the date of death due to any cause.

  Approximately 6 years

Secondary Outcomes (1)

• 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

Study Arms (1)

Lenalidomide

EXPERIMENTAL

Treatment Arm A: lenalidomide 10 mg/day orally from Days 1 to 21; given in 28-day cycles for up to disease progression.

Drug: Lenalidomide

Interventions

Lenalidomide DRUG

Lenalidomide

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (73)

Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour

Baudour, 7331, Belgium

Location

AZ-VUB

Brussels, 1090, Belgium

Location

Grand Hopital de Charleroi

Charleroi, 6000, Belgium

Location

Universitair Ziehenhuis Antwerpen

Edegem, 2650, Belgium

Location

Centre Hospitalier de Jolimont-Lobbes

La Louvière-(Haine St-Paul), 7100, Belgium

Location

AZ Nikolaas

Sint-Niklaas, 9100, Belgium

Location

Cliniques Universitaires UCL de Mont-Godine

Yvoir, 5530, Belgium

Location

CH Argenteuil Victor DupouyHematologie

Argenteuil, 95100, France

Location

Centre Hospitalier de la cote basque

Bayonne, 64109, France

Location

Hopital Jean Minjoz Hematologie

Besançon, 25000, France

Location

Centre Hospitalier de Blois

Blois, 41016, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, 33300, France

Location

Hopital de Fleyriat

Bourg-en-Bresse, 01012, France

Location

Hopital A. MorvanHematologie

Brest, 29609, France

Location

CHU de la cote de Nacre

Caen, 14000, France

Location

CHRU - Hotel Dieu

Clemont-Ferrand Cedex, 63003, France

Location

Chu Estaing

Clermont-Ferrand, 63000, France

Location

Centre Hospitalier Sud Francilien - Site Gilles de Corbeil

Corbeil-Essonnes, 91106, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Centre Hospitalier

Dunkirk, 59385, France

Location

CHD Vendee

La Roche-sur-Yon, 85000, France

Location

CH Hematologie

Le Chesnay, 78157, France

Location

Kremlin Bicetre

Le Kremlin-Bicêtre, 942975, France

Location

Centre Jean BernardOnco-Hematologie

Le Mans, 72000, France

Location

Centre Hospitalier Medecine interne

Le Mans, 72037, France

Location

CHRU Hopital Claude Huriez

Lile Cedax, 59037, France

Location

CH - Hôpital Dupuytren

Limoges, 87042, France

Location

Centre Hospitalier Regional Metz-Thionville Hopital de Mercy

Metz, 57038, France

Location

CHU de Nimes

Nîmes, 30029, France

Location

CH La Source Onco-Hèmatologie

Orléans, 45000, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Groupe Hospitalier Pitié- Salpétrière

Paris, 75651, France

Location

CH Perpignan - Hopital Saint-Jean

Perpignan, 66046, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier de la Region d'Annecy

Pringy, 74374, France

Location

CHRU Hopital sud Medecine Interne

Rennes, 35056, France

Location

Centre Hospitalier Yves Le Foll

Saint-Brieuc, 22027, France

Location

Hopital civil

Strasbourg, 67091, France

Location

CHRU Hôpital de Hautepierre

Strasbourg, 67098, France

Location

Institut Universitaire du Cancer IUCT - Oncopole

Toulouse, 31059, France

Location

CHRU Hopital BretonneauOnco-hematologie

Tours, 37044, France

Location

CHRU Hôpitaux de Brabois

Vandœuvre-lès-Nancy, France

Location

Laiko General Hospital of Athens

Athens, 11527, Greece

Location

Alexandra General Hospital of Athens

Athens, 11528, Greece

Location

University of Patras

Pátrai, 26500, Greece

Location

Theagenio Anticancer Hospital of Thessaloniki

Thessaloniki, 540 07, Greece

Location

Policlinico Sant'Orsola-Malpighi

Bologna, 40138, Italy

Location

Spedali Civili Brescia

Brescia, 25123, Italy

Location

Ospedale Ferrarotto

Catania, 95124, Italy

Location

Clinica Ematologica, A.O.U. San Martino di Genova

Genova, 16132, Italy

Location

Ematologia ed Immunologia, Azienda Ospedaliera Vito Fazzi di Lecce

Lecce, 73100, Italy

Location

Unità Operativa di Oncoematologia, Ospedale di Matera

Matera, 75100, Italy

Location

U.O. di Ematologia e Trapianto di Midollo Osseo

Milan, 20132, Italy

Location

Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale

Napoli, Campania, 80131, Italy

Location

Policlinico San Matteo Universita Di Pavia

Pavia, 27100, Italy

Location

Ospedale Civile di Piacenza

Piacenza, 29100, Italy

Location

Arcispedale Santa Maria Nuova

Reggio Emilia, 42100, Italy

Location

Policlinico Umberto I

Roma, 00161, Italy

Location

Ospedale Sant'Eugenio

Rome, 00144, Italy

Location

IRCCS Casa Sollievo della Sofferenza

San Giovanni Rotondo, 71013, Italy

Location

Dipartimento Medicina ed Oncologia Sperimentale - Divisione Universitaria di Ematologia Azienda Ospe

Torino, 10126, Italy

Location

Ospedale Umberto I

Torrette Di Ancona, 60020, Italy

Location

A.O. Universitaria Fondazione Macchi

Varese, 21100, Italy

Location

Hospital Sant Pau

Barcelona, 08025, Spain

Location

Hospital Clinic Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital virgen de la Arrixaca

El Palmar (murcia), 30120, Spain

Location

Hospital Virgenes de las Nieves

Granada, 18014, Spain

Location

Hospital La Princesa

Madrid, 28006, Spain

Location

Hospital Costa del Sol

Marbella, 29603, Spain

Location

Hospital Central de Asturias

Oviedo, 33006, Spain

Location

Clinica Universitaria de Navarra

Pamplona, 31008, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Complejo Hospitalario de Santiago

Santiago de Compostela, 15706, Spain

Location

Related Publications (5)

• Ailawadhi S, Jacobus S, Sexton R, Stewart AK, Dispenzieri A, Hussein MA, Zonder JA, Crowley J, Hoering A, Barlogie B, Orlowski RZ, Rajkumar SV. Disease and outcome disparities in multiple myeloma: exploring the role of race/ethnicity in the Cooperative Group clinical trials. Blood Cancer J. 2018 Jul 6;8(7):67. doi: 10.1038/s41408-018-0102-7.

  PMID: 29980678 BACKGROUND

• Dumontet C, Hulin C, Dimopoulos MA, Belch A, Dispenzieri A, Ludwig H, Rodon P, Van Droogenbroeck J, Qiu L, Cavo M, Van de Velde A, Lahuerta JJ, Allangba O, Lee JH, Boyle E, Perrot A, Moreau P, Manier S, Attal M, Roussel M, Mohty M, Mary JY, Civet A, Costa B, Tinel A, Gaston-Mathe Y, Facon T. A predictive model for risk of early grade >/= 3 infection in patients with multiple myeloma not eligible for transplant: analysis of the FIRST trial. Leukemia. 2018 Jun;32(6):1404-1413. doi: 10.1038/s41375-018-0133-x. Epub 2018 Apr 26.

  PMID: 29784907 BACKGROUND

• Jain T, Sonbol MB, Firwana B, Kolla KR, Almader-Douglas D, Palmer J, Fonseca R. High-Dose Chemotherapy with Early Autologous Stem Cell Transplantation Compared to Standard Dose Chemotherapy or Delayed Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis. Biol Blood Marrow Transplant. 2019 Feb;25(2):239-247. doi: 10.1016/j.bbmt.2018.09.021. Epub 2018 Sep 20.

  PMID: 30244101 BACKGROUND

• Gambella M, Omede P, Spada S, Muccio VE, Gilestro M, Saraci E, Grammatico S, Larocca A, Conticello C, Bernardini A, Gamberi B, Troia R, Liberati AM, Offidani M, Rocci A, Palumbo A, Cavo M, Sonneveld P, Boccadoro M, Oliva S. Minimal residual disease by flow cytometry and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction in patients with myeloma receiving lenalidomide maintenance: A pooled analysis. Cancer. 2019 Mar 1;125(5):750-760. doi: 10.1002/cncr.31854. Epub 2018 Dec 18.

  PMID: 30561775 BACKGROUND

• Pegourie B, Karlin L, Benboubker L, Orsini-Piocelle F, Tiab M, Auger-Quittet S, Rodon P, Royer B, Leleu X, Bareau B, Cliquennois M, Fuzibet JG, Voog E, Belhadj-Merzoug K, Decaux O, Rey P, Slama B, Leyronnas C, Zarnitsky C, Boyle E, Bosson JL, Pernod G; IFM Group. Apixaban for the prevention of thromboembolism in immunomodulatory-treated myeloma patients: Myelaxat, a phase 2 pilot study. Am J Hematol. 2019 Jun;94(6):635-640. doi: 10.1002/ajh.25459. Epub 2019 Apr 1.

  PMID: 30859608 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; 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

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Amine Bensmaine, MD

  Celgene Corporation

  STUDY DIRECTOR

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: April 9, 2014
• First Posted: April 11, 2014
• Study Start: April 30, 2014
• Primary Completion: October 12, 2020
• Study Completion: October 12, 2020
• Last Updated: April 14, 2021

Record last verified: 2021-04

Locations

BE (7); ES (10); IT (17); GR (4); FR (35)