A Multicenter, Single-Arm, Open-Label Expanded Access Program for Lenalidomide Plus Dexamethasone in Previously Treated Subjects With Multiple Myeloma

NCT00478777 | Completed Phase 3 Results DMC

• 2 other identifiers: CC-5013-MM-0192006-004532-73
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 48

Brief Summary

This was a multicenter, open-label, single-arm phase 3B study of the combination lenalidomide plus pulse high-dose dexamethasone. This study (CC-5013-MM-019) was set up and executed primarily as an expanded access program in Germany. Screening procedures were to take place within 28 days prior to Cycle 1 Day 1 (baseline) with the exception of hematology assessments that were to be performed within 14 days prior to Cycle 1 Day 1. Randomization, blinding, and stratification were not applied in this open-label single-arm study. Eligible subjects given open-label treatment and received treatment with lenalidomide plus high-dose dexamethasone in 28-day cycles. Lenalidomide (hard capsules) was to be administered orally (PO) at a dose of 25 mg daily (QD) for the first 21 days of each 28-day cycle. According to the protocol, accrual of subjects to the study was to be terminated within 2 months of commercial availability of lenalidomide for this indication in Germany. Upon discontinuation from study, minimal information was collected in order to identify when disease progressed.

Conditions

Relapsed or Refractory Multiple Myeloma

Keywords

CC-5013; Revlimid; Lenalidomide; Celgene; Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Kaplan Meier Estimate for Time to Disease Progression

  Time to disease progression (TTP) was based on the European Group for Blood and Marrow Transplantation (EBMT) myeloma response determination criteria developed by Bladé (Bladé, 1998). TTP is a Kaplan Meier estimate of the time from randomization to the first documentation of progressive disease. Progressive disease based on increasing monoclonal paraprotein levels require a confirmatory value one week apart. Disease progression can also be based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

  up to 827 days

Secondary Outcomes (3)

• Participant's Best Overall Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Criteria

  Up to 827 days

• Participants With Treatment-emergent Adverse Experiences (TEAEs)

  up to 8 months

• Time to Partial Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Determination Criteria

  up to 827 days

Study Arms (1)

lenalidomide plus dexamethasone

EXPERIMENTAL

Lenalidomide administered orally, 25 mg daily (QD) for the first 21 days of each 28-day cycle. Pulse dexamethasone administered orally, 40 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle during Cycles 1 to 4 (approximately months 1-4). Beginning with Cycle 5 (approximately month 5), dexamethasone was to be reduced to 40 mg QD for Days 1-4 of each 28 day-cycle.

Drug: Lenalidomide; Drug: dexamethasone

Interventions

Lenalidomide DRUG

Oral lenalidomide at a dose of 25 mg daily for 21 days every 28 days. Treatment as tolerated until disease progression.

Also known as: Revlimid®

lenalidomide plus dexamethasone

dexamethasone DRUG

Oral pulse dexamethasone at a dose of 40 mg daily on days 1-4, 9-12, and 17-20 for each 28-day-cycle for cycles 1 through 4 (approximately months 1-4). Beginning cycle 5 (approximately month 5) dexamethasone is reduced to 40 mg daily for days 1-4 every 28 days.

lenalidomide plus dexamethasone

Eligibility Criteria

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

You may qualify if:

• Must understand and voluntarily sign an informed consent form.
• Must be ≥18 years of age at the time of signing the informed consent form.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Must be diagnosed with multiple myeloma that is progressing after at least 2 cycles of anti-myeloma treatment or that has relapsed with progressive disease after treatment.
• Subjects may have been previously treated with thalidomide and/or radiation therapy. In addition, radiation therapy initiated prior to or at baseline (Day 1) may be given concurrently with study therapy, provided that all other eligibility criteria are satisfied.
• Subjects must discontinue all anti-myeloma drug or non-drug therapy prior to the first dose of study drug with the exception of radiation therapy initiated prior to or at baseline (Day 1).
• Measurable levels of myeloma paraprotein in serum (\>0.5 g/dL) or urine (\>0.2 g excreted in a 24-hour collection sample).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.

You may not qualify if:

• The presence of any of the following will exclude a subject from study enrollment:
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or lactating females.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) \<1,000 cells/mm\^3 (1.0 x 10\^9/L)
• Platelet count \<75,000/mm\^3 (75 x 109/L) for subjects in whom \<50% of the bone marrow nucleated cells are plasma cells.
• Platelet count \<30,000/mm\^3 (30x10\^9/L) for subjects in whom ≥50% of bone marrow nucleated cells are plasma cells.
• Serum creatinine \>2.5 mg/dL (221 µmol/L)
• Serum SGOT/AST or SGPT/ALT \>3.0 x upper limit of normal (ULN)
• Serum total bilirubin \>2.0 mg/dL (34 µmol/L)
• Prior history of malignancies other than multiple myeloma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for ≥1 year.
• Prior history of stroke and/or thromboembolic event
• Known hypersensitivity to thalidomide or dexamethasone.
• Prior history of uncontrollable side effects to dexamethasone therapy.

Sponsors & Collaborators

• Celgene Corporation: lead

Study Sites (48)

Medizinische Klinik und Poliklinik II der Charité Universitätsmedizin Berlin Campus Mitte

Berlin, 10117, Germany

Location

Poliklinik I, Hämatologie/ Onkologie, Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Johanniter-Krankenhaus Bonn Friedrich-Wilhelm-Stift gGmbH

Bonn, 53113, Germany

Location

Medizinische Klinik Städtisches Klinikum Braunschweig gGmbH

Braunschweig, D-38114, Germany

Location

Interne Klinik Dr. Argirov, Schön-Kliniken

Burg, 82335, Germany

Location

Klinik für Innere Medizin III Klinikum Chemnitz gGmbH

Chemnitz, 09113, Germany

Location

Ärzte f. Innere Medizin Gemeinschaftspraxis f. Hämatologie u. Onkologie

Cologne, 50677, Germany

Location

Klinik f. Innere Medizin, Klinikum der Universität zu Köln

Cologne, 50924, Germany

Location

Medizinische Klinik und Poliklinik, Uniklinikum Dresden

Dresden, 01307, Germany

Location

Universitaetsklinikum Dusseldorf Klinik fuer Haematologie

Düsseldorf, 40225, Germany

Location

Direktor der Klinik f. Hämatologie, Universitätsklinikum Essen

Essen, 45122, Germany

Location

Universitätsklinikum EssenInnere Klinik und Poliklinik

Essen, 45122, Germany

Location

Klinik für Innere Medizin, Klinikum Frankfurt (Oder) GmbH

Frankfurt (Oder), 15236, Germany

Location

Medizinische Klinik II (ZIM),Hämatologie / Onkologie Uniklinik Frankfurt

Frankfurt am Main, 60590, Germany

Location

Abt. Innere Medizin I , Hämatologie / Onkologie, Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum GöttingenHamatologie und Onkologie

Göttingen, 37075, Germany

Location

Interdisziplinäre Klinik und Poliklinik für Stammzellentransplantation Universitätsklinik Hamburg - Eppendorf

Hamburg, 20246, Germany

Location

II. Medizinische Abteilung, Asklepios Klinikum Altona

Hamburg, 22763, Germany

Location

Abt. Hämatologie, Hämatologie und Onkologie, Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Medizinische Klinik und Poliklinik V Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Klinik für Innere Medizin II Hämatologie / Onkologie Universitätsklinikum Jena

Jena, 07740, Germany

Location

EPS - Early Phase Solutions GmbH

Jena, 07743, Germany

Location

Hämatologie / Onkologie / Infektionskrankheiten, Palliativmedizin Städtisches Klinikum Karlsruhe

Karlsruhe, 76135, Germany

Location

2. Med. Klinik , Sektion f. Stammzell- + Immuntherapie Universitätsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

Institut für Versorgungsforschung in der Onkologie Praxisklinik für Hämatologie und Onkologie

Koblenz, 56068, Germany

Location

Medizinische Klinik und Poliklinik II Abt. Hämatologie / Onkologie, Universitätsklinikum Leipzig AÖR

Leipzig, 04103, Germany

Location

III. Med. Klinik, Johannes Gutenberg Universität

Mainz, 55101, Germany

Location

Klinikum Mannheim der Universität Heidelberg

Mannheim, 68305, Germany

Location

Hämatologisch-Onkologisches Institut für medizinische Service Leistungen

Mönchengladbach, 41239, Germany

Location

Medizinische Klinik III Klinikum der Universität München-Großhadern

München, 81377, Germany

Location

Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster

Münster, 48129, Germany

Location

Fachärzte für Innere Medizin Hämatologie und Onkologie Gemeinschaftspraxis

Münster, 48149, Germany

Location

Onkologie Praxis Oldenburg

Oldenburg, 26121, Germany

Location

Abt. Onkologie/ Hämatologie, Klinikum Oldenburg

Oldenburg, 26133, Germany

Location

Abteilung Hämatologie und Onkologie, Hämatologie und Onkologie, Medizinische Klinik, Klinikum Ernst v. Bergmann

Potsdam, 14467, Germany

Location

Klinikum der Universität Regensburg

Regensburg, 93053, Germany

Location

Abteilung Hämatologie und Onkologie, Medizinische Fakultät der Universität Rostock

Rostock, 18057, Germany

Location

Caritasklinik St. Theresia

Saarbrücken, 66113, Germany

Location

ms² Medizinische Statistik Saarbrücken

Saarbrücken, D-66113, Germany

Location

Med. Klinik III , St. Marienkrankenhaus Siegen

Siegen, 57072, Germany

Location

Zentrum für Innere Medizin II Robert- Bosch-Krankenhaus GmBH

Stuttgart, D -70376, Germany

Location

Krankenanstalt Mutterhaus der Borromäerinnen

Trier, 54290, Germany

Location

Abt. II Hämatologie, Onkologie und Immunologie Medizinische Klinik Abt.II

Tübingen, 72076, Germany

Location

Medizinische Universitätsklinik

Ulm, 89081, Germany

Location

Med. Klinik 1, Helios Klinikum Wuppertal

Wuppertal, 42283, Germany

Location

Praxis Dres. Maintz & GroschekHämatologie / Onkologie

Würselen, 52146, Germany

Location

Med. Klinik u. Poliklinik IIKlinikum der Universität Würzburg

Würzburg, 97080, Germany

Location

Hämatologisch-onkologische Praxis

Würzburg, D-97070, Germany

Location

Related Publications (1)

• Weisel, Katja Christina, et. al. Speed of Response with Lenalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma: First Results of the MM-019 Compassionate Use Protocol. 14th Congress of the European Hematology Association, June 2009. Haematologica 2009; 94(Suppl 2):160 abs.0397. http://www.eventure-online.com/eventure/publicAbstractView.do?id=101710&congressId=2432

  RESULT

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Axel Glasmacher, MD

  University of Bonn

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: May 23, 2007
• First Posted: May 25, 2007
• Study Start: March 1, 2007
• Primary Completion: November 1, 2007
• Study Completion: August 1, 2009
• Last Updated: November 3, 2011
• Results First Posted: November 3, 2011

Record last verified: 2011-09

Locations

DE (48)