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

September 26, 2011 updated by: Celgene Corporation

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 10117
        • Medizinische Klinik und Poliklinik II der Charité Universitätsmedizin Berlin Campus Mitte
      • Bonn, Germany, 53105
        • Poliklinik I, Hämatologie/ Onkologie, Universitätsklinikum Bonn
      • Bonn, Germany, 53113
        • Johanniter-Krankenhaus Bonn Friedrich-Wilhelm-Stift gGmbH
      • Braunschweig, Germany, D-38114
        • Medizinische Klinik Städtisches Klinikum Braunschweig gGmbH
      • Burg, Germany, 82335
        • Interne Klinik Dr. Argirov, Schön-Kliniken
      • Chemnitz, Germany, 09113
        • Klinik für Innere Medizin III Klinikum Chemnitz gGmbH
      • Dresden, Germany, 01307
        • Medizinische Klinik und Poliklinik, Uniklinikum Dresden
      • Düsseldorf, Germany, 40225
        • Universitaetsklinikum Dusseldorf Klinik fuer Haematologie
      • Essen, Germany, 45122
        • Direktor der Klinik f. Hämatologie, Universitätsklinikum Essen
      • Essen, Germany, 45122
        • Universitätsklinikum EssenInnere Klinik und Poliklinik
      • Frankfurt (Oder), Germany, 15236
        • Klinik für Innere Medizin, Klinikum Frankfurt (Oder) GmbH
      • Frankfurt am Main, Germany, 60590
        • Medizinische Klinik II (ZIM),Hämatologie / Onkologie Uniklinik Frankfurt
      • Freiburg, Germany, 79106
        • Abt. Innere Medizin I , Hämatologie / Onkologie, Universitätsklinikum Freiburg
      • Göttingen, Germany, 37075
        • Universitätsklinikum GöttingenHamatologie und Onkologie
      • Hamburg, Germany, 20246
        • Interdisziplinäre Klinik und Poliklinik für Stammzellentransplantation Universitätsklinik Hamburg - Eppendorf
      • Hamburg, Germany, 22763
        • II. Medizinische Abteilung, Asklepios Klinikum Altona
      • Hannover, Germany, 30625
        • Abt. Hämatologie, Hämatologie und Onkologie, Medizinische Hochschule Hannover
      • Heidelberg, Germany, 69120
        • Medizinische Klinik und Poliklinik V Universitaetsklinikum Heidelberg
      • Jena, Germany, 07740
        • Klinik für Innere Medizin II Hämatologie / Onkologie Universitätsklinikum Jena
      • Jena, Germany, 07743
        • EPS - Early Phase Solutions GmbH
      • Karlsruhe, Germany, 76135
        • Hämatologie / Onkologie / Infektionskrankheiten, Palliativmedizin Städtisches Klinikum Karlsruhe
      • Kiel, Germany, 24105
        • 2. Med. Klinik , Sektion f. Stammzell- + Immuntherapie Universitätsklinikum Schleswig-Holstein
      • Koblenz, Germany, 56068
        • Institut für Versorgungsforschung in der Onkologie Praxisklinik für Hämatologie und Onkologie
      • Köln, Germany, 50677
        • Ärzte f. Innere Medizin Gemeinschaftspraxis f. Hämatologie u. Onkologie
      • Köln, Germany, 50924
        • Klinik f. Innere Medizin, Klinikum der Universität zu Köln
      • Leipzig, Germany, 04103
        • Medizinische Klinik und Poliklinik II Abt. Hämatologie / Onkologie, Universitätsklinikum Leipzig AÖR
      • Mainz, Germany, 55101
        • III. Med. Klinik, Johannes Gutenberg Universität
      • Mannheim, Germany, 68305
        • Klinikum Mannheim der Universität Heidelberg
      • Mönchengladbach, Germany, 41239
        • Hämatologisch-Onkologisches Institut für medizinische Service Leistungen
      • München, Germany, 81377
        • Medizinische Klinik III Klinikum der Universität München-Großhadern
      • Münster, Germany, 48129
        • Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster
      • Münster, Germany, 48149
        • Facharzte fur Innere Medizin Hämatologie und Onkologie Gemeinschaftspraxis
      • Oldenburg, Germany, 26121
        • Onkologie Praxis Oldenburg
      • Oldenburg, Germany, 26133
        • Abt. Onkologie/ Hämatologie, Klinikum Oldenburg
      • Potsdam, Germany, 14467
        • Abteilung Hämatologie und Onkologie, Hämatologie und Onkologie, Medizinische Klinik, Klinikum Ernst v. Bergmann
      • Regensburg, Germany, 93053
        • Klinikum der Universität Regensburg
      • Rostock, Germany, 18057
        • Abteilung Hämatologie und Onkologie, Medizinische Fakultät der Universität Rostock
      • Saarbrucken, Germany, 66113
        • Caritasklinik St. Theresia
      • Saarbrucken, Germany, D-66113
        • ms² Medizinische Statistik Saarbrücken
      • Siegen, Germany, 57072
        • Med. Klinik III , St. Marienkrankenhaus Siegen
      • Stuttgart, Germany, D -70376
        • Zentrum für Innere Medizin II Robert- Bosch-Krankenhaus GmBH
      • Trier, Germany, 54290
        • Krankenanstalt Mutterhaus der Borromaerinnen
      • Tübingen, Germany, 72076
        • Abt. II Hämatologie, Onkologie und Immunologie Medizinische Klinik Abt.II
      • Ulm, Germany, 89081
        • Medizinische Universitätsklinik
      • Wuerselen, Germany, 52146
        • Praxis Dres. Maintz & GroschekHämatologie / Onkologie
      • Wuppertal, Germany, 42283
        • Med. Klinik 1, Helios Klinikum Wuppertal
      • Würzburg, Germany, 97080
        • Med. Klinik u. Poliklinik IIKlinikum der Universität Würzburg
      • Würzburg, Germany, D-97070
        • Hämatologisch-onkologische Praxis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • The development of a desquamating rash while taking thalidomide.
  • Neuropathy ≥ Grade 2.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: lenalidomide plus dexamethasone
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
Oral lenalidomide at a dose of 25 mg daily for 21 days every 28 days. Treatment as tolerated until disease progression.
Other Names:
  • Revlimid®
Drug: dexamethasone
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Kaplan Meier Estimate for Time to Disease Progression
Time Frame: up to 827 days

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participant's Best Overall Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Criteria
Time Frame: Up to 827 days

Best overall response was calculated as the best assessment from all cycles (including treatment discontinuation visit) and follow-up. The response rate was summarized as complete response (CR), partial response (PR), stable disease (SD), progression (PD), response not evaluable, and derived categories (PR+CR) and (PR+CR+SD).

CR is negative immunofixation on both serum and urine maintained for 6 weeks straight. PR is a 50% decrease in serum paraprotein maintained for 6 weeks straight. SD is serum paraprotein values within 25% of baseline.
Up to 827 days
Participants With Treatment-emergent Adverse Experiences (TEAEs)
Time Frame: up to 8 months

Counts of study participants who had treatment-emergent adverse events (TEAEs) defined as any reported AE that started on or after the first day of study drug dosing. A participant with multiple occurrences of an adverse event within a category is counted only once in that category.

National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) was used by investigators to assess TEAEs. Severity scale ranges from 0 (none) to 5 (death). Grade 3=severe AE; Grade 4=life threatening or disabling AE; Grade 5=death.
up to 8 months
Time to Partial Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Determination Criteria
Time Frame: up to 827 days
Time to partial response is the time from randomization to a 50% decrease in serum paraprotein maintained for six weeks straight. This was determined by free light chain concentrations which were taken every two weeks during the treatment phase of the trial.
up to 827 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celgene Corporation

Investigators

  • Principal Investigator: Axel Glasmacher, MD, University of Bonn

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

November 1, 2007

Study Completion (Actual)

August 1, 2009

Study Registration Dates

First Submitted

May 23, 2007

First Submitted That Met QC Criteria

May 24, 2007

First Posted (Estimate)

May 25, 2007

Study Record Updates

Last Update Posted (Estimate)

November 3, 2011

Last Update Submitted That Met QC Criteria

September 26, 2011

Last Verified

September 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CC-5013-MM-019
  • 2006-004532-73 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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