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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00478777
First received: May 23, 2007
Last updated: September 26, 2011
Last verified: September 2011
  Purpose

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.


Condition Intervention Phase
Relapsed or Refractory Multiple Myeloma
Drug: Lenalidomide
Drug: dexamethasone
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Single-Arm, Open-Label Expanded Access Program for Lenalidomide Plus Dexamethasone in Previously Treated Subjects With Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Kaplan Meier Estimate for Time to Disease Progression [ Time Frame: up to 827 days ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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.


  • Participants With Treatment-emergent Adverse Experiences (TEAEs) [ Time Frame: up to 8 months ] [ Designated as safety issue: Yes ]

    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.


  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 150
Study Start Date: March 2007
Study Completion Date: August 2009
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Lenalidomide
  • 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.
Other Name: dexamethasone

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00478777

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

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

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00478777     History of Changes
Other Study ID Numbers: CC-5013-MM-019, 2006-004532-73
Study First Received: May 23, 2007
Results First Received: September 26, 2011
Last Updated: September 26, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Celgene Corporation:
CC-5013
Revlimid
Lenalidomide
Celgene
Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on July 20, 2014