Clinical trial NCT00478777: A Multicenter, Single-Arm, Open-Label Expanded Access Program for Lenalidomide Plus Dexamethasone in Previously Treated Subjects With Multiple Myeloma
Official title: A Multicenter, Single-Arm, Open-Label Expanded Access Program for Lenalidomide Plus Dexamethasone in Previously Treated Subjects With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: CC-5013
Revlimid
Lenalidomide
Celgene
Multiple Myeloma
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2007-05-25
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Kaplan Meier Estimate for Time to Disease Progression
timeFrame: up to 827 days
Secondary outcomes:
measure: Participant's Best Overall Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Criteria
timeFrame: Up to 827 days
measure: Participants With Treatment-emergent Adverse Experiences (TEAEs)
timeFrame: up to 8 months
measure: Time to Partial Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Determination Criteria
timeFrame: up to 827 days
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Medizinische Klinik und Poliklinik II der Charité Universitätsmedizin Berlin Campus Mitte
city: Bonn
country: Germany
facility: Poliklinik I, Hämatologie/ Onkologie, Universitätsklinikum Bonn
city: Bonn
country: Germany
facility: Johanniter-Krankenhaus Bonn Friedrich-Wilhelm-Stift gGmbH
city: Braunschweig
country: Germany
facility: Medizinische Klinik Städtisches Klinikum Braunschweig gGmbH
city: Burg
country: Germany
facility: Interne Klinik Dr. Argirov, Schön-Kliniken
city: Chemnitz
country: Germany
facility: Klinik für Innere Medizin III Klinikum Chemnitz gGmbH
city: Dresden
country: Germany
facility: Medizinische Klinik und Poliklinik, Uniklinikum Dresden
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Dusseldorf Klinik fuer Haematologie
city: Essen
country: Germany
facility: Direktor der Klinik f. Hämatologie, Universitätsklinikum Essen
city: Essen
country: Germany
facility: Universitätsklinikum EssenInnere Klinik und Poliklinik
city: Frankfurt (Oder)
country: Germany
facility: Klinik für Innere Medizin, Klinikum Frankfurt (Oder) GmbH
city: Frankfurt am Main
country: Germany
facility: Medizinische Klinik II (ZIM),Hämatologie / Onkologie Uniklinik Frankfurt
city: Freiburg
country: Germany
facility: Abt. Innere Medizin I , Hämatologie / Onkologie, Universitätsklinikum Freiburg
city: Göttingen
country: Germany
facility: Universitätsklinikum GöttingenHamatologie und Onkologie
city: Hamburg
country: Germany
facility: Interdisziplinäre Klinik und Poliklinik für Stammzellentransplantation Universitätsklinik Hamburg - Eppendorf
city: Hamburg
country: Germany
facility: II. Medizinische Abteilung, Asklepios Klinikum Altona
city: Hannover
country: Germany
facility: Abt. Hämatologie, Hämatologie und Onkologie, Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Medizinische Klinik und Poliklinik V Universitaetsklinikum Heidelberg
city: Jena
country: Germany
facility: Klinik für Innere Medizin II Hämatologie / Onkologie Universitätsklinikum Jena
city: Jena
country: Germany
facility: EPS - Early Phase Solutions GmbH
city: Karlsruhe
country: Germany
facility: Hämatologie / Onkologie / Infektionskrankheiten, Palliativmedizin Städtisches Klinikum Karlsruhe
city: Kiel
country: Germany
facility: 2. Med. Klinik , Sektion f. Stammzell- + Immuntherapie Universitätsklinikum Schleswig-Holstein
city: Koblenz
country: Germany
facility: Institut für Versorgungsforschung in der Onkologie Praxisklinik für Hämatologie und Onkologie
city: Köln
country: Germany
facility: Ärzte f. Innere Medizin Gemeinschaftspraxis f. Hämatologie u. Onkologie
city: Köln
country: Germany
facility: Klinik f. Innere Medizin, Klinikum der Universität zu Köln
city: Leipzig
country: Germany
facility: Medizinische Klinik und Poliklinik II Abt. Hämatologie / Onkologie, Universitätsklinikum Leipzig AÖR
city: Mainz
country: Germany
facility: III. Med. Klinik, Johannes Gutenberg Universität
city: Mannheim
country: Germany
facility: Klinikum Mannheim der Universität Heidelberg
city: Mönchengladbach
country: Germany
facility: Hämatologisch-Onkologisches Institut für medizinische Service Leistungen
city: München
country: Germany
facility: Medizinische Klinik III Klinikum der Universität München-Großhadern
city: Münster
country: Germany
facility: Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster
city: Münster
country: Germany
facility: Fachärzte für Innere Medizin Hämatologie und Onkologie Gemeinschaftspraxis
city: Oldenburg
country: Germany
facility: Onkologie Praxis Oldenburg
city: Oldenburg
country: Germany
facility: Abt. Onkologie/ Hämatologie, Klinikum Oldenburg
city: Potsdam
country: Germany
facility: Abteilung Hämatologie und Onkologie, Hämatologie und Onkologie, Medizinische Klinik, Klinikum Ernst v. Bergmann
city: Regensburg
country: Germany
facility: Klinikum der Universität Regensburg
city: Rostock
country: Germany
facility: Abteilung Hämatologie und Onkologie, Medizinische Fakultät der Universität Rostock
city: Saarbrucken
country: Germany
facility: Caritasklinik St. Theresia
city: Saarbrucken
country: Germany
facility: ms² Medizinische Statistik Saarbrücken
city: Siegen
country: Germany
facility: Med. Klinik III , St. Marienkrankenhaus Siegen
city: Stuttgart
country: Germany
facility: Zentrum für Innere Medizin II Robert- Bosch-Krankenhaus GmBH
city: Trier
country: Germany
facility: Krankenanstalt Mutterhaus der Borromäerinnen
city: Tübingen
country: Germany
facility: Abt. II Hämatologie, Onkologie und Immunologie Medizinische Klinik Abt.II
city: Ulm
country: Germany
facility: Medizinische Universitätsklinik
city: Wuerselen
country: Germany
facility: Praxis Dres. Maintz & GroschekHämatologie / Onkologie
city: Wuppertal
country: Germany
facility: Med. Klinik 1, Helios Klinikum Wuppertal
city: Würzburg
country: Germany
facility: Med. Klinik u. Poliklinik IIKlinikum der Universität Würzburg
city: Würzburg
country: Germany
facility: Hämatologisch-onkologische Praxis
Study officials:
affiliation: University of Bonn
name: Axel Glasmacher, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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