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

Relapsed or Refractory Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00478777
• Other study ID #: CC-5013-MM-019
• Secondary ID: 2006-004532-73
• Status: Completed
• Phase: Phase 3
• First received: May 23, 2007
• Last updated: September 26, 2011
• Start date: March 2007
• Est. completion date: August 2009

Study information

• Verified date: September 2011
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: August 2009
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed or Refractory Multiple Myeloma

Intervention

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

Locations

Country	Name	City	State
Germany	Medizinische Klinik und Poliklinik II der Charité Universitätsmedizin Berlin Campus Mitte	Berlin
Germany	Johanniter-Krankenhaus Bonn Friedrich-Wilhelm-Stift gGmbH	Bonn
Germany	Poliklinik I, Hämatologie/ Onkologie, Universitätsklinikum Bonn	Bonn
Germany	Medizinische Klinik Städtisches Klinikum Braunschweig gGmbH	Braunschweig
Germany	Interne Klinik Dr. Argirov, Schön-Kliniken	Burg
Germany	Klinik für Innere Medizin III Klinikum Chemnitz gGmbH	Chemnitz
Germany	Medizinische Klinik und Poliklinik, Uniklinikum Dresden	Dresden
Germany	Universitaetsklinikum Dusseldorf Klinik fuer Haematologie	Düsseldorf
Germany	Direktor der Klinik f. Hämatologie, Universitätsklinikum Essen	Essen
Germany	Universitätsklinikum EssenInnere Klinik und Poliklinik	Essen
Germany	Klinik für Innere Medizin, Klinikum Frankfurt (Oder) GmbH	Frankfurt (Oder)
Germany	Medizinische Klinik II (ZIM),Hämatologie / Onkologie Uniklinik Frankfurt	Frankfurt am Main
Germany	Abt. Innere Medizin I , Hämatologie / Onkologie, Universitätsklinikum Freiburg	Freiburg
Germany	Universitätsklinikum GöttingenHamatologie und Onkologie	Göttingen
Germany	II. Medizinische Abteilung, Asklepios Klinikum Altona	Hamburg
Germany	Interdisziplinäre Klinik und Poliklinik für Stammzellentransplantation Universitätsklinik Hamburg - Eppendorf	Hamburg
Germany	Abt. Hämatologie, Hämatologie und Onkologie, Medizinische Hochschule Hannover	Hannover
Germany	Medizinische Klinik und Poliklinik V Universitaetsklinikum Heidelberg	Heidelberg
Germany	EPS - Early Phase Solutions GmbH	Jena
Germany	Klinik für Innere Medizin II Hämatologie / Onkologie Universitätsklinikum Jena	Jena
Germany	Hämatologie / Onkologie / Infektionskrankheiten, Palliativmedizin Städtisches Klinikum Karlsruhe	Karlsruhe
Germany	2. Med. Klinik , Sektion f. Stammzell- + Immuntherapie Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Institut für Versorgungsforschung in der Onkologie Praxisklinik für Hämatologie und Onkologie	Koblenz
Germany	Ärzte f. Innere Medizin Gemeinschaftspraxis f. Hämatologie u. Onkologie	Köln
Germany	Klinik f. Innere Medizin, Klinikum der Universität zu Köln	Köln
Germany	Medizinische Klinik und Poliklinik II Abt. Hämatologie / Onkologie, Universitätsklinikum Leipzig AÖR	Leipzig
Germany	III. Med. Klinik, Johannes Gutenberg Universität	Mainz
Germany	Klinikum Mannheim der Universität Heidelberg	Mannheim
Germany	Hämatologisch-Onkologisches Institut für medizinische Service Leistungen	Mönchengladbach
Germany	Medizinische Klinik III Klinikum der Universität München-Großhadern	München
Germany	Fachärzte für Innere Medizin Hämatologie und Onkologie Gemeinschaftspraxis	Münster
Germany	Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster	Münster
Germany	Abt. Onkologie/ Hämatologie, Klinikum Oldenburg	Oldenburg
Germany	Onkologie Praxis Oldenburg	Oldenburg
Germany	Abteilung Hämatologie und Onkologie, Hämatologie und Onkologie, Medizinische Klinik, Klinikum Ernst v. Bergmann	Potsdam
Germany	Klinikum der Universität Regensburg	Regensburg
Germany	Abteilung Hämatologie und Onkologie, Medizinische Fakultät der Universität Rostock	Rostock
Germany	Caritasklinik St. Theresia	Saarbrucken
Germany	ms² Medizinische Statistik Saarbrücken	Saarbrucken
Germany	Med. Klinik III , St. Marienkrankenhaus Siegen	Siegen
Germany	Zentrum für Innere Medizin II Robert- Bosch-Krankenhaus GmBH	Stuttgart
Germany	Krankenanstalt Mutterhaus der Borromäerinnen	Trier
Germany	Abt. II Hämatologie, Onkologie und Immunologie Medizinische Klinik Abt.II	Tübingen
Germany	Medizinische Universitätsklinik	Ulm
Germany	Praxis Dres. Maintz & GroschekHämatologie / Onkologie	Wuerselen
Germany	Med. Klinik 1, Helios Klinikum Wuppertal	Wuppertal
Germany	Hämatologisch-onkologische Praxis	Würzburg
Germany	Med. Klinik u. Poliklinik IIKlinikum der Universität Würzburg	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
Celgene Corporation

Country where clinical trial is conducted

Germany, 

References & 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,

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Participant's Best Overall Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Criteria	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	No
Secondary	Participants With Treatment-emergent Adverse Experiences (TEAEs)	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	Yes
Secondary	Time to Partial Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Determination Criteria	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	No