Multiple Myeloma MedDRA version: 18.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Revlimid
Product Name: lenalidomide
Product Code: L04AX04
Pharmaceutical Form: Capsule, hard
Trade Name: Endoxan
Product Name: cyclophosphamide
Product Code: PL 00116/0392
Pharmaceutical
Sponsors
VU University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Multiple myeloma/Salmon & Durie stage II/III A or B • Previous lenaliomide- refractory disease (refractory to prior treatment indicates progressive disease on last prior therapy, best response of stable disease (not CR, VGPR, PR or PD) to last prior therapy, or progressive disease within 3 months (International Uniform Response Criteria for Multiple Myeloma)) is required in both the phase 1 and 2 part of the study1 • ? 1 previous line of treatment • Age ? 18 years • WHO performance 0, 1, 2, or 3 • Measurable disease i.e. serum M-protein (>10 g/l), or urinary light-chain excretion (>200 mg/24 h), or proven plasmacytoma by biopsy • Life expectancy at least 3 months • Written informed consent • Patient commits to pregnancy prevention program (for detailed information see section 10.1) •Negative pregnancy tests before inclusion if female of child baring potential; Sexually active women of child bearing potential must agree to use 2 reliable forms of adequate contraception while on study drug (and 4 weeks before and after study drug) (for detailed information see section 10.1) Men must agree not to father a child and to use a condom if his partner is of childbearing potential 1) A therapy-free interval or other lines of therapy between prior lenalidomide therapy and REP is allowed Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: • Non-secretory myeloma • Known hypersensitivity to lenalidomide • Inadequate marrow reserve as defined by a platelet count <100 x 109/L or an absolute neutrophil count <1.5 x 109/L • Systemic AL amyloidosis • Uncontrolled or severe cardiovascular disease (NYHA class III or IV heart failure; myocardial infarction within the last 6 months of study entry); unstable angina; unstable cardiac arrythmias; clinically significant pericardial disease) • Significant hepatic dysfunction (total bilirubin ? 3 times normal value or transaminases ? 3 times normal value), unless related to myeloma • Creatinine clearance <30 mL/min • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, etc.) • Patients known to be HIV-positive • History of active malignancy during the past 5 years, except basal carcinoma of the skin or stage 0 cervical carcinoma • Unable or unwillingness to comply with the pregnancy prevention program (for detailed information see section 10.1) • Not able and/or willing to use adequate contraception • Pregnant or lactating females
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 Primary objective - To determine the maximum tolerated dose (MTD) and recommended phase 2 dose level (RDL) of lenalidomide administered during 21 days of a 4 week cycle, combined with continuous cyclophosphamide and prednisone. Phase 2 pimary objective - To investigate the efficacy of lenalidomide administered during 21 days of a 4 week cycle, combined with continuous cyclophosphamide and prednisone at the RDL, as determined by the (s)CR+VGPR+PR rate. ;Secondary Objective: Phase 1 Secondary objective - To evaluate toxicity. Phase 2 Secondary objectives - To evaluate toxicity. - To evaluate progression-free survival - To evaluate overall survival - To evaluate prognostic factors for response and survival - To evaluate the immunomodulatory effects of lenalidomide by using flow cytometric and cytokine analysis ;Primary end point(s): Phase 1 Primary endpoint - Dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase 2 dose (RDL) of lenalidomide, cyclophosphamide, combined with prednisone (REP). Secondary endpoints - Toxicity, especially myelosuppression, polyneuropathy and thrombosis Phase 2 Primary endpoint - Overall response rate. In this analysis we will consider the best response obtained during treatment Secondary endpoints - Toxicity, especially myelosuppression, polyneuropathy and thrombosis - Progression free survival (PFS; i.e. time from registration to progression or death from any cause, whichever comes first - Overall survival measured from registration. Patients still alive or lost to follow up are censored at the date they were last known to be alive - Prognostic factors for response and survival - Immunomodulatory effects of lenalidomide by evaluation of T cell subsets and cytokine analysis | — |
Countries
Netherlands
Contacts
Public Contactexecutive coordinator REPEAT-study
University Medical Center Utrecht
Outcome results
None listed