Refractory or relapsed multiple myeloma after 1 to 3 previous lines of therapy, including high-dose therapy MedDRA version: 14.1 Level: PT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: VELCADE 3,5 mg Pulver zur Herstellung einer Injektionslösung
Product Code: PS-341, 26866138-AAA-PB-001
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Bortezomi
Sponsors
ORTHO BIOTECH, Division of JANSSEN-CILAG GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female =18 years of age 2. Informed consent 3. Diagnosis of multiple myeloma and measurable disease (serum M-protein =1g/dL (10g/L, urine light-chain excretion =200mg/24h, involved FLC level =10mg/dL provided sFLC ratio is abnormal) 4. Relapse or refraction of multiple myeloma following 1-3 previous lines of therapy and requires treatment. The subject has undergone or is not eligible for bone marrow transplantation. 5. Karnofsky status =60% 6. Life expectancy estimated at screening of at least 6 months 7. Willingness or ability to comply in the investigator's opinion 8. Women must be postmenopausal or surgically sterilized; women of childbearing potential must use a safe method of contraception before entry and throughout the study and have a negative pregnancy test at screening. Accepted is also a male partner vasectomized 9. Male patients must use a reliable method of contraception from screening up to 6 months after trial completion. 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 21 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 89
Exclusion criteria
Exclusion criteria: 1. More than three previous lines of therapy for multiple myeloma 2. Known allergy or hypersensitivity to bortezomib, dexamethasone and/or cyclo- phosphamide or to any of the constituent compounds containing boron, mannitol, or lactose 3. Progressive disease or stable disease under bortezomib in a previous line of therapy 4. Oligosecretory or non-secretory multiple myeloma 5. Reception of nitrosoureas or any other chemotherapy within 6 weeks before enrolment 6. Reception of corticosteroids (>10 mg/day prednisone or equivalent) within 3 weeks before enrolment 7. Immunotherapy or antibody therapy for multiple myeloma within 8 weeks before enrolment (Ig substitution therapy is not excluded) 8. Plasmapheresis within 2 weeks before enrolment 9. Major surgery within 4 weeks before enrolment (kyphoplasty is not considered major surgery) 10. Peripheral neuropathy or neuropathic pain of grade 2 or greater intensity, as defined by NCI CTCAE, version 3.0 11. Uncontrolled or severe cardiovascular disease, including myocardial infarction within 6 months before enrolment or NYHA Class III or IV heart failure, uncon- trolled angina, acute diffuse infiltrative pulmonary and pericardial disease, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, active conduction system abnormalities or cardiac amyloidosis 12. Clinically relevant or poorly controlled vascular, pulmonary, gastrointestinal, endocrine, neurological, psychiatric or metabolic diseases, which could potentially interfere with the completion of treatment according to protocol subject has urinary tract obstruction or cystitis before start of therepy Subject has liver or renal insufficiency indicated by one or more of the following pre-treatment laboratory values within 14 days before and at baseline: · platelet count 2,5 × the upper limit of normal (ULN) · alanine transaminase (ALT) > 2,5 × ULN · total bilirubin > 1,5 × ULN 13. Malignancy other than multiple myeloma within 5 years before enrolment: Exceptions for the following if treated and not active: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or FIGO Stage 1 of the cervix 14. HIV positive status. When assessed by the investigator to be at risk for HIV testing in accordance with local policies 15. Positive status of hepatitis B surface antigen or known active hepatitis C. When assessed by the investigator to be at risk for hepatitis B or C testing in accordance with local regulations 16. Systemic infection requiring treatment 17. Use of disallowed concomitant medication 18. Participation in other clinical studies conducted in parallel and participation in a clinical study, i.e. subject has received an experimental drug or used an ex- perimental medical device, within 30 days prior to enrolment in this study. This does n
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determination of efficacy as time to progression of the standard therapy of bortezomib and low dose dexamethasone in combination with or without continuous low dose oral cyclophosphamide in patients with primary refractory or relapsed myeloma (1st - 3rd relapse).;Secondary Objective: Determination of · overall survival · progression free survival · best response rate according to IMWG 2006 criteria · safety · change in Karnofsky Performance Status Score and the quality of life by EQ-5D questionnaire · the health economic impact by rate of skeletal related events (SRE) and necessity for dialysis due to renal insufficiency ;Primary end point(s): Time to progression (TTP), defined as time from randomisation to first observation of disease progression, censoring for death or drop out without progression. Patients who died or dropped out due to any other reason without progression will be censored with the day of death or drop-out, respectively. Patients who are alive at the end of the study and have no progression will be censored with the last available date. For review of the primary endpoint a central expert panel will be implemented. ;Timepoint(s) of evaluation of this end point: defined as time from randomisation to first observation of disease progression, censoring for death or drop out without progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival, Progression free survival, Best response rate according to IMWG criteria, Safety parameters, Change in Karnofsky Index from baseline to EoT, Quality of life assessed by EQ-5D, Rate of sceletal related events, Rate of necessity for dialysis due to renal insufficiency;Timepoint(s) of evaluation of this end point: study end, End of Treatmenmt | — |
Countries
Germany
Contacts
Public ContactProjektleiter Dr. Carsten Gerdemann
ORTHO BIOTECH Division of Janssen-Cilag GmbH
Outcome results
None listed