A Phase II, Multicentre, Randomised, Open-Label, Parallel Group Study to Evaluate the Safety and Efficacy of Velcade® added to Thalidomide-Dexamethasone Standard Treatment in Subjects with Multiple Myeloma who are Refractory to or Have Relapsed after Primary Therapy for Multiple Myeloma - Velcade added to Thal-Dex in 2nd line multiple myeloma

• Conditions: multiple myeloma; Classification code 10028228

• Registration Number: EUCTR2005-004624-38-FI
• Lead Sponsor: Janssen-Cilag EMEA Medical Affairs

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-07-03
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 212

Inclusion Criteria

1. Male or female subject, aged >= 18 years.
2. The subject has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her medical care.
3. Measurable secretory multiple myeloma: measurable disease for secretory multiple myeloma is defined as any quantifiable serum monoclonal protein value (generally, but not exclusively, greater than 1 g/dL of immunoglobulin G (IgG) M-protein and greater than 0.5 g/dL immunoglobulin A (IgA) or urine light-chain excretion of >=200mg/24 hours.
4. The subject has relapsed or is refractory for multiple myeloma following 1 previous line of therapy and, is scheduled by the investigator to be treated with Thal-Dex standard therapy. PD or relapse are defined as one or more of the following criteria:
Criteria for PD:
Criteria for PD for subjects not in CR
· >25% increase in either serum or urine M-protein;
· >25% increase in plasma cells on bone marrow;
· Definite increase in size of bone lesion or plasmacytoma;
· Development of new bone lesion or plasmacytoma; or
· Development of hypercalcemia (corrected serum calcium >11.5 mg/dl or 2.8 mmol/l) not attributable to other causes.
Criteria for relapse from CR
· reappearance of serum or urinary paraprotein on immunofixation or routine electrophoresis, confirmed by at least one further investigation and excluding oligoclonal immune reconstitution
· >5% plasma cells in bone marrow aspirate or on trephine bone biopsy
· Development of new lytic bone lesions or soft tissue plasmacytomas or definite increase in the size of residual bone lesions
· Development of hypercalcemia (corrected serum calcium >11,5 mg/dl or 2.8 mmol/l) not attributable to any other cause.
5. Subject has a Karnofsky performance status of >= 60 (see Attachment 1).
6. The subject has a life expectancy estimated at screening of at least 6 months
7. The subject meets the following pretreatment laboratory criteria at and within 14 days before baseline (Day 1 of Cycle 1, before study drug administration):
- platelet count >= 50x 10 exp9/L;
- haemoglobin >7.5 g/dl without transfusion support within 7 days before the test;
- creatinine clearance >= 20 mL/min (calculated or measured) (see Attachment 2).
- absolute neutrophil count (ANC) >= 0.75 ´ 109/L without the use of colony stimulating factors.
- corrected serum calcium < 14 mg/dL (3.5 mmol/L).
- aspartate transaminase (AST): <= 2.5 x upper limit of normal (ULN).
- alanine transaminase (ALT): <= 2.5 x ULN.
- total bilirubin: <= 1.5 x ULN.
Note: If the screening laboratory tests were performed within 2 weeks before baseline, the screening laboratory tests do not need to be repeated at baseline if in the investigator's opinion it is very likely that the results will be unchanged.
- If the screening laboratory tests were performed more than 2 weeks before baseline, the screening laboratory tests have to be repeated at baseline.
8. The subject is, in the investigator's opinion, willing and able to comply with the protocol requirements.
9. If female, the subject is either postmenopausal or surgically sterilised or willing to use an acceptable method of birth control (i.e., total abstinence -periodic abstinence can not be allowed-, a hormonal contraceptive, intrauterine device, diaphragm with spermicide, or condom with spermicide) from screening through at least 30 days after compl

Exclusion Criteria

1. Subject received more than one previous line of therapy for multiple myeloma.
2. Use of Velcade® or thalidomide in the previous line of therapy.
3. The subject received Velcade® in a previous trial.
4. Subject has known allergy or hypersensitivity to bortezomib, boron or mannitol.
5. Subject has oligosecretory or non-secretory multiple myeloma.
6. Subject received nitrosoureas or any other chemotherapy (including thalidomide), clarithromycin, interferon within 6 weeks of enrollment.
7. Subject received corticosteroids (> 10 mg/day prednisone or equivalent) within 3 weeks before enrolment.
8. Subject received immunotherapy or antibody therapy within 8 weeks before enrolment.
9. Subject received plasmapheresis within 4 weeks before enrolment.
10. Subject had major surgery within 4 weeks before enrolment (kyphoplasty is not considered major surgery).
11. Subject has peripheral neuropathy or neuropathic pain of grade 2 or greater intensity, as defined by the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI CTCAE), version 3.0 (see attachment 6 for link).
12. Subject had a myocardial infarction within 6 months of enrolment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
13. Subject has poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
14. Subject was treated for a cancer other than multiple myeloma within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ.
15. Subject is known to be human immunodeficiency virus (HIV)-positive. Subjects assessed by the investigator to be at risk for HIV infection should be tested in accordance with local policies.
16. Subject was known to be hepatitis B surface antigen-positive or had known active hepatitis C infection. (Subjects assessed by the investigator to be at risk for hepatitis B or C infection are to be tested in accordance with local regulations.)
17. Subject had an active systemic infection requiring treatment.
18. Subject has a history of thrombovascular event within the last 6 months.
19. Subject uses disallowed medication (see section 8).
20. Subject has received an experimental drug or used an experimental medical device within 4 weeks before enrolment.
21. If female, the subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum pregnancy test at screening. Pregnancy testing is not required for postmenopausal or surgically sterilised women.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified