A Phase 2, Multicentre, Randomised, Open-Label, Parallel Group Study to Evaluate the Safety and Efficacy of VELCADE® in combination with Dexamethasone or VELCADE® in combination with Dexamethasone and Cyclophosphamide or VELCADE® in combination with Dexamethasone and Lenalidomide in Subjects with Multiple Myeloma who are Refractory to or Have Relapsed / progressed after Primary Therapy for Multiple Myeloma and have achieved stable disease after 4 cycles of VELCADE®/Dexamethasone therapy

Phase 1

• Conditions: multiple myeloma; MedDRA version: 9.1 Level: LLT Classification code 10028228 Term: Multiple myeloma

• Registration Number: EUCTR2007-001462-33-GB
• Lead Sponsor: Janssen-Cilag International N.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-02-01
• Study Completion: 2011-08-02
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

1. Male or female subject, aged =18 years.
2. The subject has relapsed/progressed or is refractory for multiple myeloma following 1 previous line of therapy.
Progressive Disease (PD) or relapse are defined as one or more of the following criteria:
Criteria for PD:
•=25% increase from lowest response level in serum M-component and/ or (the absolute increase must be > 0.5 g/dl)
•=25% increase from lowest response level in urine M-component and/or (the absolute increase must be > 200 mg/24 h);
•Bone marrow plasma cell percentage: the absolute % must be = 10%;
•Definite development of new bone lesion or soft-tissue plasmacytomas or definite increase in size of existing bone lesion or soft-tissue plasmacytomas;
•Development of hypercalcemia (corrected serum calcium >11.5 mg/dl or 2.65 mmol/l) that can be attributed solely to the plasma cell proliferative disorder.
Criteria for relapse from CR:
•Reappearance of serum or urine M-protein by immunofixation or electrophoresis
•Development of =5% plasma cells in bone marrow
•Appearance of any other sign of progression (i.e., new lytic bone lesion or new plasmacytomas or hypercalcemia).
All relapse categories require two consecutive assessments made at anytime before classification as relapse or disease progression.
3. Measurable secretory multiple myeloma: measurable disease for secretory multiple myeloma is defined by at least one of the following measurements: serum monoclonal protein greater than or equal to 1 g/dl (= 10 gm/l) [10g/l], urine M-protein of =200 mg/24 hours.
4. Subject has a Karnofsky performance status of =60.
5. Subject has a life expectancy estimated at screening of at least 6 months.
6. 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 10^9/L without transfusion support within the 7 days before the test
•Hemoglobin = 7.5 g/dL without transfusion support within the 7 days before the test
•Absolute neutrophil count (ANC) =0.75 x 10^9/L without the use of colony stimulating factors within 14 days before the test
•Corrected serum calcium < 14 mg/dL (3.5 mmol/L).
•Aspartate transaminase (AST): =2.5 x the upper limit of normal (ULN).
•Alanine transaminase (ALT): =2.5 x ULN.
•Total bilirubin: =1.5 x ULN.
7. The subject is, in the investigator’s opinion, willing and able to comply with the protocol requirements.
8. 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.
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 six months following treatm

Exclusion Criteria

1.Subject received more than one previous line of therapy for multiple myeloma.
2.Subject has known allergy or hypersensitivity to bortezomib, Dexamethasone and/or Cyclophosphamide and/or Lenalidomide or any of the constituents compounds such as boron, mannitol, or lactose.
3.Subject has oligosecretory or non-secretory multiple myeloma.
4.Subject received nitrosoureas or any other chemotherapy (including thalidomide), clarithromycin, interferon within 6 weeks before enrolment. Note: subjects can have received thalidomide or interferon as mantainance therapy, according to local standard of care.
5.Subject received corticosteroids (> 10 mg/day prednisone or equivalent) within 3 weeks before enrolment. Note: subjects can have received steroids (dexamethasone or equivalent) as maintenance therapy according to local standard of care. In addition, subjects can have received a cumulative dose of up to 160 mg of dexamethasone or equivalent as emergency therapy within 3 weeks prior to study entry.
6.Subject received immunotherapy or antibody therapy within 8 weeks before enrolment.
7.Subject received plasmapheresis within 2 weeks before enrolment.
8.Subject had major surgery within 4 weeks before enrolment (kyphoplasty was not considered major surgery).
9.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.
10.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.
11.Subject has poorly controlled hypertension, diabetes mellitus, or other serious medical condition (such as severe hepatic impairment, pericardial disease, acute diffuse infiltrative pulmonary disease, systemic infections etc) or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
12.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.
13.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.
14.Subject is known to be hepatitis B surface antigen-positive or has 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.)
15.Subject has an active systemic infection requiring treatment.
16.Subject uses disallowed medication
17.Subject has received an experimental drug or used an experimental medical device within 4 weeks before enrolment.
18.If female, the subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative 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