A Phase II, Open-Label Trial Using VELCADE for Re-Treatment of Multiple Myeloma Subjects Following an Initial Response to VELCADE

• Conditions: multiple myeloma; Classification code 10028228

• Registration Number: EUCTR2005-005819-26-GR
• Lead Sponsor: Janssen-Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-09-01
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 125

Inclusion Criteria

1. Male or female subject, aged >= 18 years.
2. 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performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
3. Subject was previously diagnosed with multiple myeloma based on standard criteria and has measurable disease. 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 0.5g/dL immunoglobulin A (IgA)) or urine light-chain excretion of >= 200 mg/24 hours.
4. Subject previously tolerated 1.0 or 1.3 mg/m2/dose of VELCADE alone or in combination with other agents and had CR or PR upon completion of VELCADE therapy.
5. It has been >= 6 months since the subject's last VELCADE dose and the subject has Progressive Disease (PD) if prior response to VELCADE was PR or subject has relapsed from CR. PD or relapse are defined as one or more of the following criteria:
Criteria for PD for subjects that had PR to previous VELCADE course:
· >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.
6. Subject has a Karnofsky performance status >=60% (see Attachment 1: Karnofsky Performance Status Scale).
7. Subject has a life-expectancy >3 months.
8. Subject has the following laboratory values within 14 days before enrolment (Day 1, Cycle 1, before drug administration):
· Platelet count >=50 x 10 exp.9/L without transfusion support within the 7 days before the test;
· Hemoglobin >=7.5 g/dL without transfusion support within 7 days before the test;
· Absolute neutrophil count (ANC) >=0.75 x 10 exp.9/L without the use of growth factors within 14 days before the test;;
· Corrected serum calcium <14 mg/dL (3.5 mmol/L);
· Aspartate aminotransferase (AST) <=2.5 x the upper limit of normal (ULN);
· Alanine aminotransferase (ALT) <=2.5 x the ULN;
· Total bilirubin <=1.5 x the ULN; and
· Calculated or measured creatinine clearance >=20 mL/minute (see Attachment 2: Creatinine Clearance Calculation for formula to calculate clearance from serum creatinine).
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 completion of the last treatment cycle.
10. If male, the subject agrees to use an acceptable barrier method for contrac

Exclusion Criteria

1. Subjects with a history of PD, minimal response, or stable disease (SD) on last exposure to VELCADE.
2. Subject has received chemotherapy, radiotherapy, antibody, immunotherapy, or experimental therapy to treat multiple myeloma since their last dose of VELCADE. Note: Subjects can have received localized palliative radiotherapy for complications due to osteolytic bone lesions. Subjects can have received steroids (Dexamethasone or equivalent) or thalidomide or Interferon as maintenance therapy since their last dose of VELCADE 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 4 weeks prior to enrollment. Subjects can have received high dose therapy/stem cell transplantation after VELCADE containing induction regimen, only if PR or CR was observed during VELCADE containing induction therapy.
3. Subjects who achieved a CR or PR but relapsed while on therapy.
4. Subject has oligosecretory or non-secretory multiple myeloma.
5. Subject had major surgery within 4 weeks before enrolment. (Kyphoplasty is not considered major surgery.)
6. Subject has a history of allergic reaction to VELCADE or attributable to compounds containing boron or mannitol.
7. Subject has peripheral neuropathy or neuropathic pain of >= Grade 2, as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0.
8. Subject has cardiac amyloidosis.
9. Subject has an uncontrolled or severe cardiovascular disease, including myocardial infarction within 6 months of enrolment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
10. 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.
11. Subject had another malignancy within the past 5 years. Exceptions for the following if treated and not active: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or International Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix.
12. 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).
13. 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 should be tested in accordance with local policies).
14. Subject has an active systemic infection requiring treatment.
15. Female subject is pregnant or breast feeding. Confirmation that the subject is not pregnant must be established by a negative B-HCG pregnancy test result obtained during the Screening period. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
16. Subjects that have been previously enrolled in this trial
17. Subjects that have taken any experimental therapy or used any experimental device within 30 days prior to the enrolment.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine best response to VELCADE re-treatment in multiple myeloma subjects who have previously responded to a VELCADE based therapy.<br>;Secondary Objective: · Determine the incidence of SAEs, Grade 3 and 4 AEs, and all grades of neuropathy from each subject at baseline and every 6 weeks during treatment.<br>· Determine best confirmed M-protein response to VELCADE re-treatment in multiple myeloma subjects who have previously responded to VELCADE.<br>· Determine the DOR and TTP.;Primary end point(s): To determine best response to VELCADE re-treatment in multiple myeloma subjects who have previously responded to a VELCADE based therapy.