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

• Conditions: Multiple myeloma; MedDRA version: 8.1Level: LLTClassification code 10028228Term: Multiple myeloma

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-09-27
• Last Update Posted: 7 January 2013

Recruitment & Eligibility

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

Inclusion Criteria

1. Male or female subject, aged 18 or more 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that consent may be withdrawn by the subject at any time without prejudice to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 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 0,5 g/dl immunoglobulin A (IgA) or urine light-chain
excretion of 200 mg or more in 24 hours.
4. Subject previously tolerated 1,0 or 1,3 mg/m²/dose of VELCADE alone or in com-
binationwith other agents and CR or PR upon completion of VELCADE therapy.
5. It has been 6 months or more 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 of 60% or more.
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 of 7,5 g/dl or more without transfusion support within 7 days
before the test;
- Absolute neutrophil count (ANC) 0,75 x 10 exp.9/l ore more 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) or less;
- Alanine aminotransferase (ALT) 2,5 x the ULN or less;
- Total bilirubin 1,5 x the ULN or less;
- Calculated or measured creatinine clearance 20 ml/minute or more
9. If female, the subject is either postmenopausal or surgically sterilised or willing
to use an acceptable method of birth control from screening through at least 30
days after completion of the last treatment cycle.
10. If male, the subject agrees to use an accept

Exclusion Criteria

1. Subject 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 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. 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 CR or PR but relapse 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 history of allergic reaction to VELCADE or compounds containing
boron or mannitol.
7. Subject has peripheral neuropathy or neuropathic pain of Grade 2 or higher, as
defined by NCI CTCAE Version 3.0.
8. Subject has cardiac amyloidosis.
9. Subject has an uncontrolled or severe cardiovascular disease, including myo-
cardial infarction within 6 months of enrolment or has 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 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 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. (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 gregnant 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 an experimental therapy or used any experimental
device within 30 days prior to enrolment.

Study & Design

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