A Randomized, Open-Label, Phase 2 Study of CNTO 328 (Anti-IL-6 Monoclonal Antibody) and Velcade-Melphalan-Prednisone Compared with Velcade-Melphalan-Prednisone for the Treatment of Previously Untreated Multiple Myeloma
The goal of this clinical research study is to learn if the combination of Siltuximab (CNTO 328) and VMP (a combination of the drugs Velcade [bortezomib], melphalan, and prednisone) can more effectively control MM than VMP alone. The safety of this combination will also be studied.
Disease Group: Myeloma
Treatment Agent: Bortezomib
Treatment Location: Both at MD Anderson & outside MD Anderson at one or more Collaborating Sites or Institutions
Estimatated Length of Stay in Houston: No hospitalization required.
Sponsor: Janssen Research & Development
Return Visit: Cycles 1-4 Velcade - Days 1,4,8,11,22,25,29,32 MP-Days 1-4 CNTO 328 - Days 1, 22 Cycles 5-9 Velcade - Days 1, 8, 22, 29 MP - Days 1-4 CNTO 328 - Days 1, 22
Home Care: No home care.
Primary Objective In subjects with previously untreated multiple myeloma, the primary objectives of the study are: Part 1 To assess the safety of CNTO 328 at a dose of 11 mg/kg every 3 weeks when administered in combination with Velcade, melphalan, and prednisone (VMP). Part 2 To demonstrate improved efficacy, as assessed by complete remission (CR) rate using the European Group for Blood and Marrow Transplantation (EBMT) criteria, of CNTO 328 in combination with VMP. Secondary Objectives In subjects with previously untreated multiple myeloma, the secondary objectives of the study are: Part 1 To explore the efficacy, pharmacokinetics, and pharmacodynamics of CNTO 328 in combination with VMP. Part 2 To assess additional measures of clinical benefit, safety, pharmacokinetics, and biomarkers of CNTO 328 in combination with VMP.
IRB Review and Approval Date: 07/09/2010
Recruitment Status: Not Accepting
Projected Accrual: 116
1) Male or female >/= 18 years of age at screening
2) Subjects (or their legally acceptable representatives) must have signed informed consent indicating that they understand the purpose of and procedures required for the study, and are willing to participate in the study. Informed consent must be obtained before performing any study-specific procedures.
3) Eastern Cooperative Oncology Group (ECOG) Performance Status score of </= 2
4) Confirmed diagnosis of multiple myeloma (International Myeloma Working Group [IMWG] criteria requiring treatment
5) Subject is not a candidate for high-dose chemotherapy with stem cell transplantation due to: Age >/= 65 years, or In subjects < 65 years: presence of important comorbid condition(s) likely to have a negative impact on the tolerability of high-dose chemotherapy with stem cell transplantation.
6) Measurable secretory disease, defined as either serum monoclonal paraprotein (M-protein) >/= 1 g/dL or urine monoclonal (light chain) protein > 200 mg/24 hours
7) Have pretreatment clinical laboratory values meeting the following criteria within 14 days before treatment: Hemoglobin >/= 8 g/dL (>/= 4.96 mmol/L; prior red blood cell (RBC) transfusion or recombinant human erythropoietin use is permitted); Absolute neutrophil count (ANC) >/= 1.0 x 10^9/L; AST </= 2.5 x ULN; ALT </= 2.5 x ULN
8) Continued from Inclusion #7: Total bilirubin </=1.5 x ULN, except in subjects with congenital bilirubinemia, such as Gilbert syndrome; Calculated creatinine clearance >/= 20 mL/min; Corrected serum calcium < 14 mg/dL (< 3.5 mmol/L); or free ionized calcium < 6.5 mg/dL (< 1.6 mmol/L); Platelet count >/= 70 x 10^9/L
9) Female subjects must be postmenopausal (at least 12 months since last menses), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before study entry, for the duration of study participation, and for 6 months after the last administration of study agent, and must have a negative serum or urine pregnancy test within 1 wk before beginning treatment. Men must be sterilized or agree to use a double-barrier method of birth control and must agree to not donate sperm during the study and for 6 months after the last administration of study agent.
10) Subjects must be able to adhere to study visit schedule and all protocol requirements
11) The anticipated life expectancy is such that the subject will be able to participate for the duration of the study
1) Diagnosis of primary amyloidosis, asymptomatic or smoldering multiple
myeloma or monoclonal gammopathy of undetermined significance (MGUS).
Smoldering multiple myeloma is defined as asymptomatic multiple myeloma
with absence of related organ or tissue impairment (ROTI) end-organ
damage). MGUS is defined by presence of serum M-protein < 3 g/dL;
absence of lytic bone lesions, anemia, hypercalcemia, and renal
insufficiency related to the M-protein; and (if determined) proportion
of plasma cells in the bone marrow of 10% or less.
2) Diagnosis of Waldenström’s disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
3) Prior or current systemic therapy or stem cell transplantation for multiple myeloma with the exception of emergency use of a short course (maximum 4 days) of corticosteroids before treatment.
4) Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0
5) Radiation therapy within 14 days before treatment
6) Plasmapheresis within 14 days before treatment
7) Major surgery within 14 days before treatment (Kyphoplasty is not considered major surgery)
8) Transplanted solid organ, with the exception of a corneal transplant (>/= 3 months before treatment)
9) History of allergic reaction or hypersensitivity to boron or mannitol, or known allergies or clinically significant reactions to murine, chimeric, or human proteins
10) Concurrent medical condition or disease (eg, active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
11) Serious concurrent illness or history of uncontrolled heart disease such as unstable angina, congestive heart failure, myocardial infarction within preceding 12 months, or clinically significant rhythm or conduction abnormality
12) Prior or concomitant malignancy (other than multiple myeloma) except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, localized prostate adenocarcinoma diagnosed >/= 3 years and without evidence of biochemical failure, or other cancer for which the subject has undergone potentially curative therapy and has no evidence of that disease for >/= 5 years.
13) Vaccinated with live, attenuated vaccines within 4 weeks of the first administration of CNTO 328
14) Known infection with HIV, known hepatitis C infection, or known to be hepatitis B surface antigen positive
15) Use of any investigational agents within 30 days or 5 half-lives (whichever is longer) of treatment
16) Pregnant or lactating women