A Study to Compare CNTO 328 (Anti-IL-6 Monoclonal Antibody) and VELCADE-Melphalan-Prednisone (VMP) With VMP Alone in Previously Untreated Multiple Myeloma Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00911859
First received: May 29, 2009
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to evaluate safety and effectiveness of CNTO 328 when it is administered together with velcade-melphalan-prednisone (VMP) in comparison with VMP alone in patients with multiple myeloma (a type of cancer that affects the blood and bone marrow).


Condition Intervention Phase
Multiple Myeloma
Drug: CNTO 328
Drug: Bortezomib (Velcade)
Drug: Melphalan
Drug: Prednisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Number of patients with adverse events in Part 1 [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
  • Rate of Complete Response in Part 2 [ Time Frame: 54 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of patients who will achieve a confirmed Complete Response or Partial Response [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
  • Number of patients who will achieve stringent complete response (sCR) [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
    Stringent complete response (sCR) based on immunofixation + free light chain assay + either bone marrow immunohistochemistry or immunofluorescence. This will not to be performed after 12-month efficacy analysis.

  • Progression-free survival (PFS) [ Time Frame: From the date of inform consent signed up to end of study (death or disease progression whichever occurs first, as assessed up to approximately 3 years after the last patient will assigne to treatment in the study) ] [ Designated as safety issue: No ]
    PFS is defined as the time between randomization and either disease progression or death, whichever occurs first.

  • Duration of response [ Time Frame: 54 Weeks ] [ Designated as safety issue: No ]
    Duration of response is defined in patients with confirmed response (complete or partial response) as the time between first documentation of response and progressive disease (PD).

  • Number of patients who will alive at the end of Year 1 [ Time Frame: Year 1 ] [ Designated as safety issue: No ]
  • Number of patients who will alive at the end of Year 2 [ Time Frame: Year 2 ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: From the date of inform consent signed up to end of study (death or disease progression whichever occurs first, as assessed up to approximately 3 years after the last patient will assigne to treatment in the study) ] [ Designated as safety issue: No ]
    OS is defined as the time between randomization (Part 2) or the first administration of study agent (Part 1) and death.

  • Scores of Functional European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) for Part 2 [ Time Frame: Day 1 of each cycle of treatment and maintenance periods, 30 days after last dose of CNTO 328; Follow-up period: if discontinue treatment before Week 54, every 6 weeks until confirmed PD; if complete 9 cycles, every 9 weeks until confirmed PD ] [ Designated as safety issue: No ]
    The EORTC QLQ-C30 is use to measure the outcomes of cancer care and is consists of 30 items, attached with the questionnaire includes 9 multi-item scales (5 functional scales, 3 symptom scales, and a global health and quality of life scale) with other single item measures. The instrument contains 28 items using a Likert scale with 4 response options (Not at all, A Little, Quite a Bit, and Very Much) scored 1 to 4. Two additional items use response options 1 to 7 (1 = Very Poor, to 7 = Excellent). This will not to be performed after 12-month efficacy analysis.

  • Scores of Functional Assessment of Cancer Therapy/Gynecologic Oncology Group- Neurotoxicity (FACT/GOG-Ntx) for Part 2 [ Time Frame: Day 1 of each cycle of treatment and maintenance periods, 30 days after last dose of CNTO 328; Follow-up period: if discontinue treatment before Week 54, every 6 weeks until confirmed PD; if complete 9 cycles, every 9 weeks until confirmed PD ] [ Designated as safety issue: No ]
    The FACT/GOG-Ntx is to determine the presence and intensity of neuropathic pain or peripheral neuropathy to guide interventions and dose modifications. The instrument contains 10 items, notes symptoms and concerns associated with chemotherapy-induced neuropathy. Response options are based on a 5-point Likert scale, and use a 7-day recall period. This will not to be performed after 12-month efficacy analysis.

  • Number of patients with adverse events [ Time Frame: From the date of inform consent signed up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
  • Minimum observed serum concentration of CNTO 328 for Part 1 [ Time Frame: Day 1 and Day 22 ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Minimum observed serum concentration of CNTO 328 for Part 2 (Arm A) [ Time Frame: Days 1 and 22 of Cycles 1, 2, and 3 of treatment period; 30 days after last dose of CNTO 328; 3, 9, and 12 weeks after the last administration of CNTO 328 during the follow-up period ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Maximum observed serum concentration of CNTO 328 for Part 1 [ Time Frame: Day 1 and Day 22 ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Maximum observed serum concentration of CNTO 328 for Part 2 (Arm A) [ Time Frame: Days 1 and 22 of Cycles 1, 2, and 3 of treatment period; 30 days after last dose of CNTO 328; 3, 9, and 12 weeks after the last administration of CNTO 328 during the follow-up period ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Area under the serum concentration versus time curve for Part 1 [ Time Frame: Day 1 and Day 22 ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Area under the serum concentration versus time curve for Part 2 (Arm A) [ Time Frame: Days 1 and 22 of Cycles 1, 2, and 3 of treatment period; 30 days after last dose of CNTO 328; 3, 9, and 12 weeks after the last administration of CNTO 328 during the follow-up period ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Total systemic clearance of CNTO 328 for Part 1 [ Time Frame: Day 1 and Day 22 ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Total systemic clearance of CNTO 328 for Part 2 (Arm A) [ Time Frame: Days 1 and 22 of Cycles 1, 2, and 3 of treatment period; 30 days after last dose of CNTO 328; 3, 9, and 12 weeks after the last administration of CNTO 328 during the follow-up period ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Volume of distribution of CNTO 328 for Part 1 [ Time Frame: Day 1 and Day 22 ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Volume of distribution of CNTO 328 for Part 2 (Arm A) [ Time Frame: Days 1 and 22 of Cycles 1, 2, and 3 of treatment period; 30 days after last dose of CNTO 328; 3, 9, and 12 weeks after the last administration of CNTO 328 during the follow-up period ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Serum antibodies to CNTO 328 for Part 1 [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Serum antibodies to CNTO 328 for Part 2 (Arm A) [ Time Frame: Days 1 and 22 of Cycles 1, 2, and 3 of treatment period; 30 days after last dose of CNTO 328; 3, 9, and 12 weeks after the last administration of CNTO 328 during the follow-up period ] [ Designated as safety issue: No ]
    This analysis will not to be performed after 12-month effectiveness analysis.

  • Serum level of interleukin-6 (IL-6; Target-associated markers): bioactive and total for Part 2 (Arm A) [ Time Frame: Days 1, 4, 8, 22 of Cycle 1 and Days 1, 4 of Cycles 2, 3, 4 of the treatment period ] [ Designated as safety issue: No ]
    IL-6 is a pleiotropic cytokine that plays a major role in inflammatory processes.

  • Serum level of C-reactive protein (CRP; inflammation-associated markers) for Part 1 [ Time Frame: Day 1, Day 4, Day 8, Day 22 ] [ Designated as safety issue: No ]
  • Serum level of C-reactive protein (CRP; inflammation-associated markers) for Part 2 [ Time Frame: Days 1, 4, 8, 22 of Cycle 1 and Days 1, 4 of Cycles 2, 3, 4 of the treatment period ] [ Designated as safety issue: No ]
  • Serum level of syndecan-1 (prognostic markers) for Part 2 [ Time Frame: Days 1, 4, 8, 22 of Cycle 1 and Days 1, 4 of Cycles 2, 3, 4 of the treatment period ] [ Designated as safety issue: No ]
  • Serum level of hepcidin (iron metabolism markers ) for Part 2 [ Time Frame: Days 1, 4, 8, 22 of Cycle 1 and Days 1, 4 of Cycles 2, 3, 4 of the treatment period ] [ Designated as safety issue: No ]
  • Serum level of bone-related markers for Part 2 [ Time Frame: Days 1, 4, 8, 22 of Cycle 1 and Days 1, 4 of Cycles 2, 3, 4 of the treatment period ] [ Designated as safety issue: No ]

Enrollment: 118
Study Start Date: June 2009
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CNTO 328 + VMP
The patients will receive CNTO 328 11 mg/kg (part 1) and 8.3 mg/kg or 11 mg/kg (Part 2) as a 1 hour infusion every three weeks with VELCADE + Melphalan + Prednisone (VMP) for 9 cycles of treatment period and maintenance period in Part 2 (Arm A).
Drug: CNTO 328
CNTO 328 8.3 mg/kg or 11 mg/kg will be administered intravenously every 3 weeks for each 9 cycles of treatment period and maintenance period in Part 2 (Arm A).
Drug: Bortezomib (Velcade)
Patients will receive bortezomib according to currently approved package inserts. Bortezomib 1.3 mg/m2 will be administered intravenously in Part 1 and for 9 cycles of the treatment period in Part 2 (Arm A + Arm B). It will be administered twice weekly for first 4 cycles (on Days 1, 4, 8, 11, 22, 25, 29, and 32, followed by a 10-day rest period) and once weekly for next 5 cycles (on Days 1, 8, 22, and 29, followed by a 13-day rest period).
Drug: Melphalan
Patients will receive melphalan according to currently approved package inserts. Melphalan 9 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1 and for 9 cycles of treatment period in Part 2 (Arm A + Arm B).
Drug: Prednisone
Patients will receive prednisone according to currently approved package inserts. Prednisone 60 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1 and for 9 cycles of treatment period in Part 2 (Arm A + Arm B).
Active Comparator: VMP
Patients will receive VMP alone in Part 2 (Arm B) according to currently approved package inserts for 9 cycles.
Drug: Bortezomib (Velcade)
Patients will receive bortezomib according to currently approved package inserts. Bortezomib 1.3 mg/m2 will be administered intravenously in Part 1 and for 9 cycles of the treatment period in Part 2 (Arm A + Arm B). It will be administered twice weekly for first 4 cycles (on Days 1, 4, 8, 11, 22, 25, 29, and 32, followed by a 10-day rest period) and once weekly for next 5 cycles (on Days 1, 8, 22, and 29, followed by a 13-day rest period).
Drug: Melphalan
Patients will receive melphalan according to currently approved package inserts. Melphalan 9 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1 and for 9 cycles of treatment period in Part 2 (Arm A + Arm B).
Drug: Prednisone
Patients will receive prednisone according to currently approved package inserts. Prednisone 60 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1 and for 9 cycles of treatment period in Part 2 (Arm A + Arm B).

Detailed Description:

The study will be conducted in 2 parts (Part 1 and Part 2) and will consist of screening period up to 2 weeks; treatment period; maintenance period (CNTO 328) for a maximum of 18 months and follow up period until the study ends. Part 1 is an open-label (all people know the identity of the intervention), single group safety lead-in part to evaluate the safety of CNTO 328. Approximately 12 patients will be treated with CNTO 328 in combination with VMP. If the safety profile of the combination is acceptable, the study will proceed to Part 2. Part 2 is a randomized (the study medication is assigned by chance), open-label, 2-arm (Arm A: CNTO 328 + VMP; Arm B: VMP alone) study. Approximately 104 patients will be equally randomized, followed by a maintenance period with CNTO 328 in patients in Arm A who achieve a partial response (PR) or better. Patients in both parts of the study will be treated up to a maximum of nine 6-weeks cycles provided there is no evidence of disease progression, unacceptable toxicity, or withdrawal from treatment. Study medication will be continued for at least 2 additional cycles after confirmation of complete response, and preferably for the full 9 cycles of the treatment period. Patients who will be receiving maintenance treatment after the 12-month effectiveness analysis may continue to receive treatment with CNTO 328 only after careful consideration by the treating physician and on evidence of clinical benefit and in the absence of unwarranted toxicities. Safety assessments will include evaluation of adverse events, clinical laboratory tests, eastern cooperative oncology group performance status, electrocardiogram, vital signs, and physical examination which will be monitored throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of previously untreated multiple myeloma and not a candidate for high dose chemotherapy with stem cell transplantation
  • Eastern cooperative oncology group performance status score of less than or equal to 2
  • Measurable secretory disease, defined as either serum monoclonal paraprotein greater than or equal to 1 g/dL or urine monoclonal protein greater than 200 mg/24 hours
  • Adequate laboratory results that will be confirmed by a study physician
  • Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

  • Diagnosed with primary amyloidosis, asymptomatic or smoldering multiple myeloma or monoclonal gammopathy of undetermined significance
  • Diagnosed with Waldenstrom'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
  • Received prior or current systemic therapy or stem cell transplantation for multiple myeloma
  • Peripheral neuropathy or neuropathic pain (Grade 2 or higher)
  • Received radiation therapy, plasmapheresis or surgery within 14 days
  • Transplanted solid organ, with the exception of a corneal transplant
  • Serious concurrent illness or history of uncontrolled heart disease
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00911859

  Show 37 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development L.L.C Clinical Trial Janssen Research & Development L.L.C
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT00911859     History of Changes
Obsolete Identifiers: NCT01710241
Other Study ID Numbers: CR015901, CNTO328MMY2001, 2008 007157 12
Study First Received: May 29, 2009
Last Updated: March 3, 2014
Health Authority: Italy: Ministry of Health
United States: Food and Drug Administration
United States: Federal Government

Keywords provided by Janssen Research & Development, LLC:
Multiple Myeloma
CNTO328
Interleukin-6 (IL-6)
Monoclonal antibody
Anti-IL-6 monoclonal antibody
Bortezomib
Velcade
Melphalan
Prednisone

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Antibodies, Monoclonal
Melphalan
Bortezomib
Prednisone
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Myeloablative Agonists
Immunosuppressive Agents
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Glucocorticoids

ClinicalTrials.gov processed this record on April 22, 2014