Clinical Trial: Treatment With Velcade (Bortezomib) Plus Dexamethasone (VD) or VD Plus Cyclophosphamide or VD Plus Lenalidomide in Patients With Multiple Myeloma Stabilized After 4 Cycles of VD

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Efficacy and Safety of Velcade Plus Dexamethasone (VD), VD+Cyclophosphamide or VD Plus Lenalidomide in MMY Patients Who Are Refractory or Have Relapsed After Their Primary Therapy for MMY and Have Ach

Brief Summary: The purpose of this study is to test the effectiveness and safety of adding cyclophosphamide or lenalidomide to the VD combination in the treatment of patients with multiple myeloma that have achieved a stable response after 4 initial cycles of treatment with VD. Multiple myeloma is the second most common cancer of the blood. Bortezomib disrupts the life cycle of the cell, affecting numerous biologic pathways, including those related to growth and survival of cancer cells.

Detailed Summary:

It has been shown that quality of response corresponds with clinical benefit. Stable disease is not regarded as a satisfactory result of therapy for relapsed and refractory multiple myeloma. However, there is no consensus if, when and how treatment should be continued or changed in the case of stable disease.

There are different strategies of achieving an optimal quality of response in relapsed and refractory multiple myeloma. One is to treat for a longer duration with one regimen. The alternative path can be a sequential approach adding another agent to the initial regimen depending on the outcome of therapy after a defined treatment period. These two principles will be evaluated in the present study.

Both Cyclophosphamide and Lenalidomide have proven to be efficacious in multiple myeloma and combinations of both agents with bortezomib and Dexamethasone have been shown to be active and tolerable.

In this study patients with relapsed/progressive or refractory multiple myeloma will start treatment with bortezomiib and Dexamethasone. Response will be evaluated after four cycles. Patients with complete, very good partial response or partial response will continue treatment as initiated. Patients with stable disease will either continue treatment with the bortezomib/Dexamethasone combination for another four cycles or will receive Cyclophosphamide or Lenalidomide as an additional third agent for another four cycles.

Patients with multiple myeloma that are refractory to or have relapsed/progressed after primary treatment for multiple myeloma will be enrolled in the study. All patients will receive a combination of bortezomib plus dexamethasone for a total of four cycles. Based on the response to this treatment, further study trea
Sponsor: Janssen-Cilag International NV

Current Primary Outcome: Overall Best Confirmed Response [ Time Frame: Prior to treatment at day 1 of each cycle and at the end of treatment (day 21 of cycle 8), up to 168 days ]

Original Primary Outcome: Assessment of the efficacy of adding either Cyclophosphamide or Lenalidomide to the combination of VD. The efficacy response will be measured by the response rate of the disease as per IMWG 2006 criteria [ Time Frame: Response to therapy Day 1 of Cycle 1 (baseline), at Day 1 of all subsequent cycles, at the End of Treatment visit and at every Follow-up Visit (monthly) until there is evidence of Progressive Disease or relapse or until start of alternative MMY treatment ]

Current Secondary Outcome:

• Median Time to First Confirmed Response [ Time Frame: At Day 1 of each treatment cycle, at the End of Treatment visit until there is evidence of Progressive Disease or relapse from Complete Response (CR), up to 168 days ]
  Time from start of treatment to the date of the first documentation of a confirmed response. Estimated using the Kaplan-Meier method. Response was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria and validated by an Independent Monitoring Committee.
• Progression Free Survival [ Time Frame: At Day 1 of each treatment cycle, at the End of Treatment visit until there is evidence of Progressive Disease or relapse from Complete Response (CR). Median Follow-Up of 16.9 months ]
  Time from start of treatment to date of disease progression, relapse from CR or death. Estimated using the kaplan-meier method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions", or similar definition as accurate and appropriate.
• Time to Progression [ Time Frame: At Day 1 of each treatment cycle, at the End of Treatment visit until there is evidence of Progressive Disease or relapse from Complete Response (CR), Median Follow-up of 16.9 months ]
  Is calculated as the time from start of treatment to the date of the first observation of disease progression or relapse from CR. Deaths owing to causes other than progression not counted, but censored. Subjects who withdraw from the study or die will be censored at the time of last disease assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).
• One Year Survival [ Time Frame: At each visit from baseline to end of treatment. After treatment, monthly visit until progression or relapse or until the start of alternative MMY therapy, up to 1 year ]
  Percent Probability of Survival at 1 year from the start of treatment, estimated using Kaplan-Meier analysis.
• Overall Survival [ Time Frame: At each visit from baseline to end of treatment. After treatment, monthly visit until progression or relapse or until the start of alternative MMY therapy. Further follow up by monthly phone call until the last patient was treated and followed for 1 year ]
  Is defined as the time interval from start of treatment to the date of death due to any cause. In the absence of confirmation of death (including subjects lost to follow-up), survival time will be censored at the last date the subject is known to be alive

Original Secondary Outcome: Assessment of the Safety Profile and Additional Efficacy Parameters Including the Time to Response, Duration of Response, Progression Free Survival, the Time to Progression, the One Year Survival and the Overall Survival of the Patients [ Time Frame: Day 1 of each cycle, 30 days after last dose of study drug, monthly until relapse or Progressive Disease / SAEs: from informed consent signature until 30 days after last dose of study drug (when occurring after 30 days, reported if related to study drug) ]

Information By: Janssen-Cilag International NV

Dates:
Date Received: May 21, 2009
Date Started: May 2008
Date Completion:
Last Updated: January 14, 2015
Last Verified: January 2015