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Trial record 96 of 107 for:    "Vascular Hemostatic Disease" | "Doxorubicin"

Velcade (Bortezomib), Adriamycin Dexamethasone (PAD) or Vincristine Adriamycin Dexamethasone in Second Line Treatment of Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00441168
Recruitment Status : Terminated (TRIAL STOPPED due to a change in standard of care and the required patient numbers could no longer be achieved)
First Posted : February 28, 2007
Results First Posted : March 21, 2014
Last Update Posted : March 21, 2014
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV

Tracking Information
First Submitted Date  ICMJE February 27, 2007
First Posted Date  ICMJE February 28, 2007
Results First Submitted Date  ICMJE December 3, 2009
Results First Posted Date  ICMJE March 21, 2014
Last Update Posted Date March 21, 2014
Study Start Date  ICMJE December 2006
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2014)
  • Best Confirmed Disease Response [ Time Frame: every 28 days during treatment period for up to 6 to 8 cycles ]
    The primary efficacy analysis was based on the best response obtained during the treatment period according to the European Group for Blood and Marrow Transplantation (EBMT) criteria as assessed by the investigator. The best confirmed response was defined as 2 separate and consecutive evaluations of response, at least 6 weeks apart (for progressive disease [PD], 1 to 3 weeks apart). The ordering of the responses was: complete response (CR), partial response (PR), minimal response (MR), no change (NC) and PD. CR was the best response and the poorest response was PD.
  • Best Reported Disease Response [ Time Frame: every 28 days during treatment period for up to 6 to 8 cycles ]
    The primary efficacy analysis was based on the best response obtained during the treatment period according to the EBMT criteria as assessed by the investigator. The ordering of the responses was: CR, PR, MR, NC and PD. CR was the best response and the poorest response was PD.
Original Primary Outcome Measures  ICMJE
 (submitted: February 27, 2007)
  • Safety and efficacy of replacing vincristine with Bortezomib in VAD
  • Main efficacy criterion is based on best response obtained during treatment. To have a response, the patient should have Complete Response or Partial Response as defined by EBMT criteria
Change History Complete list of historical versions of study NCT00441168 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2014)
Duration of Response (DOR) [ Time Frame: every 28 days during treatment period for up to 6 to 8 cycles ]
DOR was defined as the duration from the date of the best confirmed response for subjects who achieved CR or PR to the date of first documented evidence of PD (or relapse for subjects who experienced CR) over the duration of the study. DOR = ([Date of PD or date of censoring - Date of best response]+1)/30.44.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2007)
Secondary objectives are to assess duration of response, event free survival, time to progression, one year survival and overall survival.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Velcade (Bortezomib), Adriamycin Dexamethasone (PAD) or Vincristine Adriamycin Dexamethasone in Second Line Treatment of Multiple Myeloma
Official Title  ICMJE A Phase 2, Multicentre, Randomised, Open-Label, Parallel Group Study to Evaluate the Safety and Efficacy of Velcade When Added to Adriamycin-Dexamethasone Treatment Versus Vincristine-Adriamycin-Dexamethasone Standard Treatment in Subjects With Multiple Myeloma Who Are Refractory to or Have Relapsed After Primary Therapy for Multiple Myeloma
Brief Summary The purpose of this research study is to test the safety and effectiveness of replacing vincristine with a drug called bortezomib (also known as "Velcade"or PS341) in the standard therapy vincristine, doxorubicin (not limited to, but formerly referred to under the tradename Adriamycin) and dexamethasone (VAD) in patients with multiple myeloma. Multiple Myeloma is the second most common cancer of the blood. Bortezomib is the first approved cancer treatment in a new class of medicines called proteasome inhibitors. It disrupts the cell cycle of the cell, affecting numerous biologic pathways, including those related to growth and survival of cancer cells. The treatment will be used as second line treatment, which means either the disease has returned after a period of improvement (relapse) or the disease did not respond to the initial treatment (refractory). Patients will receive either bortezomib (PS341), doxorubicin (Adriamycin) and dexamethasone (PAD) or the VAD standard therapy.
Detailed Description Bortezomib, has been approved for use in patients with multiple myeloma, who have already received at least one prior treatment and whose disease is worsening on their last treatment and who have already undergone or are unsuitable for bone marrow transplantation. Bortezomib has significant activity in patients with relapsed multiple myeloma, its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin. The VAD combination has been widely used in multiple myeloma and has demonstrated to be effective in relapsed patients. Based on previous trial results, it is hoped that bortezomib, in replacing vincristine in the VAD standard therapy, can improve the response to treatment of patients with multiple myeloma, with manageable side effects. This is an international, multicentre, randomised, open-label, parallel group study. About 212 patients will take part in the study. Patients will be treated with either bortezomib (PS-341), Adriamycin and Dexamethasone (PAD) or Vincristine, Adriamycin and Dexamethasone (VAD). There will be an initial 14 day screening period to evaluate if the patient is suitable for the study. After screening, eligible patients will be randomised to receive either PAD or VAD. Patients will receive therapy for up to 8 treatment cycles of 28 days each. After the treatment period, there will be a long-term follow-up period with monthly visits until disease progression or relapse. Thereafter follow-up will be continued by at least a phone call every other month. This long-term follow-up period will be performed for all patients until the last patient was treated and followed up for 1 year. Response to treatment will be assessed according to the European group for blood and marrow transplant criteria (EBMT). Disease burden will be monitored by measuring M-protein concentration in serum and in urine every 4 weeks until disease progression or relapse. Thereafter follow-up for survival will be continued every other month by at least a phone call. Safety will be assessed by monitoring of adverse events (AEs), vital signs, physical examination and clinical laboratory tests. Treatment with PAD or VAD will be for up to 8 cycles of 28 days each. Treatment beyond 6 cycles will be discussed on individual basis. Proposed dosages are: bortezomib 1.3 mg/m² intravenous (IV) bolus on Days 1, 4, 8, and 11; vincristine 0.4mg IV push on Days 1 to 4; doxorubicin 9mg/m² IV push on Days 1 to 4; dexamethasone in 1st cycle 40 mg daily on Days 1 to 4, 9 to 12 and 17 to 20, orally (or equivalent parenteral dose) and on subsequent cycles as 40 mg daily on Days 1 to 4 and 17 to 20 only.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: adriamycin
    adriamycin: 9mg/m² intravenous (IV) push on days 1 to 4
  • Drug: bortezomib
    bortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11
  • Drug: dexamethasone
    dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle
  • Drug: vincristine
    vincristine: 0.4mg IV push on days 1 to 4
Study Arms  ICMJE
  • Active Comparator: VAD Treatment
    vincristine in combination with adriamycin and dexamethasone
    Interventions:
    • Drug: adriamycin
    • Drug: dexamethasone
    • Drug: vincristine
  • Experimental: PAD Treatment
    bortezomib in combination with adriamycin and dexamethasone
    Interventions:
    • Drug: adriamycin
    • Drug: bortezomib
    • Drug: dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 21, 2009)
30
Original Enrollment  ICMJE
 (submitted: February 27, 2007)
212
Actual Study Completion Date  ICMJE January 2008
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Relapsed or refractory multiple myeloma following 1 previous line of therapy and, is scheduled by the investigator to be treated with vincristine, adriamycin and dexamethasone standard therapy
  • measurable secretory multiple myeloma based on defined criteria
  • Karnofsky performance status of >or = 60%
  • fulfils defined laboratory requirements within 14 days before baseline
  • if female, the patient is either postmenopausal or surgically sterilised or willing to use an acceptable method of birth control for defined period of time
  • if male, the patient agrees to use an acceptable barrier method for contraception for a defined period of time.

Exclusion Criteria:

  • More than one previous line of therapy for multiple myeloma
  • use of bortezomib in the previous line of therapy and/or received bortezomib in a previous trial
  • known allergy or hypersensitivity to bortezomib, boron or mannitol
  • peripheral neuropathy or neuropathic pain of grade 2 or higher
  • myocardial infarction within 6 months of enrollment or had New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Croatia,   Germany,   Hungary,   Lithuania,   Poland,   Russian Federation,   Turkey
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00441168
Other Study ID Numbers  ICMJE CR011065
26866138MMY2038 ( Other Identifier: Janssen-Cilag International NV )
2006-001709-27 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen-Cilag International NV
Study Sponsor  ICMJE Janssen-Cilag International NV
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen-Cilag International NV Clinical Trial Janssen-Cilag International NV
PRS Account Janssen-Cilag International NV
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP