Study of DOXIL/CAELYX (Pegylated Liposomal Doxorubicin) and VELCADE (Bortezomib) or VELCADE Monotherapy for the Treatment of Relapsed Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00103506
First received: February 9, 2005
Last updated: May 8, 2015
Last verified: May 2015
  Purpose

The purpose of this study is to evaluate time to progression, overall survival, response rate and safety for the two open-label treatment groups; DOXIL/CAELYX in combination with VELCADE vs. VELCADE monotherapy.


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib (VELCADE)
Drug: Doxorubicin hydrochloride (DOXIL/CAELYX)
Phase 3

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 Controlled Study of DOXIL/CAELYX (Doxorubicin HCL Liposome Injection) and VELCADE (Bortezomib) or VELCADE Monotherapy for the Treatment of Relapsed Multiple Myeloma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Time to Progression (TTP) [ Time Frame: From date of first participant randomization (20 December 2004) up to interim analysis cut-off date (28 April 2006) ] [ Designated as safety issue: No ]
    Median time to progression of disease is assessed according to International Myeloma Working Group (IMWG) criteria or death from any cause. IMWG criteria: increase of >=25% from lowest level in Serum M-component or (the absolute increase must be >=0.5 gram per deciliter [g/dL]); Urine M component or (the absolute increase must be >=200 milligram per 24 hour. Only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase >10 mg/dL. Bone marrow plasma cell percentage >=10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing. Development of hypercalcemia. Participants who died or dropped out due to any reason without progression will be censored with the day of death or drop-out, respectively and who are alive at the end of the study without any progression was censored with the last available date.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From date of first participant randomization (20 December 2004) to cut-off date for final survival analysis (16 May 2014) ] [ Designated as safety issue: No ]
    The OS is defined as the time from the date of first dose of study drug to date of death from any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive.

  • Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: From date of first participant randomization (20 December 2004) to cut-off date for safety update (28 November 2006) ] [ Designated as safety issue: No ]

Enrollment: 646
Study Start Date: December 2004
Study Completion Date: June 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: VELCADE (bortezomib) monotherapy
Bortezomib (VELCADE) 1.3 mg/m2 by rapid (bolus) i.v. administration given on Days 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles.
Drug: Bortezomib (VELCADE)
1.3 mg/m2 by rapid (bolus) i.v. administration given on Days 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles.
Experimental: DOXIL/CAELYX in combination with VELCADE (bortezomib)
Bortezomib (VELCADE) 1.3 mg/m2 by rapid (bolus) i.v. administration given on Days 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles. Doxorubicin hydrochloride (DOXIL/CAELYX) 30 mg/m2 by i.v. infusion will be given on Day 4 of every 21-day cycle after the administration of bortezomib (VELCADE) for up to 8 cycles.
Drug: Bortezomib (VELCADE)
1.3 mg/m2 by rapid (bolus) i.v. administration given on Days 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles..
Drug: Doxorubicin hydrochloride (DOXIL/CAELYX)
30 mg/m2 by i.v. infusion will be given on Day 4 of every 21-day cycle after the administration of bortezomib (VELCADE) for up to 8 cycles.

Detailed Description:

This is a randomized (study drug assigned by chance), parallel-group, open-label (all involved people know the identity of the intervention), multicenter study in 18 countries. A total of 646 patients with multiple myeloma whose disease has progressed after an initial response to at least 1 line of prior therapy or was refractory to initial treatment will be enrolled. The primary endpoint is time to progression (the interval between the date of randomization and the date of disease progression); secondary endpoints are overall survival (the interval between the date of randomization and the patient's death from any cause), response rate (the proportion of patients in the evaluable population who achieved a complete or partial response), and safety. Other study endpoints include patient reported outcomes and exploratory pharmacogenics (to identify genetic markers of response). Patients are assessed for efficacy and safety every 3 weeks until disease progression is documented or for up to 42 weeks from the start of the first dose of study drug. Patients, who do not progress after the 42-week period, are assessed every 6 weeks until disease progression is documented. Efficacy evaluations includes: serum protein electrophoresis, 24-hour urine collection for protein electrophoresis, skeletal survey (plain films), bone marrow biopsy and aspirate, clinical or radiologic assessment of plasmacytomas, and serum calcium. Responses and progressions are assessed objectively by a computer algorithm based on the EBMT criteria. Safety evaluations include adverse event reports, changes in clinical laboratory findings, and tests for cardiac function (multiple gated acquisition scan/echocardiogram and electrocardiogram). Group A: VELCADE monotherapy: VELCADE 1.3 mg/m2 to be administered by i.v. bolus on Days 1, 4, 8, and 11 of each 21-day cycle. Group B: DOXIL/VELCADE combination: treated with VELCADE at the same dose and schedule as specified in Group A. DOXIL/CAELYX 30 mg/m2 by intravenous infusion given on Day 4 of every 21-day cycle following the administration of VELCADE.

  Eligibility

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

Inclusion Criteria:

  • Patients with multiple myeloma who have received at least 1 prior therapy and who have either responded and later had progressive disease or have progressed during their first therapy (primary refractory) are eligible for the study
  • Patients who may have received prior doxorubicin but not more than a cumulative dose of 240 mg/m2 doxorubicin, DOXIL, or the equivalent amount of another anthracycline (i.e., 1 mg doxorubicin = 1 mg DOXIL/CAELYX = 1.8 mg epirubicin = 0.3 mg mitoxantrone = 0.25 mg idarubicin)
  • Must have normal cardiac function, as evidenced by a left LVEF within institutional normal limits.

Exclusion Criteria:

  • History of treatment with VELCADE or progressive disease while receiving an anthracycline-containing regimen
  • No change in disease status during initial therapy
  • No treatment for malignancy within past 5 yrs (other than multiple myeloma) or progressive disease while receiving anthracycline-containing regimen
  • Non-secretory disease
  • Myocardial infarct within past 6 months
  • No major surgery in past 30 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00103506

  Show 109 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC C. Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided by Janssen Research & Development, LLC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT00103506     History of Changes
Other Study ID Numbers: CR004117, DOXILMMY3001, 2004-001842-34
Study First Received: February 9, 2005
Results First Received: May 8, 2015
Last Updated: May 8, 2015
Health Authority: United States: Food and Drug Administration
Great Britain: Medicines and Healthcare Products Regulatory Agency
Great Britain: Research Ethics Committee

Keywords provided by Janssen Research & Development, LLC:
Multiple Myeloma
Doxil
Caelyx
Doxorubicin
Velcade
Bortezomib

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Bortezomib
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on July 01, 2015