An Efficacy and Safety Study of Bortezomib Re-treatment in Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV
ClinicalTrials.gov Identifier:
NCT00431769
First received: February 2, 2007
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to evaluate the safety and efficacy of bortezomib in participants with multiple myeloma who have previously responded to a bortezomib based therapy.


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Open-Label Trial Using Velcade for ReTreatment of Multiple Myeloma Subjects Following an Initial Response to Velcade

Resource links provided by NLM:


Further study details as provided by Janssen-Cilag International NV:

Primary Outcome Measures:
  • Best Confirmed Response to Bortezomib Re-Treatment [ Time Frame: Day 1 of every alternate cycle starting from Cycle 1 up to End of Treatment (30 to 42 days after last dose administration of bortezomib) ] [ Designated as safety issue: No ]
    Number of participants with best confirmed response to bortezomib Re-Treatment will be assessed by the European Group for Blood and Marrow Transplantation (EBMT) criteria. Best confirmed response is, if administration of bortezomib provide continuing or additional clinical benefit after previous bortezomib administration. The ordering of possible responses are Complete Response (CR), Partial Response (PR), Minimal Response (MR), No Change (NC) and Progressive Disease (PD)/relapse from CR. CR is the best response and the poorest response is PD or relapse from CR.


Secondary Outcome Measures:
  • Participants With Percent Change in Baseline Serum Monoclonal Protein (M-protein) Best Confirmed Response Category [ Time Frame: Day 1 of every alternate cycle starting from Cycle 1 up to End of Treatment (30 to 42 days after last dose administration of bortezomib) ] [ Designated as safety issue: No ]
    Number of participants with percent change in baseline serum M-protein best confirmed response category will be assessed by EBMT criteria. Best confirmed response is, if administration of bortezomib provide continuing or additional clinical benefit after previous bortezomib administration. Decrease in serum M-protein levels from baseline represents improvement. Participants having baseline M-protein value of <5 gram per liter (g/L) (serum) or <200 mg/24 hour (urine) will be classed in 'Not Evaluable' category and any response rate (RR) which is unconfirmed will be classed as 'Missing'.

  • Participants with Percent Change in Baseline Urine Monoclonal Protein (M-protein) Best Confirmed Response Category [ Time Frame: Day 1 of every alternate cycle starting from Cycle 1 up to End of Treatment (30 to 42 days after last dose administration of bortezomib) ] [ Designated as safety issue: No ]
    Number of participants with percent change in baseline Urine M-protein best confirmed response category will be assessed by EBMT criteria. According to EBMT best confirmed response is, if administration of bortezomib provide continuing or additional clinical benefit after previous bortezomib administration. Decrease in urine M-protein levels from baseline represents improvement. Participants having baseline M-protein value of <5 g/L (serum) or <200 mg/24 hour(urine) will be classed in 'Not Evaluable' category and any RR which is unconfirmed will be classed as 'Missing'.

  • Duration of Best Confirmed Response (DOR) [ Time Frame: Day 1 Cycle 1 up to last follow-up visit (8 weeks until PD) ] [ Designated as safety issue: No ]
    The DOR is defined as the duration (months) from the date of the first evidence of a best confirmed response to the date of first documented evidence of PD (or relapse for participants who experienced CR). The PD or relapse are defined as one or more of following criteria: >25% increase in either serum or urine M-protein, >25% increase in plasma cells on bone marrow, Definite increase in size of bone lesion or plasmacytoma, Development of new bone lesion or plasmacytoma, Development of hypercalcaemia. The DOR will be calculated separately in participants with a best confirmed response of >=PR.

  • Time to Progression (TTP) for Best Confirmed Response [ Time Frame: (Day 1 Cycle 1 up to last follow-up visit date (8 weeks until PD) ] [ Designated as safety issue: No ]
    The TTP is defined as the duration (in months) from the date of first study treatment administration (enrollment at Day 1, Cycle 1) until the date of first documented evidence of PD (or relapse for participants who experienced CR). PD or relapse are defined as one or more of the following criteria: ->25% increase in either serum or urine M-protein. ->25% increase in plasma cells on bone marrow. -Definite increase in size of bone lesion or plasmacytoma. -Development of new bone lesion or plasmacytoma. -Development of hypercalcaemia


Enrollment: 130
Study Start Date: June 2006
Study Completion Date: January 2010
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib Drug: Bortezomib
Bortezomib will be given intravenously (into a vein) twice weekly, on Days 1, 4, 8 and 11 and then a 10-day (Days 12 to 21) rest period, of each 3-week cycle for up to a total of 8 cycles. The initial bortezomib dose is 1.0 or 1.3 milligram per meter square (mg/m^2) depending on the previous bortezomib-based treatment, up to a maximum dose of 1.3 mg/m^2. Participants will receive bortezomib in combination with or without dexamethasone, in accordance with the standard of care. The median total dose of dexamethasone per cycle ranges from 120 mg (Cycle 7) to 160 mg (Cycles 1 to 6 and 8).

Detailed Description:

This is an Open-Label (all people know the identity of the intervention), non-randomized, multicenter (when more than one hospital or medical school team work on a medical research study), single arm study to evaluate the safety and efficacy of bortezomib in participants with multiple myeloma (cancer of the types of cells normally found in bone marrow) who have previously responded to a bortezomib based therapy. Participants will be non-randomly assigned to single group bortezomib. Participants will be treated with bortezomib alone or in combination with another drug (dexamethasone). Bortezomib will be given intravenously (i.v. [into a vein]) twice Weekly, on Days 1, 4, 8 and 11 of each cycle followed by a 10-day (Days 12 to 21) rest period. The total duration of treatment period will be 8 cycles, each lasting 3 weeks. The initial bortezomib dose is the last tolerated dose (1.0 or 1.3 milligram per metersquare [mg/ m^2] on the previous bortezomib-based treatment. Participants who start the study on a dose of 1.0 mg/m^2 bortezomib and tolerate the dose well could have their dose escalated to 1.3 mg/m^2. Doses above 1.3 mg/m^2 are not allowed. A complete cycle comprises 4 doses of bortezomib. Dexamethasone will be first introduced in Cycles 1 to 5 (i.e.dexamethasone will not be introduced for the first time in Cycles 6 to 8). The median total dose of dexamethasone received per cycle ranges from 120 mg (cycle 7) to 160 mg (cycles 1 to 6 and 8). Efficacy will be primarily assessed by determining Best Confirmed Response according to the European Group for Blood and Marrow Transplantation (EBMT) criteria. Participant's safety 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:

  • Participant was previously diagnosed with multiple myeloma based on standard criteria and had measurable disease. Measurable disease for secretory multiple myeloma was defined as any quantifiable serum M-protein value (generally, but not exclusively, greater than (>) 1 gram per deciliter (g/dL) immunoglobulin (Ig) G Myeloma protein (M-protein) and >0.5 g/dL Ig A) or urine light-chain excretion of equal to (=) or >200 milligram (mg)/24 hour
  • Participant previously tolerated 1.0 or 1.3 mg/metersquare (m^2) bortezomib alone or in combination with other agents and had complete response (CR) or partial response (PR) upon completion of bortezomib therapy
  • It had been greater than or equal to (>=) 6 months since the participant's last bortezomibdose and the participant had progressive disease (PD) if prior response to bortezomib was PR or the participant had relapsed from CR
  • Participant had a life expectancy >3 months
  • If female, the participant was either postmenopausal or surgically sterilized or willing to use an acceptable method of birth control from screening through at least 30 days after completion of the last cycle

Exclusion Criteria:

  • Participant had received chemotherapy, radiotherapy, antibody, immunotherapy, or experimental therapy to treat multiple myeloma since their last dose of bortezomib. Note: participants could have received localized palliative radiotherapy for complications due to osteolytic bone lesions. Participants could have received steroids (dexamethasone or equivalent) or thalidomide or interferon as maintenance therapy since their last dose of bortezomib according to local standard of care. In addition, participants could have received a cumulative dose of up to 160 mg dexamethasone or equivalent as emergency therapy within 4 weeks prior to enrolment. Participants could have received high dose therapy/stem cell transplantation after induction regimen containing bortezomib, but only if PR or CR was observed during bortezomib containing induction therapy
  • Participant had uncontrolled or severe cardiovascular disease, including myocardial infarction within 6 months of enrolment or had New York Heart Association Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Participant had poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to the protocol
  • Participant had another malignancy within the past 5 years. Exceptions were made for the following if they were treated and not active: basal cell or non-metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or International Federation of Gynecology and Obstetrics Stage 1 carcinoma of the cervix
  • Patient has an uncontrolled or severe cardiovascular disease, within 6 months of enrolment
  • Female participant was pregnant or breast feeding. Confirmation that the participant was not pregnant was to be established by a negative beta human chorionic gonadotropin pregnancy test result obtained during the Screening period. Pregnancy testing was not required for post menopausal or surgically sterilized women.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00431769

  Show 39 Study Locations
Sponsors and Collaborators
Janssen-Cilag International NV
Investigators
Study Director: Janssen-Cilag International NV Clinical Trial Janssen-Cilag International NV
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT00431769     History of Changes
Other Study ID Numbers: CR010519, 26866138MMY2036, 2005-005819-26
Study First Received: February 2, 2007
Last Updated: May 9, 2014
Health Authority: Belgium: Ministry of Social Affairs, Public Health and the Environment
Germany: Ethics Commission
Austria: Agency for Health and Food Safety
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ministry of Health
Greece: Ministry of Health and Welfare
Italy: Ministry of Health
Portugal: Ethics Committee for Clinical Research
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Janssen-Cilag International NV:
Multiple myeloma
Bortezomib
Dexamethasone
VELCADE

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
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014