Back to resultsStudy of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
bendamustine
bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
The patient:
- has a diagnosis of multiple myeloma.
- currently has multiple myeloma with measurable disease.
- must have received at least 1 previous treatment regimen and shows signs of progressive disease at the time of study entry.
- if a woman of child bearing potential (not surgically sterile or at least 12 months naturally postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study.
- if a man, must agree to use an acceptable method of contraception throughout the study and for 90 days after last dose study drug.
- must have an Eastern Cooperative Oncology Group (ECOG) performance status not greater than 2.
- must have a life-expectancy of greater than 3 months.
- must meet specific protocol-related hematological and laboratory criteria within 14 days of enrollment.
Exclusion Criteria:
The patient has:
- had a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix).
- plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes (POEMS) syndrome.
- plasma cell leukemia.
- non-measurable multiple myeloma.
- Common Terminology Criteria for Adverse Events (CTCAE) grade 2 (or greater) peripheral neuropathy within 14 days before enrollment.
- previously participated in a Cephalon-sponsored clinical study with bendamustine.
- impaired cardiac function or clinically significant cardiac diseases.
- undergone major surgery within 4 weeks prior to screening or has not recovered from side effects of such therapy.
- severe hypercalcemia.
- other concurrent severe and/or uncontrolled medical or psychiatric conditions.
- known positivity for human immunodeficiency virus (HIV) or hepatitis B or C.
- a history of allergic reaction attributable to compounds of similar chemical or biological composition to bendamustine, bortezomib, boron, or mannitol.
- received chemotherapy within 3 weeks before enrollment, with the exception of nitrosoureas, which should be discontinued at least 6 weeks before enrollment.
- received corticosteroids (greater than 10 mg/day prednisone or equivalent) within 3 weeks before enrollment.
- received immunotherapy, antibody, or radiation therapy within 4 weeks before enrollment.
- a status as a pregnant or lactating woman. Any women becoming pregnant during the study will be withdrawn from the study.
- a status as a male whose sexual partner is a woman of childbearing potential not using effective birth control.
- used an investigational drug within 1 month before the screening visit.
Sites / Locations
- Pacific Oncololgy & Hematology
- Capitol Hematology Oncology
- University Of California, San Diego
- James R. Berenson, M.D., Inc.
- George Washington University
- Northshore University Health System
- Alivin & Lois Lapidus Cancer Institute
- Center for Cancer and Blood Disorders
- Sophia Gordon Cancer Center at Lahey Clinic
- Geisinger Medical Center
- Charleston Hematology Oncology, PA
- Family Cancer Center, PLLC
- Fairfax Northern Virginia Hematology Oncology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Bendamustine and Bortezomib
Arm Description
Bendamustine in escalating doses of 50, 70 or 90 mg/m^2 as combination therapy with bortezomib at 1.0 mg/m^2/dose administered for up to eight 28 day cycles.
Outcomes
Primary Outcome Measures
Participants With Dose Limiting Toxicity (DLT)
Maximum tolerated dose was the dose that was 1 step lower than the dose where at least one third of patients experienced DLT. A DLT was defined as any of the following occurring during the first cycle:
grade 4 hematologic toxicity without regard for relationship to study drug treatment
thrombocytopenia grade 3 with grade 3 or grade 4 hemorrhage
grade 3 febrile neutropenia
grade 3 or grade 4 nausea and vomiting refractory to anti emetic therapy
any study drug related grade 3 or grade 4 nonhematologic toxicity
any drug related death
Toxicity grades (3=severe AE and 4=life-threatening or disabling AE) were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.
Secondary Outcome Measures
Percentage of Participants With An Overall Tumor Response As Assessed By the Investigator
Overall tumor response is the sum of a complete response (CR), very good partial response (VGPR), partial response (PR) and minimal response (MR). A modified version of the Bladé criteria for response was used. Abbreviated definitions for the response categories can be found in the description of outcome #3.
Participants' Best Tumor Response as Assessed by the Investigator
Abbreviated criteria for response categories: CR includes the disappearance of the original monoclonal protein (M-protein) from blood and urine, and <5% plasma cells in the bone marrow, and no increase in size/number of lytic bone lesions, and disappearance of soft tissue plasmacytomas for >=4 weeks. VGPR includes serum and urine M-protein detectable by immunofixation but not electrophoresis, and reduction in 24-hr urinary light chain excretion by <100 mg, and disappearance of soft tissue plasmacytomas for >= 4 weeks, and no increase in size/number of lytic bone lesions. PR includes a >=50% reduction in serum M-protein, and reduction in 24-hr urinary light chain excretion by either >=90% or to <200 mg, and >=50% reduction in size of soft tissue plasmacytomas, and no increase in size/number of lytic bone lesions. MR includes a >=25% and <=49% reduction in serum M-protein. SD does not meet criteria for the other response categories. See outcome #4 for a definition of PD.
Kaplan-Meier Estimate for Time to Progression (TTP)
Time to progression was defined as the time from initiation of therapy to progressive disease (PD). PD requires at least one of the following:
>25% increase in serum monoclonal paraprotein (which must also be an absolute increase of at least 5 g/L),
>25% increase in 24-hour urinary light chain excretion (which must also be an absolute increase of at least 200 mg/24 h),
>25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy (which must also be an absolute increase of at least 10%),
definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas,
the development of new bone lesions or soft tissue plasmacytomas,
the development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).
Kaplan-Meier Estimate for Progression-Free Survival
Progression free survival is the time between the date of initiation of therapy to progressive disease (PD) or death from any cause, whichever occurs first. See outcome #4 for a definition of PD.
Time to the First Response
Time to first response is defined as the time from the initiation of therapy to the first evidence of a confirmed response (ie, CR, VGPR, PR, or MR).
Kaplan-Meier Estimate for Duration of Response
Duration of response (DR) is defined as the time from the first response to progressive disease (PD). See outcome #4 for a PD definition.
Kaplan-Meier Estimate for Overall Survival (OS)
Overall survival is defined as the time from initiation of therapy to death from any cause or last follow-up visit.
Summary of Participants With Adverse Events (AEs)
Counts of participants who had AEs are summarized in a variety of categories. Severity and relatedness to study drug are in the opinion of the investigator according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0. Severity is rated on a 5-point scale: 1=mild, 2=moderate, 3=severe, 4=life threatening or disabling, and 5= death related to AE. Relatedness is assessed on a 5-point scale: not related, unlikely, possible, probable and definite. Definite, probable and possible answers are reported as 'related' to study medication. Deaths are reported up to 18 months. All the deaths occurred beyond the treatment-emergent timeframe since they occurred 6.5-16 months after the final dosing. All other parts of the summary represent the treatment-emergent timeframe (up to 8.5 months) which is the treatment period plus 30 days.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00920855
Brief Title
Study of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma
Official Title
An Open-Label Study of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
June 2009 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
December 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cephalon
4. Oversight
5. Study Description
Brief Summary
The primary objective of this study is to assess the safety and tolerability of bendamustine as combination therapy with bortezomib for patients with relapsed/refractory multiple myeloma (MM).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bendamustine and Bortezomib
Arm Type
Experimental
Arm Description
Bendamustine in escalating doses of 50, 70 or 90 mg/m^2 as combination therapy with bortezomib at 1.0 mg/m^2/dose administered for up to eight 28 day cycles.
Intervention Type
Drug
Intervention Name(s)
bendamustine
Other Intervention Name(s)
CEP-18083, Bendamustine hydrochloride, TREANDA
Intervention Description
Bendamustine was administered to 3 cohorts of patients at escalating doses of 50 (cohort 1), 70 (cohort 2) and 90 mg/m^2/dose (cohort 3). Doses were administered by intravenous (iv) infusion once daily on days 1 and 4 of each 28-day cycle. Each iv was administered over 60 minutes and followed the injection of bortezomib.
Bortezomib will be administered to patients at a dose of 1.0 mg/m2/dose as an iv push over 3 to 5 seconds followed by a standard saline flush or through a running iv line. Doses are to be administered to patients on days 1, 4, 8 and 11 of the 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
VELCADE®
Intervention Description
Bortezomib was administered at a dose of 1.0 mg/m^2/dose as an intravenous (iv) push over 3 to 5 seconds followed by a standard saline flush or through a running iv line. Doses are to be administered on days 1, 4, 8 and 11 of each 28-day cycle.
Primary Outcome Measure Information:
Title
Participants With Dose Limiting Toxicity (DLT)
Description
Maximum tolerated dose was the dose that was 1 step lower than the dose where at least one third of patients experienced DLT. A DLT was defined as any of the following occurring during the first cycle:
grade 4 hematologic toxicity without regard for relationship to study drug treatment
thrombocytopenia grade 3 with grade 3 or grade 4 hemorrhage
grade 3 febrile neutropenia
grade 3 or grade 4 nausea and vomiting refractory to anti emetic therapy
any study drug related grade 3 or grade 4 nonhematologic toxicity
any drug related death
Toxicity grades (3=severe AE and 4=life-threatening or disabling AE) were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.
Time Frame
Day 1 - 28
Secondary Outcome Measure Information:
Title
Percentage of Participants With An Overall Tumor Response As Assessed By the Investigator
Description
Overall tumor response is the sum of a complete response (CR), very good partial response (VGPR), partial response (PR) and minimal response (MR). A modified version of the Bladé criteria for response was used. Abbreviated definitions for the response categories can be found in the description of outcome #3.
Time Frame
Up to 7.5 months (eight 28-day cycles)
Title
Participants' Best Tumor Response as Assessed by the Investigator
Description
Abbreviated criteria for response categories: CR includes the disappearance of the original monoclonal protein (M-protein) from blood and urine, and <5% plasma cells in the bone marrow, and no increase in size/number of lytic bone lesions, and disappearance of soft tissue plasmacytomas for >=4 weeks. VGPR includes serum and urine M-protein detectable by immunofixation but not electrophoresis, and reduction in 24-hr urinary light chain excretion by <100 mg, and disappearance of soft tissue plasmacytomas for >= 4 weeks, and no increase in size/number of lytic bone lesions. PR includes a >=50% reduction in serum M-protein, and reduction in 24-hr urinary light chain excretion by either >=90% or to <200 mg, and >=50% reduction in size of soft tissue plasmacytomas, and no increase in size/number of lytic bone lesions. MR includes a >=25% and <=49% reduction in serum M-protein. SD does not meet criteria for the other response categories. See outcome #4 for a definition of PD.
Time Frame
up to 7.5 months (eight 28-day cycles)
Title
Kaplan-Meier Estimate for Time to Progression (TTP)
Description
Time to progression was defined as the time from initiation of therapy to progressive disease (PD). PD requires at least one of the following:
>25% increase in serum monoclonal paraprotein (which must also be an absolute increase of at least 5 g/L),
>25% increase in 24-hour urinary light chain excretion (which must also be an absolute increase of at least 200 mg/24 h),
>25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy (which must also be an absolute increase of at least 10%),
definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas,
the development of new bone lesions or soft tissue plasmacytomas,
the development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).
Time Frame
up to 8.6 months
Title
Kaplan-Meier Estimate for Progression-Free Survival
Description
Progression free survival is the time between the date of initiation of therapy to progressive disease (PD) or death from any cause, whichever occurs first. See outcome #4 for a definition of PD.
Time Frame
up to 23 months
Title
Time to the First Response
Description
Time to first response is defined as the time from the initiation of therapy to the first evidence of a confirmed response (ie, CR, VGPR, PR, or MR).
Time Frame
up to 8.5 months
Title
Kaplan-Meier Estimate for Duration of Response
Description
Duration of response (DR) is defined as the time from the first response to progressive disease (PD). See outcome #4 for a PD definition.
Time Frame
up to 8.5 months
Title
Kaplan-Meier Estimate for Overall Survival (OS)
Description
Overall survival is defined as the time from initiation of therapy to death from any cause or last follow-up visit.
Time Frame
up to 23 months
Title
Summary of Participants With Adverse Events (AEs)
Description
Counts of participants who had AEs are summarized in a variety of categories. Severity and relatedness to study drug are in the opinion of the investigator according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0. Severity is rated on a 5-point scale: 1=mild, 2=moderate, 3=severe, 4=life threatening or disabling, and 5= death related to AE. Relatedness is assessed on a 5-point scale: not related, unlikely, possible, probable and definite. Definite, probable and possible answers are reported as 'related' to study medication. Deaths are reported up to 18 months. All the deaths occurred beyond the treatment-emergent timeframe since they occurred 6.5-16 months after the final dosing. All other parts of the summary represent the treatment-emergent timeframe (up to 8.5 months) which is the treatment period plus 30 days.
Time Frame
up to 8.5 months. Deaths are reported up to 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The patient:
has a diagnosis of multiple myeloma.
currently has multiple myeloma with measurable disease.
must have received at least 1 previous treatment regimen and shows signs of progressive disease at the time of study entry.
if a woman of child bearing potential (not surgically sterile or at least 12 months naturally postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study.
if a man, must agree to use an acceptable method of contraception throughout the study and for 90 days after last dose study drug.
must have an Eastern Cooperative Oncology Group (ECOG) performance status not greater than 2.
must have a life-expectancy of greater than 3 months.
must meet specific protocol-related hematological and laboratory criteria within 14 days of enrollment.
Exclusion Criteria:
The patient has:
had a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix).
plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes (POEMS) syndrome.
plasma cell leukemia.
non-measurable multiple myeloma.
Common Terminology Criteria for Adverse Events (CTCAE) grade 2 (or greater) peripheral neuropathy within 14 days before enrollment.
previously participated in a Cephalon-sponsored clinical study with bendamustine.
impaired cardiac function or clinically significant cardiac diseases.
undergone major surgery within 4 weeks prior to screening or has not recovered from side effects of such therapy.
severe hypercalcemia.
other concurrent severe and/or uncontrolled medical or psychiatric conditions.
known positivity for human immunodeficiency virus (HIV) or hepatitis B or C.
a history of allergic reaction attributable to compounds of similar chemical or biological composition to bendamustine, bortezomib, boron, or mannitol.
received chemotherapy within 3 weeks before enrollment, with the exception of nitrosoureas, which should be discontinued at least 6 weeks before enrollment.
received corticosteroids (greater than 10 mg/day prednisone or equivalent) within 3 weeks before enrollment.
received immunotherapy, antibody, or radiation therapy within 4 weeks before enrollment.
a status as a pregnant or lactating woman. Any women becoming pregnant during the study will be withdrawn from the study.
a status as a male whose sexual partner is a woman of childbearing potential not using effective birth control.
used an investigational drug within 1 month before the screening visit.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sponsor's Medical Expert
Organizational Affiliation
Cephalon
Official's Role
Study Director
Facility Information:
Facility Name
Pacific Oncololgy & Hematology
City
Encinitas
State/Province
California
Country
United States
Facility Name
Capitol Hematology Oncology
City
Roseville
State/Province
California
Country
United States
Facility Name
University Of California, San Diego
City
San Diego
State/Province
California
Country
United States
Facility Name
James R. Berenson, M.D., Inc.
City
West Hollywood
State/Province
California
Country
United States
Facility Name
George Washington University
City
Washington
State/Province
District of Columbia
Country
United States
Facility Name
Northshore University Health System
City
Evanston
State/Province
Illinois
Country
United States
Facility Name
Alivin & Lois Lapidus Cancer Institute
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
Center for Cancer and Blood Disorders
City
Bethesda
State/Province
Maryland
Country
United States
Facility Name
Sophia Gordon Cancer Center at Lahey Clinic
City
Burlington
State/Province
Massachusetts
Country
United States
Facility Name
Geisinger Medical Center
City
Danville
State/Province
Pennsylvania
Country
United States
Facility Name
Charleston Hematology Oncology, PA
City
Charleston
State/Province
South Carolina
Country
United States
Facility Name
Family Cancer Center, PLLC
City
Collierville
State/Province
Tennessee
Country
United States
Facility Name
Fairfax Northern Virginia Hematology Oncology
City
Fairfax
State/Province
Virginia
Country
United States
12. IPD Sharing Statement
Citations:
Citation
Berenson JR, Yellin O, Bessudo A, et al. Bendamustine combined with bortezomib has efficacy in patients with relapsed or refractory multiple myeloma: a phase 1/2 study. Blood (ASH Annual Meeting Abstracts). 2011;118 (suppl 21):abstract 1857
Results Reference
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Study of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma
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