Study of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma
This study has been completed.
Sponsor:
Cephalon
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier:
NCT00920855
First received: June 11, 2009
Last updated: September 20, 2012
Last verified: September 2012
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Purpose
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).
| Condition | Intervention | Phase |
|---|---|---|
|
Multiple Myeloma |
Drug: bendamustine Drug: bortezomib |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | An Open-Label Study of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma |
Resource links provided by NLM:
Further study details as provided by Teva Pharmaceutical Industries:
Primary Outcome Measures:
- Participants With Dose Limiting Toxicity (DLT) [ Time Frame: Day 1 - 28 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Up to 7.5 months (eight 28-day cycles) ] [ Designated as safety issue: No ]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 [ Time Frame: up to 7.5 months (eight 28-day cycles) ] [ Designated as safety issue: No ]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 Frame: up to 8.6 months ] [ Designated as safety issue: No ]
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 [ Time Frame: up to 23 months ] [ Designated as safety issue: No ]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 Frame: up to 8.5 months ] [ Designated as safety issue: No ]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 [ Time Frame: up to 8.5 months ] [ Designated as safety issue: No ]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) [ Time Frame: up to 23 months ] [ Designated as safety issue: No ]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) [ Time Frame: up to 8.5 months. Deaths are reported up to 18 months ] [ Designated as safety issue: No ]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.
| Enrollment: | 40 |
| Study Start Date: | June 2009 |
| Study Completion Date: | December 2011 |
| Primary Completion Date: | July 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Bendamustine and Bortezomib
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.
|
Drug: bendamustine
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. Other Names:
Drug: bortezomib
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.
Other Name: VELCADE®
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00920855
Locations
| United States, California | |
| Pacific Oncololgy & Hematology | |
| Encinitas, California, United States | |
| Capitol Hematology Oncology | |
| Roseville, California, United States | |
| University Of California, San Diego | |
| San Diego, California, United States | |
| James R. Berenson, M.D., Inc. | |
| West Hollywood, California, United States | |
| United States, District of Columbia | |
| George Washington University | |
| Washington, District of Columbia, United States | |
| United States, Illinois | |
| Northshore University Health System | |
| Evanston, Illinois, United States | |
| United States, Maryland | |
| Alivin & Lois Lapidus Cancer Institute | |
| Baltimore, Maryland, United States | |
| Center for Cancer and Blood Disorders | |
| Bethesda, Maryland, United States | |
| United States, Massachusetts | |
| Sophia Gordon Cancer Center at Lahey Clinic | |
| Burlington, Massachusetts, United States | |
| United States, Pennsylvania | |
| Geisinger Medical Center | |
| Danville, Pennsylvania, United States | |
| United States, South Carolina | |
| Charleston Hematology Oncology, PA | |
| Charleston, South Carolina, United States | |
| United States, Tennessee | |
| Family Cancer Center, PLLC | |
| Collierville, Tennessee, United States | |
| United States, Virginia | |
| Fairfax Northern Virginia Hematology Oncology | |
| Fairfax, Virginia, United States | |
Sponsors and Collaborators
Cephalon
Investigators
| Study Director: | Sponsor's Medical Expert | Cephalon |
More Information
No publications provided
| Responsible Party: | Teva Pharmaceutical Industries ( Cephalon ) |
| ClinicalTrials.gov Identifier: | NCT00920855 History of Changes |
| Other Study ID Numbers: | C18083/1063/MM/US |
| Study First Received: | June 11, 2009 |
| Results First Received: | August 15, 2012 |
| Last Updated: | September 20, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders |
Immune System Diseases Bendamustine Bortezomib Nitrogen Mustard Compounds Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Protease Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on June 13, 2013