Study of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma
|ClinicalTrials.gov Identifier: NCT00920855|
Recruitment Status : Completed
First Posted : June 15, 2009
Results First Posted : September 17, 2012
Last Update Posted : October 4, 2012
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: bendamustine Drug: bortezomib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label Study of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma|
|Study Start Date :||June 2009|
|Actual Primary Completion Date :||July 2011|
|Actual Study Completion Date :||December 2011|
U.S. FDA Resources
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.
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®
- Participants With Dose Limiting Toxicity (DLT) [ Time Frame: Day 1 - 28 ]
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.
- Percentage of Participants With An Overall Tumor Response As Assessed By the Investigator [ Time Frame: Up to 7.5 months (eight 28-day cycles) ]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) ]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 ]
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 ]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 ]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 ]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 ]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 ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00920855
|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|
|Study Director:||Sponsor's Medical Expert||Cephalon|