Multiple Myeloma Clinical Trial
Official title:
An Open-Label Study of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma
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).
Status | Completed |
Enrollment | 40 |
Est. completion date | December 2011 |
Est. primary completion date | July 2011 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
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. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Alivin & Lois Lapidus Cancer Institute | Baltimore | Maryland |
United States | Center for Cancer and Blood Disorders | Bethesda | Maryland |
United States | Sophia Gordon Cancer Center at Lahey Clinic | Burlington | Massachusetts |
United States | Charleston Hematology Oncology, PA | Charleston | South Carolina |
United States | Family Cancer Center, PLLC | Collierville | Tennessee |
United States | Geisinger Medical Center | Danville | Pennsylvania |
United States | Pacific Oncololgy & Hematology | Encinitas | California |
United States | Northshore University Health System | Evanston | Illinois |
United States | Fairfax Northern Virginia Hematology Oncology | Fairfax | Virginia |
United States | Capitol Hematology Oncology | Roseville | California |
United States | University Of California, San Diego | San Diego | California |
United States | George Washington University | Washington | District of Columbia |
United States | James R. Berenson, M.D., Inc. | West Hollywood | California |
Lead Sponsor | Collaborator |
---|---|
Cephalon |
United States,
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
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. |
Day 1 - 28 | Yes |
Secondary | 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. | Up to 7.5 months (eight 28-day cycles) | No |
Secondary | 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. | up to 7.5 months (eight 28-day cycles) | No |
Secondary | 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). |
up to 8.6 months | No |
Secondary | 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. | up to 23 months | No |
Secondary | 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). | up to 8.5 months | No |
Secondary | 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. | up to 8.5 months | No |
Secondary | 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. | up to 23 months | No |
Secondary | 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. | up to 8.5 months. Deaths are reported up to 18 months | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05027594 -
Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT02412878 -
Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma
|
Phase 3 | |
Completed |
NCT01947140 -
Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
|
Phase 1/Phase 2 | |
Recruiting |
NCT05971056 -
Providing Cancer Care Closer to Home for Patients With Multiple Myeloma
|
N/A | |
Recruiting |
NCT05243797 -
Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation
|
Phase 3 | |
Active, not recruiting |
NCT04555551 -
MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma
|
Phase 1 | |
Recruiting |
NCT05618041 -
The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies
|
N/A | |
Active, not recruiting |
NCT03844048 -
An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
|
Phase 3 | |
Recruiting |
NCT03412877 -
Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer
|
Phase 2 | |
Completed |
NCT02916979 -
Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG
|
Phase 1 | |
Recruiting |
NCT03570983 -
A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion
|
Phase 2 | |
Terminated |
NCT03399448 -
NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells)
|
Phase 1 | |
Completed |
NCT03665155 -
First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody
|
Phase 1/Phase 2 | |
Completed |
NCT02812706 -
Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT05024045 -
Study of Oral LOXO-338 in Patients With Advanced Blood Cancers
|
Phase 1 | |
Active, not recruiting |
NCT03792763 -
Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients
|
Phase 2 | |
Active, not recruiting |
NCT03989414 -
A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM)
|
Phase 1/Phase 2 | |
Withdrawn |
NCT03608501 -
A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation
|
Phase 2 | |
Recruiting |
NCT04537442 -
Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT02546167 -
CART-BCMA Cells for Multiple Myeloma
|
Phase 1 |