- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01177683
Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin for Multiple Myeloma
A Phase I/II Trial of Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin in Patients With Relapsed or Refractory Multiple Myeloma: Hoosier Cancer Research Network MM08-141
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Phase I component Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11 Doxorubicin 30 mg/m2 IV over 1 hour, Day 4 Bendamustine escalating cohorts IV over 1 hour, Days 1 and 4 1 Cycle = 28 days
Phase II component Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11 Doxorubicin 30 mg/m2 IV over 1 hour, Day 4 Bendamustine at MTD IV over 1 hour, Days 1 and 4 Filgrastim (if defined in MTD) 5 µg/kg/day SC, Starting day 6 until neutrophil recovery to ANC >1000
1 Cycle = 28 days; Patients will continue treatment for a total of up to 8 cycles.
ECOG Performance Status: 0-2
Hematopoietic:
- Absolute neutrophil count (ANC) ≥ 1.2 x K/mm3
- Platelets ≥ 75 x K/mm3
Hepatic:
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- AST ≤ 2.5 x ULN
- ALT ≤ 2.5 x ULN
Renal:
- Serum creatinine < 3.0 mg/dL
Cardiovascular:
- LVEF >45% corrected by MUGA scan or echocardiogram.
- No unstable angina pectoris or recent myocardial infarction (within 6 months)
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Indiana University Melvin and Bren Simon Cancer Center
-
Indianapolis, Indiana, United States, 46219
- IU Health Central Indiana Cancer Centers
-
Indianapolis, Indiana, United States, 46256
- Community Regional Cancer Center
-
Lafayette, Indiana, United States, 47904
- IU Health Arnett Cancer Center
-
-
Michigan
-
Wyoming, Michigan, United States, 49519
- Metro Health Cancer Care
-
-
New York
-
Rochester, New York, United States, 14642
- University of Rochester Medical Center
-
-
Ohio
-
Cleveland, Ohio, United States, 44106
- University Hospitals Seidman Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- A histologically established diagnosis of multiple myeloma with evidence of relapse or refractory disease.
- Must have a detectable serum or urine M-Protein by protein electrophoresis that is at least 500 mg/dL (serum) or 1 gm/24 hours (urine), respectively, or serum free light chain level >100 mg/l for the involved free light chain.
- Must have received at least one (1) prior line of systemic treatment that has included either lenalidomide or thalidomide.
- Must be willing to provide correlative blood samples.
Exclusion Criteria:
- Must not have received an excessive cumulative dose of anthracycline
- No ≥ grade 2 peripheral neuropathy.
- No cytotoxic chemotherapy within 30 days prior to registration for protocol therapy.
- No autologous stem cell transplant within 6 months prior to registration for protocol therapy
- No prior radiation therapy to > 25% of bone marrow forming bones (i.e., pelvis) within 30 days prior to registration for protocol therapy. See Study Procedures Manual to calculate percent of prior radiation.
- No current corticosteroid therapy in doses greater than 10 mg daily of prednisone (or equivalent) if given for management of co-morbid conditions.
- No known central nervous system involvement by myeloma.
- No poorly controlled intercurrent illness including, but not limited to, ongoing or active infection, poorly controlled diabetes, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social climate that in the opinion of the investigator would limit compliance with study requirements.
- No patients known to be positive for HIV, or active Hepatitis A, B, or C.
- No major surgery within 30 days prior to registration for protocol therapy. Placement of a venous access device within 30 days prior to registration for protocol therapy is allowed.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm 1
Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.
|
Phase I component: Bendamustine escalating cohorts to determine MTD, IV over 1 hour, Days 1 and 4 Phase I and II components: Pegylated liposomal doxorubicin, 30 mg/m2 IV over 1 hour, Day 4 Phase I and II components: Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11 Phase II component: Bendamustine at at MTD IV over 1 hour, Days 1 and 4 Phase II component: Filgrastim (if defined in MTD) 5 µg/kg/day SC, starting day 6 until neutrophil recovery to ANC >1000 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: MTD of Bendamustine When Combined With Bortezomib and Pegylated Liposomal Doxorubicin.
Time Frame: From C1D1 up to a maximum of 7 months or until death
|
In the first phase, MTD of bendamustine was determined in combination with bortezomib and pegylated liposomal doxorubicin to gain a better idea of safe dosing before proceeding with the second phase to assess efficacy.
Assuming myelosuppression being a dose-limiting effect that could have been overcome with growth factor support, MTD of the combination with myeloid growth factor support was also tested.
|
From C1D1 up to a maximum of 7 months or until death
|
Phase II : Overall Response Rate
Time Frame: From C1D1 up to a maximum of 52 months or until death
|
Overall response rate (CR+PR) of bendamustine in association with bortezomib and pegylated liposomal doxorubicin was assessed in patients with relapsed or refractory Multiple Myeloma.
Per modified International Myeloma Working Group criteria: Complete Response (CR) : Negative for monoclonal protein by immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow ; PR : 50% or more reduction in serum M-protein and 90% or more reduction in urine M-protein or to <200 mg/24hours or a 50% or more reduction in free light chain level ; Overall Response (OR) = CR +PR.
|
From C1D1 up to a maximum of 52 months or until death
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I & Phase II : Toxicity of Treatment Regimen
Time Frame: From C1D1 until death or up to a maximum of 54 months
|
Toxicity profile (for all patients) were presented by rate of overall toxicity and rates of grade 3 or 4 toxicities analyzed separately and combined.
|
From C1D1 until death or up to a maximum of 54 months
|
Phase II : Time to Progression
Time Frame: From C1D1 up to a maximum of 54 months or until death
|
The time from the start of treatment (i.e., first dose) of MM patients treated with bendamustine, bortezomib and pegylated liposomal doxorubicin to disease progression, with disease progression and death due to disease progression as events and deaths due to causes other than progression as censored. Censoring date will be the last disease evaluation date for patient without progression/death or date of death due to other diseases for patients' deaths due to other causes.Per modified International Myeloma Working Group criteria: Progressive disease (PD) is reported if any one of the following criteria is met: Increase of 25% or more in serum or urine M-protein from baseline;Serum M-protein and/or the absolute increase must be ≥0.5 g/dL;Urine M-protein and/or absolute increase must be ≥200 mg/24 hours ; Development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas;Development of hyperc. |
From C1D1 up to a maximum of 54 months or until death
|
Phase II: Progression-free Survival (PFS)
Time Frame: From C1D1 up to a maximum of 54 months until death
|
The time from the start of treatment of MM patients treated with bendamustine, bortezomib and pegylated liposomal doxorubicin. to disease progression or death (regardless of cause of death), whichever comes first. Censoring date will be the last disease evaluation date.Per modified International Myeloma Working Group criteria: Progressive disease (PD) is reported if any one of the following criteria is met: Increase of 25% or more in serum or urine M-protein from baseline;Serum M-protein and/or the absolute increase must be ≥0.5 g/dL;Urine M-protein and/or absolute increase must be ≥200 mg/24 hours ; Development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas;Development of hyperc. |
From C1D1 up to a maximum of 54 months until death
|
Phase II: Duration of Survival
Time Frame: From C1D1 up to a maximum of 52 months
|
Duration of MM patients treated with bendamustine, bortezomib and pegylated liposomal doxorubicin.
from first date of at least partial response to the time of progression or death due to disease progression as events, with disease progression and death due to disease progression as events and deaths due to causes other than progression as censored.
Censoring date will be the last disease evaluation date or date of death due to other causes as appropriate.
|
From C1D1 up to a maximum of 52 months
|
Phase II: Overall Survival
Time Frame: From C1D1 up to a maximum of 54 months or until death
|
The time from the start of treatment to death from any cause with last date known alive as censoring date.
|
From C1D1 up to a maximum of 54 months or until death
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Sherif Farag, M.B., B.S., Hoosier Cancer Research Network
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Bendamustine Hydrochloride
- Bortezomib
- Doxorubicin
Other Study ID Numbers
- MM08-141
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Myeloma
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
-
National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
Clinical Trials on Bendamustine
-
University of ArizonaCephalonCompletedOvarian CancerUnited States
-
Aptevo TherapeuticsCompletedChronic Lymphocytic Leukemia (CLL)United States, Austria, Germany, Poland, Spain
-
NYU Langone HealthCephalonTerminated
-
M.D. Anderson Cancer CenterWithdrawnLymphoma | Leukemia
-
M.D. Anderson Cancer CenterCephalonTerminatedAcute Myeloid Leukemia | Acute Lymphoblastic Leukemia | Chronic Myeloid Leukemia | Myelodysplastic SyndromeUnited States
-
Novartis PharmaceuticalsCompletedChronic Lymphocytic Leukemia (CLL) | Leukaemia, Lymphocytic, ChronicUnited States, Belgium, Italy, Greece, Russian Federation, Spain, Poland, Czech Republic
-
CephalonCompletedMultiple MyelomaUnited States
-
Prof. Dr. Wolfgang HiddemannHoffmann-La Roche; Mundipharma Research GmbH & Co KGCompleted
-
Columbia UniversityCompletedHodgkin Lymphoma | Anaplastic Large Cell LymphomaCanada, United States
-
Georgetown UniversityGlaxoSmithKline; CephalonTerminatedChronic Lymphocytic Leukemia | Small Lymphocytic LymphomaUnited States