- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00916058
Conditioning Regimen of Bendamustine and Melphalan Followed by Transplant in Patients With Multiple Myeloma
A Phase 1-2 Study of a Novel Conditioning Regimen of Bendamustine and Melphalan Followed by Autologous Stem Cell Transplant for Patients With Multiple Myeloma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Bendamustine (TREANDA™) has been used in clinical trials to treat multiple myeloma. The results from these trials suggest that it may be beneficial in the treatment of multiple myeloma in a different treatment context. Researchers aim to determine if there may be an improved benefit in the context of bone marrow transplant. This initial clinical trial is intended to help determine how safe it is to use bendamustine as a conditioning regimen for bone marrow transplant, and to look for any initial evidence of benefit.
Bendamustine (TREANDA™) is approved by the Food and Drug Administration (FDA) for the treatment of Chronic Lymphocytic Leukemia and Melphalan is a type of chemotherapy drug.
The use of Melphalan alone as a conditioning regimen for Autologous Stem Cell Transplant is considered "Standard of Care," that is, the treatment or process that your doctor would normally follow to treat your disease. Although Bendamustine (TREANDA™) has been used in multiple myeloma research studies, the combination of Bendamustine (TREANDA™) and Melphalan as treatment for Multiple Myeloma is not approved by the FDA, thus the combination therapy used in this research study is considered "investigational."
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10021
- Weill Cornell Medical College
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with multiple myeloma who have received induction therapy and have had stem cells mobilized in preparation for autologous transplantation will be eligible for this study. Patients are also eligible with relapsed or refractory disease, after attempts at more standard approaches, and with the availability of stem cells.
- Patients must be age 18 or older.
- Patients must have a life expectancy of at least 12 weeks.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Patients must provide written informed consent.
Exclusion Criteria:
- Impaired renal function with a measured or calculated creatinine clearance of less than 25 ml/min.
- Impaired hepatic function defined as a bilirubin greater than 1.5 x upper limit of normal (ULN) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5 x ULN.
- Serious active or uncontrolled infection or medical condition.
- Women who are pregnant or breast feeding. Women of childbearing age must use adequate contraception and have a negative pregnancy test.
- Impaired pulmonary function with a diffusing capacity of the lung for carbon monoxide (DLCO) less than 45% predicted.
- Impaired cardiac function with an ejection fraction less than 40% of predicted.
- Other systemic anticancer therapy or ongoing toxicities from such therapy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dose Level 1
Dose Level 1; Bendamustine 30 mg/m^2 total, Melphalan 200 mg/m^2 total (140 mg/m^2 total for patients with Creatinine Clearance <70 ml/min)
|
30 mg/m^2 given on day 2 of melphalan
Other Names:
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
|
Experimental: Dose Level 2
Dose Level 2; Bendamustine 60 mg/m^2 total, Melphalan 200 mg/m^2 total (140 mg/m^2 total for patients with Creatinine Clearance <70 ml/min)
|
30 mg/m^2 given on day 2 of melphalan
Other Names:
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
|
Experimental: Dose Level 3
Dose Level 3; Bendamustine 90 mg/m^2 total, Melphalan 200 mg/m^2 total (140 mg/m^2 total for patients with Creatinine Clearance <70 ml/min)
|
30 mg/m^2 given on day 2 of melphalan
Other Names:
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
|
Experimental: Dose Level 4
Dose Level 4; Bendamustine 120 mg/m^2 total, Melphalan 200 mg/m^2 total (140 mg/m^2 total for patients with Creatinine Clearance <70 ml/min)
|
30 mg/m^2 given on day 2 of melphalan
Other Names:
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
|
Experimental: Dose Level 5
Dose Level 5; Bendamustine 150 mg/m^2 total, Melphalan 200 mg/m^2 total (140 mg/m^2 total for patients with Creatinine Clearance <70 ml/min)
|
30 mg/m^2 given on day 2 of melphalan
Other Names:
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
|
Experimental: Dose Level 6
Dose Level 6; Bendamustine 225 mg/m^2 total, Melphalan 200 mg/m^2 total (140 mg/m^2 total for patients with Creatinine Clearance <70 ml/min)
|
30 mg/m^2 given on day 2 of melphalan
Other Names:
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
|
Experimental: Phase 2
Bendamustine 225 mg/m^2 total, Melphalan 200 mg/m^2 total (140 mg/m^2 total for patients with Creatinine Clearance <70 ml/min)
|
30 mg/m^2 given on day 2 of melphalan
Other Names:
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (Phase 1)
Time Frame: 35 days post-transplant
|
The Maximum Tolerated Dose was not met in Phase 1 of the study.
Phase 2 participants were enrolled at the highest dose administered in Phase 1 (Dose Level 6) and this Outcome Measure is the reported number of dose-limiting toxicities experienced by Phase 1 participants.
DLTs were defined as any grade 3 non-hematologic adverse even that did not resolve within 72 hours, any occurrence of a grade 4 non-hematologic adverse event, or failure to engraft with an absolute neutrophil count of 500/mm^3 and platelet count of 20,000/mm^3 untransfused by Day 35 post-transplant.
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35 days post-transplant
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Overall Response Rate (Phase 2) - Number of Participants Achieving at Least a Partial Response or Better in Disease Status at Day 100 Post-transplant
Time Frame: 100 days post-transplant
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Number of patients achieving at least a partial response or better in disease status at Day 100 post-transplant, as defined by the International Myeloma Working Group (IMWG) disease response criteria.
Partial response in disease status is defined by the IMWG as ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 hours; If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria; If serum and urine M-protein are unmeasurable, and serum-free light assay is also unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma-cell percentage was ≥30%.
In addition to these criteria, if present at baseline, a ≥50% reduction in the size (SPD) of soft tissue plasmacytomas is also required
|
100 days post-transplant
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-Free Survival (Phase 1)
Time Frame: From Day 0 to first incidence of disease progression, up to 1,128 days
|
Time elapsed between Day 0 and disease progression, as defined by the International Myeloma Working Group (IMWG) disease response criteria. Disease progression is defined as an increase of >25% from lowest response value in any one or more of the following:
|
From Day 0 to first incidence of disease progression, up to 1,128 days
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Progression-Free Survival (Phase 2)
Time Frame: From Day 0 to first incidence of disease progression, up to 86 months
|
Time elapsed between Day 0 and disease progression, as defined by the International Myeloma Working Group (IMWG) disease response criteria. Disease progression is defined as an increase of >25% from lowest response value in any one or more of the following:
|
From Day 0 to first incidence of disease progression, up to 86 months
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Overall Survival at 2 Years (Phase 1)
Time Frame: From Day 0 until time of death, assessed up to 2 years.
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Time elapsed between Day 0 and death from any cause, whichever came first, assessed up to 2 years.
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From Day 0 until time of death, assessed up to 2 years.
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Overall Survival at 3 Years (Phase 2)
Time Frame: From Day 0 until time of death, assessed up to 3 years.
|
Time elapsed between Day 0 and death from any cause, whichever came first, assessed up to 3 years.
|
From Day 0 until time of death, assessed up to 3 years.
|
Collaborators and Investigators
Investigators
- Principal Investigator: Tsiporah Shore, M.D., Weill Medical College of Cornell University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
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
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Bendamustine Hydrochloride
- Melphalan
Other Study ID Numbers
- 0812010147
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
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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
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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
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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
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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
-
Prof. Dr. Wolfgang HiddemannHoffmann-La Roche; Mundipharma Research GmbH & Co KGCompleted
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CephalonCompletedMultiple MyelomaUnited States
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Czech Lymphoma Study GroupNot yet recruitingLymphoma, Mantle-CellCzechia
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Novartis PharmaceuticalsTerminatedLymphoma, FollicularUnited States, Belgium, Italy, Hong Kong, Austria, Germany, Japan, Russian Federation, United Kingdom, Canada, Slovakia, Poland, Ukraine, Puerto Rico, Greece, France, Argentina