Bendamustine Hydrochloride, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

Study Overview
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Brief Summary
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This phase II trial studies side effects and how well bendamustine hydrochloride, bortezomib, and dexamethasone work in treating patients with newly diagnosed multiple myeloma. Drugs used in chemotherapy, such as bendamustine hydrochloride and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bendamustine hydrochloride with bortezomib and dexamethasone may kill more cancer cells.

Detailed Description
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PRIMARY OBJECTIVES: I. Establish the response rate of induction therapy following 4 cycles of the combination regimen bendamustine (bendamustine hydrochloride), bortezomib and dexamethasone (BBd) in patients with newly diagnosed multiple myeloma. II. Describe the tolerability and toxicities of this regimen. III. Provide one-year progression-free survival and one-year overall survival data following this therapeutic strategy. OUTLINE: Patients receive bendamustine hydrochloride intravenously (IV) over 30 minutes on days 1 and 2; bortezomib subcutaneously (SC) on days 1, 8, 15, and 22; and dexamethasone orally (PO) on days 1, 8, 15, and 22. Treatment repeats every 35 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving less than a very good partial response (VGPR) or with more than 10% bone marrow plasmacytosis may receive 2 additional courses. NOTE: Patients requiring immediate reduction in paraprotein during course 1 only receive bendamustine hydrochloride IV over 30 minutes on days 1 and 2; bortezomib IV on days 1, 4, 8, and 11; and dexamethasone PO on days 1-4. After completion of study treatment, patients are followed up for 1 year.

Official Title
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Phase II Study of Bendamustine, Bortezomib, and Dexamethasone (BBD) for Newly Diagnosed Patients With Multiple Myeloma

Conditions
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Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

Intervention / Treatment
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* Drug: Bendamustine hydrochloride
* Drug: Bortezomib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New diagnosis of multiple myeloma with no prior history of systemic treatment (Exceptions include corticosteroids, bisphosphonates, single agent cyclophosphamide, <= 21 days of the first cycle of a planned regimen >= 18 years of age ECOG <= 3 Signed informed consent Measurable serum paraprotein on SPEP or serum free light chains and ratio, or quantifiable Bence-Jones proteinuria on 24 hour urine specimen. If the monoclonal protein has merged with the beta region we will follow the serum immunoglobulin of the involved heavy chain and comment on either partial remission (PR, as judged by two protocol investigators) or complete remission (CR, as defined by the achievement of PR as above and the resolution of the monoclonal protein by immunofixation in the serum and urine.) Exclusion Criteria: Failure to sign informed consent Smoldering myeloma, monoclonal gammopathy of undetermined significance (MGUS), or plasma cell leukemia History of previously treated smoldering myeloma Grade 3 or above peripheral neuropathy Uncontrolled human immunodeficiency virus (HIV) Active hepatitis A, B or C Pregnant or lactating females Total bilirubin >3 times the upper limit of normal ASLT/ALT > 2.5 times the upper limit of normal

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bendamustine, Bortezomib, Dexamethasone (Standard)<br>Patients receive bendamustine hydrochloride IV over 30 minutes on days 1 and 2; bortezomib SC on days 1, 8, 15, and 22; and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 35 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving less than a VGPR or with more than 10% bone marrow plasmacytosis may receive 2 additional courses. | Drug: Bendamustine hydrochloride<br>* Given IV<br>* Other names: SDX-105;Drug: Bortezomib<br>* Given SC<br>* Other names: Cytomib;Drug: Dexamethasone<br>* Given PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Participants That Experience Overall Response Following 4 Cycles of the Combination Regimen BBd | ORR (partial remission or better) to induction therapy following 4 cycles of the combination regimen BBd. | At least 140 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Grade 3-4 Adverse Events From the Combination of Bendamustine Hydrochloride, Bortezomib, and Dexamethasone Based on the Common Terminology Criteria Version 4.0 | All adverse events are tracked during the course of the trial. Adverse events with a grade of 3-4 will be tracked and recorded. | Up to 1 year | 
| Count of Participants That Experience Very Good Partial Remission (VGPR) | Very good partial remission (VGPR) to induction therapy following 4 cycles of the combination regimen BBd. As defined as no dectable M-protein on SPEP (Serum protein electrophoresis) but positive IFX (Immunofixation) on serum or urine and >90% reduction of M-protein in serum and urine | Up to 1 year | 
| Count of Participants That Experience Progression-free Survival (PFS) | The amount of participants that survive one year after treatment with BBd and do not experience worsening disease. | 1 year | 
| Count of Participants That Experience Overall Survival (OS) | The amount of participants that start treatment with BBd and survive at least one year post treatment completion. | 1 year |