Bendamustine, Wkly Bortezomib, Lenalidomide and Dexamethasone for Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of the study is to determine the safety and efficacy of the use of bendamustine in combination with a commonly used combination chemotherapy to treat relapsed and refractory multiple myeloma. The study will be conducted in two phases. Participants in phase I will receive 1 of 4 escalating doses of bendamustine. Once the maximum tolerated dose of bendamustine is determined, phase II of this trial will begin. Participants in phase II will receive the maximum tolerated dose of bendamustine in combination with standard of care chemotherapy.

Detailed Description
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Multiple myeloma is a multi-organ neoplastic disorder caused by the clonal proliferation of plasma cells. It has an incidence of about 4.5/100,000 per year in the U.S., making it the second most common hematologic malignancy. For many years, alkylating agents have been the backbone of treatment. The combination of melphalan and prednisone was, for many years, the standard of care for patients who were not candidates for autologous transplantation. Melphalan continues to be the primary conditioning agent for autologous transplant,and cyclophosphamide has also gained a foothold in the treatment of this disease. The introduction of novel agents has fundamentally changed the landscape of treating this disease, although the true effects on survival are not yet known. Immunomodulatory agents and proteosome inhibitors, including thalidomide, lenalidomide and bortezomib have been used in both newly diagnosed and relapsed patients. Currently, there is intense clinical research on the optimal way to combine these novel agents with the traditional backbones of treatment - including alkylators, with one another and, eventually, with the subsequent iterations of these classes of drugs. However, despite the therapeutic excitement surrounding this disease, most patients will relapse and a cure remains an elusive goal.

Official Title
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An Open-Label Phase I/II Study of Bendamustine, Weekly Bortezomib, Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Bendamustine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with relapsed and/or refractory myeloma who have received between 1-4 prior lines of therapy Must have adequate liver and renal function Zubrod Performance Status (ZPS) of 2 or better Must have measurable disease Exclusion Criteria: Peripheral neuropathy of grade II or higher Thrombocytopenia (platelets less than 50,000/uL) Neutropenia (ANC<1000/uL) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.4 X ULN Total bilirubin >1.5 X upper limit of normal (ULN) Creatinine clearance of less than 45 milliliters per minute (mL/min) Patients with HIV Patients with active hepatitis Pregnant or lactating women Individuals of child-bearing potential not using adequate contraception Individuals unable to provide informed consent

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<br>Bendamustine is combined with standard chemotherapy. | Drug: Bendamustine<br>* The first group of three patients to enter the study will receive a 25 mg/m^2 dose of bendamustine. If this dose is found to be safe, the next three patients will receive 50 mg/m^2. Using a modified Fibonacci dose-escalation design, the dose will continue to increase at a rate of 25 mg/m^2 until the highest safe dose of bendamustine is found. The maximum dose will be 125 mg/m^2. Bendamustine and bortezomib will be given through a catheter twice a week every 21 days. Dexamethasone and lenalidomide will be given orally. In general, a cycle of chemotherapy will last 21 days.<br>* Other names: Treanda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Experiencing a Toxicity | The number of patients experiencing at least one toxicity at the lowest dose of bendamustine. A toxicity is defined as one or more of the following: Upper respiratory infection; anemia; thrombocytopenia; neutropenia; shortness of breath on exertion; decreased appetite; nausea; neuropathy; anxiety; arthritis; and hypercalcemia. | 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treanda, Relapsed Multiple Myeloma, Refractory Multiple Myeloma, Bendamustine, Bortezomib, Lenalidomide, Dexamethasone, Velcade, Revlimid