Alternative Schedule of Velcade/Dexamethasone Plus Doxil for Patients With Multiple Myeloma

Study Overview
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Brief Summary
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The current study is being conducted to evaluate the possibility that a different schedule of bortezomib, doxorubicin HCl liposome, and dexamethasone might decrease the incidence of peripheral neuropathy yet maintain similar efficacy and allow maintenance of bortezomib dosing for a longer period.

Official Title
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A Phase II, Open Label Study Evaluating an Alternative Schedule of Velcade/Dexamethasone Plus Doxil in the Treatment of Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: bortezomib
* Drug: dexamethasone
* Drug: doxorubicin HCl liposome


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is at least 18 years of age. Patient has confirmed diagnosis of relapsed/refractory multiple myeloma with measurable disease by serum or urine. Measurable disease defined as monoclonal protein of ≥ 1g/dl on serum protein electrophoresis (SPEP) or > 200 mg urine M protein/ 24 hours Patient has received at least 1 prior treatment regimen. (Prior treatment with bortezomib is allowed.) Patient has ECOG ≤ 2 Patient provides voluntary written informed consent before performance of any study-relates procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. Patients who have received prior high dose chemotherapy with stem cell support are eligible for this study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study. Exclusion Criteria: Patient has a platelet count of < 50, 000 cells/mm³, within 14 days before enrollment. Patient has an absolute neutrophil count (ANC) ≤ 750/mm³ within 14 days before enrollment. Patient has a calculated or measured creatinine clearance of < 20 mL/min within 14 days before enrollment and/or serum creatinine ≥ 2.5 mg/dl. Patient has hemoglobin < 7.5 g/dl. Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment. Myocardial infarction within 6 months prior to enrollment or has (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant. Patient has received a total cumulative dosage of anthracyclines exceeding 550 mg/m2. Patient has hypersensitivity to boron or mannitol. Patient has history of hypersensitivity reactions to a conventional formulation of doxorubicin HCl or the components of DOXIL. Patient has clinically significant coexisting illness unrelated to myeloma. Patient has uncontrolled diabetes. Patient has plasma cell leukemia. Patient has serum bilirubin > 1.5 x upper normal limit, alanine aminotransaminase (ALT), aspartate aminotransferase (AST) > 2.5 x upper normal limit (ULN), or alkaline phosphatase > 2.5 x ULN. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (B-hCG)pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Patient has received other investigational drugs within 14 days before enrollment. Patient has serious medical or psychiatric illness likely to interfere with participation in this clinical study.

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

| Intervention/Treatment |
| --- |
|Drug: bortezomib|Patients will be treated with bortezomib at 1.3mg/m^2 on Days 1, 4, 15, and 18 every 28 days (cycle).|
|Drug: dexamethasone|Dexamethasone tablets will be given at 20mg daily on Days 1, 2, 4, 5, 15, 16, 18, and 19 every 28 days (cycle).|
|Drug: doxorubicin HCl liposome|Patients will receive intravenous doxorubicin HCl liposome injection given at 30 mg/m^2 on Day 4 every 28 days (cycle).|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-emergent Peripheral Neuropathy |  | Every 4 weeks from start of treatment until end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (TTP) |  | TTP was measured from day 1 of treatment until time of progression, assessed up to 40 months | 
| Number of Participants With Treatment Response | Complete Response (CR), Partial Response (PR), and Minor Response (MR) each required stable bone disease and normal calcium levels. CR also required 100% serum protein electrophoresis (SPEP) reduction, negative immunofixation (IF), 100% urine protein electrophoresis (UPEP)reduction, and <5% plasma cells in bone marrow. PR also required >=50% SPEP reduction, >=90% UPEP reduction, and >=50% reduction in plasma cells in bone marrow. MR also required >=25% SPEP reduction, >=50% UPEP reduction, and > 25% reduction in plasma cells. | Every 8 weeks from start of treatment until end of treatment | 
| Relative Dose Intensity of Bortezomib | Relative dose intensity is defined as actual dose/scheduled dose. Bortezomib is administered on Days 1, 4, 15, and 18 every 28 days. | Each dose of bortezomib (days 1, 4, 15, and 18 every 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed Multiple Myeloma, Refractory Multiple Myeloma