Modified Bortezomib-based Combination Therapy for Multiple Myeloma

Study Overview
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Brief Summary
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To investigate the efficacy of a modified bortezomib based combination therapy for patients with multiple myeloma.

Detailed Description
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Multiple myeloma (MM) is a common hematological malignancy in Chinese elderly population. The application of novel drugs improved the clinical outcome and survival of MM patients,even though MM remains an incurable hematological malignancy. Bortezomib is a typical one among these novel agents, its application resulted in great success, but its adverse events and high expense restricted its widely usage. Investigators modified the dose and frequency of bortezomib administration in combination therapy: Patients in the modified group received regimen with bortezomib (1.6mg/㎡) as an intravenous bolus once weekly on day 1, 8 in a 3 weeks cycle, in combination with dexamethasone,with or without doxorubicin/ cyclophosphamide/mitoxsnteone/thalidomide，while patients in the control group received similar combination therapy except with conventional bortezomib (1.3mg/㎡) administration twice weekly on day 1,4, 8,11. The aim of this study is to investigate whether the modified bortezomib-based therapy may attain a similar efficacy as the conventional ones.

Official Title
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An Open-Label Phase IV Study of the Efficacy of Bortezomib-based Combination Therapy the Treatment of Subjects With Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Dexamethasone
* Drug: Doxorubicin
* Drug: Cyclophosphamide
* Drug: Mitoxsnteone
* Drug: Thalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of multiple myeloma based on standard diagnosis criteria: plasmacytomas on tissue biopsy bone marrow plasmacytosis monoclonal immunoglobulin spike on serum electrophoresis lytic bone lesions. Must have relapsed or relapsed/refractory disease 18 years of age or older All baseline studies must be performed within 21 days of enrollment. ECOG performance status of 0 to 2 Exclusion Criteria: Renal insufficiency (serum creatinine levels > 2mg/dL) Concomitant therapy medications that include corticosteroids Peripheral neuropathy of Grade 3 or greater or painful Grade 2 Evidence of mucosal or internal bleeding and/or platelet refractory ANC < 1000 cells/mm3 Hemoglobin < 8.0 g/dL AST (SGOT and ALT) > 2 x ULN Intolerance to bortezomib or CC-5013 in the past or significant allergy to either compound, boron or mannitol Known hypersensitivity to thalidomide or the development of erythema nodosum Active infection or serious co-morbid medical condition Pregnant or breast-feeding women Prior malignancy with the last three years except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, on in-situ prostate cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: modified BZ group<br>Patients with newly diagnosed or pre-treated MM(prior therapy not including bortezomib) received regimen with bortezomib (1.6mg/㎡) as an intravenous bolus once weekly on day 1, 8 in a 3 weeks cycle, in combination with dexamethasone,with or without doxorubicin/ cyclophosphamide/mitoxsnteone/thalidomide | Drug: Bortezomib<br> <br> * Other names: velcade;Drug: Dexamethasone<br> <br> Drug: Doxorubicin<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Mitoxsnteone<br> <br> Drug: Thalidomide<br> <br> |
| Active Comparator: conventional BZ group<br>Patients with newly diagnosed or pre-treated MM(prior therapy not including bortezomib) received bortezomib (1.3mg/㎡) administration twice weekly on day 1,4, 8,11 in a 3 weeks cycle, in combination with dexamethasone,with or without doxorubicin/ cyclophosphamide/mitoxsnteone/thalidomide | Drug: Bortezomib<br> <br> * Other names: velcade;Drug: Dexamethasone<br> <br> Drug: Doxorubicin<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Mitoxsnteone<br> <br> Drug: Thalidomide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease responses to treatment | Response evaluated by changes of serum M-component(g/L) through Serum quantitative immunoglobulins and Serum immunofixation electrophoresis. (g/L) | one year |