Bortezomib, Liposomal Doxorubicin Hydrochloride, Dexamethasone, and Cyclophosphamide in Treating Patients With Multiple Myeloma That Relapsed After Autologous Stem Cell Transplant

Study Overview
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Brief Summary
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This phase II trial is studying how well giving bortezomib together with liposomal doxorubicin hydrochloride, dexamethasone, and cyclophosphamide works in treating patients with multiple myeloma that relapsed after autologous stem cell transplant. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as liposomal doxorubicin hydrochloride, dexamethasone, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with liposomal doxorubicin hydrochloride, dexamethasone, and cyclophosphamide may kill more cancer cells.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the 1-year survival of patients with relapsed multiple myeloma treated with bortezomib, liposomal doxorubicin, dexamethasone, and cyclophosphamide. SECONDARY OBJECTIVES: I. To evaluate response rates in patients treated with this regimen. II. To evaluate the median time to progression in patients treated with this regimen. III. To evaluate the toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Peripheral blood and bone marrow samples may be collected for future research. Patients complete the Functional Assessment of Cancer Therapy (FACT) neurotoxicity questionnaire periodically. After completion of study treatment, patients are followed up every 3 months for 3 years.

Official Title
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A Phase II Study of Bortezomib, Liposomal Doxorubicin, Dexamethasone, and Cyclophosphamide in Patients With Multiple Myeloma Relapsing Within 12 Months of Autologous Stem Cell Transplant

Conditions
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Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: liposomal doxorubicin
* Drug: bortezomib
* Drug: dexamethasone
* Drug: cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of multiple myeloma that was symptomatic at the time of initial diagnosis Must have met the following criteria at one point during the disease course: Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy-proven plasmacytoma Symptomatic disease at initial diagnosis that prompted the initiation of therapy as well as evidence of end-organ damage at the time of diagnosis, including at least 1 of the following: Anemia Hypercalcemia Bone disease (lytic bone lesions or pathologic fracture) Renal dysfunction Disease relapsed < 12 months after autologous stem cell transplantation (SCT) Measurable disease, as defined by the presence of ≥ 1 of the following: Serum M-spike ≥ 1 g/dL Urine M-spike ≥ 200 mg/24 hours Involved free light chain (FLC) ≥ 10 mg/dL (provided the serum FLC is abnormal) Plasma cells ≥ 30% ECOG performance status 0-2 Negative pregnancy test Fertile patients must use effective contraception At least 14 days since prior palliative and/or localized radiotherapy Left ventricular ejection fraction (LVEF) normal by Echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan Hemoglobin > 8 g/dL Platelet count ≥ 75,000/mm^3 (without transfusion support) Absolute neutrophil count (ANC) ≥ 1,000/mm^3 (without use of growth factors) Creatinine < 2.5 mg/dL Direct bilirubin ≤ 1.5 mg/dL Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal All tests below must be performed within 14 days prior to registration: Serum free light chain assay Kappa free light chain Lambda free light chain Prior malignancy allowed provided it was treated curatively and has not relapsed in 5 years Patients with basal cell skin cancer, in situ cervical cancer, or prostate cancer not requiring therapy are eligible Exclusion Criteria: Therapy for relapsed disease following SCT Known allergy to bortezomib or anthracyclines Prior allogeneic SCT Peripheral neuropathy ≥ grade 2 according to the Cancer Therapy Evaluation Program (CTEP) active version of the NCI Common Terminology Criteria for Adverse Events (CTCAE) Concurrent uncontrolled illness that would limit study compliance, including the following: Uncontrolled hypertension Symptomatic congestive heart failure Unstable angina Uncontrolled cardiac arrhythmia Uncontrolled psychiatric illness or social situation Active uncontrolled infection Prior doxorubicin hydrochloride exposure > 240 mg/m^2 Active, uncontrolled seizure disorder Seizures within the past 6 months Pregnant or nursing

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: Treatment (combination chemotherapy)<br>Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. | Drug: liposomal doxorubicin<br>* Given IV<br>* Other names: Doxorubicin Hydrochloride Liposome;Drug: bortezomib<br>* Given subcutaneously.<br>* Other names: LDP-341;Drug: dexamethasone<br>* Given orally<br>* Other names: DXM;Drug: cyclophosphamide<br>* Given IV<br>* Other names: Neosar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One-year Survival in Patients Treated With This Regimen. | Proportion of patients who are still alive at 1 year after registration. | Assessed at 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bortezomib, Liposomal Doxorubicin, Dexamethasone, Cyclophosphamide, refractory multiple myeloma