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
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
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.
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.
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:
Disease relapsed < 12 months after autologous stem cell transplantation (SCT)
Measurable disease, as defined by the presence of ≥ 1 of the following:
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:
Prior malignancy allowed provided it was treated curatively and has not relapsed in 5 years
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:
Prior doxorubicin hydrochloride exposure > 240 mg/m^2
Active, uncontrolled seizure disorder
Seizures within the past 6 months
Pregnant or nursing
Elkton MD, Maryland 21921, United States