RATIONALE: Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving pegylated liposomal doxorubicin hydrochloride together with bortezomib, cyclophosphamide, and dexamethasone may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects of giving pegylated liposomal doxorubicin hydrochloride together with bortezomib, cyclophosphamide, and dexamethasone and to see how well it works in treating patients with multiple myeloma
PRIMARY OBJECTIVES: I. To determine efficacy of this novel combination in newly diagnosed patients with multiple myeloma. SECONDARY OBJECTIVES: I. To determine the toxicity of this novel combination regimen in previously treated patients and newly diagnosed patients with multiple myeloma. OUTLINE: Patients receive cyclophosphamide intravenously (IV) or orally (PO) over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of treatment, patients are followed up every 3 months for 2 years, then annually up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
31
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Maximum Tolerated Dose of This Combination of Drugs as Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Cohort 1) [MTD Cyclophosphamide, MTD Bortezmib, MTD Docxorubicin]
If 3 patients of cohort 1 require dose reduction of one or more of the medications for toxicity attributed to the drug or drugs, then the starting dose level will be reduced for that drug or drugs for future patients. The initial dosing of drugs for cohort 2 will be permitted to be one dose level above the maximal tolerated doses of cohort 1. Note that this Outcome Measure shows MTD for cyclophosphamide, bortezomib and doxorubicin. MTD for dexamethasone is include in a separate table due to the different Unit of Measure.
Time frame: Up to 90 days after initiation of study treatment
Disease Response Rate (Cohort II)
Disease response using Blade Multiple Myeloma Response Criteria in newly diagnosed (Cohort II) patients who completed at least one cycle of treatment. There were 24 evaluable patients in Cohort II.
Time frame: up to 28 days after last cycle of treatment
Maximum Tolerated Dose of This Combination of Drugs as Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Cohort 1). [Dexamethasone MTD]
If 3 patients of cohort 1 require dose reduction of one or more of the medications for toxicity attributed to the drug or drugs, then the starting dose level will be reduced for that drug or drugs for future patients. The initial dosing of drugs for cohort 2 will be permitted to be one dose level above the maximal tolerated doses of cohort 1. Note that this Outcome Measure will only describe the MTD for dexamethasone. Dexamethasone could not be reported with the MTD for the other three drugs due to a different Unit of Measure.
Time frame: Up to 90 days after initiation of study treatment
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