Bortezomib, Doxorubicin Hydrochloride Liposome, and Thalidomide as First-line Therapy in Treating Patients With Previously Untreated Stage I, II, or III Multiple Myeloma

OBJECTIVES:

Primary

• To determine the overall response rate (complete response and partial response) in patients previously untreated stage I, II, or III multiple myeloma.

Secondary

• To evaluate the complete response rate in patients treated with this regimen.
• To determine the time to disease progression from the start of this therapy in patients treated with this regimen.

OUTLINE: Patients receive low-dose oral thalidomide once a day on days 1-28, bortezomib IV on days 1, 4, 15, and 18, and doxorubicin hydrochloride liposome IV over 60-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with residual disease who continue to show response after completion of 6 courses may receive 2 additional courses for a total of 8 courses.

After completion of study treatment, patients are followed every 3 months.

DISEASE CHARACTERISTICS:

• Diagnosis of stage I, II, or III multiple myeloma requiring therapy
• No prior systemic therapy for multiple myeloma

• Patients who have received steroids or radiotherapy for cord compression or spinal cord disease are eligible for this study
• Patients who have received 1 prior course of antimyeloma therapy may be enrolled at the investigator's discretion provided disease progression is not noted

PATIENT CHARACTERISTICS:

Inclusion criteria

• Karnofsky performance status 60-100%
• Platelet count ≥ 75,000 cells/mm^3 (< 75,000 cells/mm^3 secondary to extensive bone marrow disease allowed at the PI's discretion with appropriate transfusion support)
• ANC ≥ 1,000 cells/mm^3
• Hemoglobin ≥ 8.0 g/dL (< 8 g/dL secondary to extensive bone marrow disease allowed at the PI's discretion with appropriate transfusion support)
• Creatinine clearance > 20 mL/min
• AST and ALT ≤ 2 times upper limit of normal (ULN) OR ≤ 3 times ULN (in the presence of liver metastases)
• Alkaline phosphatase ≤ 2 times ULN OR ≤ 3 times ULN (in the presence of liver metastases)
• Total bilirubin ≤ 2 times ULN OR ≤ 3 times ULN (in the presence of liver metastases)
• Ejection fraction ≥ 50% by MUGA or 2-D echocardiogram
• Negative pregnancy test
• Fertile patients must use at least 1 highly effective and 1 additional effective contraception method 4 weeks prior to, during, and 3 months after completion of study therapy
• HIV-negative
• Must have sufficient mental capacity to understand the explanation of the study and to provide informed consent
• Willingness and ability to comply with the FDA-mandated S.T.E.P.S. program

Exclusion criteria

• Pregnant or lactating
• Active, serious infections uncontrolled by antibiotics
• Any medical condition or reason that, in the investigator's opinion, makes the patient unsuitable to participate in this clinical trial
• History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride or the components of doxorubicin hydrochloride liposome or bortezomib, boron, or mannitol
• Any of the following conditions:

• History of uncontrolled New York Heart Association class II-IV heart disease or clinical evidence of congestive heart failure
• Myocardial infarction within the past 6 months
• Uncontrolled angina
• Severe uncontrolled ventricular arrhythmias, ECG evidence of acute ischemia, or active conduction system abnormalities
• Peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics