Bortezomib, Doxorubicin Hydrochloride Liposome, and Thalidomide as First-line Therapy in Treating Patients With Previously Untreated Stage I, II, or III Multiple Myeloma
Bortezomib, Doxorubicin Hydrochloride Liposome, and Thalidomide as First-line Therapy in Treating Patients With Previously Untreated Stage I, II, or III Multiple Myeloma
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes
 needed for cell growth. Drugs used in chemotherapy, such as doxorubicin hydrochloride
 liposome, work in different ways to stop the growth of cancer cells, either by killing the
 cells or by stopping them from dividing. Thalidomide may stop the growth of multiple myeloma
 by blocking blood flow to the cancer. Giving bortezomib together with doxorubicin
 hydrochloride liposome and thalidomide may kill more cancer cells.

 PURPOSE: This phase II trial is studying how well giving bortezomib together with doxorubicin
 hydrochloride liposome and thalidomide works as first-line therapy in treating patients with
 previously untreated 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