Bortezomib, Doxorubicin Hydrochloride Liposome, and Thalidomide as First-line Therapy in Treating Patients With Previously Untreated Stage I, II, or III Multiple Myeloma
Condition: Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Intervention: bortezomib; pegylated liposomal doxorubicin hydrochloride; thalidomide
Intervention description: IV; IV; Oral
Intervention MeSH terms: Thalidomide; Doxorubicin; Liposomal doxorubicin; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma

Summary:

      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.
    

Eligibility criteria:

        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