Bortezomib, Doxorubicin Hydrochloride Liposome, and Dexamethasone Followed by Thalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Multiple Myeloma
Condition: Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Intervention: bortezomib; dexamethasone; pegylated liposomal doxorubicin hydrochloride; thalidomide
Intervention MeSH terms: Thalidomide; Dexamethasone; Doxorubicin; Liposomal doxorubicin; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
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; refractory 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 and dexamethasone, work in different ways to stop the growth of cancer cells, either
      by killing the cells or stopping them from dividing. Thalidomide may stop the growth of
      cancer cells by blocking blood flow to the cancer. Giving bortezomib together with
      doxorubicin hydrochloride liposome and dexamethasone followed by thalidomide, dexamethasone,
      and bortezomib may kill more cancer cells.

      PURPOSE: This phase II trial is studying the side effects and how well giving bortezomib
      together with doxorubicin hydrochloride liposome and dexamethasone followed by thalidomide
      and dexamethasone with or without bortezomib works in treating patients with multiple
      myeloma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically and serologically confirmed multiple myeloma meeting one of the
             following criteria:

               -  High-risk myeloma, defined as symptomatic International Staging System (ISS)
                  stage 2 or 3 multiple myeloma

               -  Soft-tissue involvement with myeloma in the form of a soft-tissue plasmacytoma

               -  Extension of a plasmacytoma into soft tissues

               -  Primary resistant myeloma, defined as unchanged or progressive myeloma despite
                  two courses of standard treatment

          -  No ISS stage 1 multiple myeloma without soft-tissue involvement

          -  No smoldering myeloma

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-3

          -  Life expectancy > 16 weeks

          -  Absolute granulocyte count ≥ 1,500/mm³ (unless low granulocyte counts are due to
             multiple myeloma)

          -  Platelet count ≥ 100,000/mm³ (unless low platelet counts are due to multiple myeloma)

          -  Bilirubin ≤ 2.0 mg/dL

          -  AST and ALT < 3 times upper limit of normal (ULN)

          -  Alkaline phosphatase < 3 times ULN

          -  LVEF ≥ 50% by MUGA or ECHO

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective barrier contraception 4 months prior to, during,
             and for 4 weeks after completion of study treatment

          -  No active thromboembolic disease on anticoagulation

          -  No active angina or myocardial infarction within the past 6 months

          -  No pre-existing neuropathy or sensory or neuropathic pain ≥ grade 2

          -  No concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in
             situ of the cervix

               -  Prior malignancies that have not required antitumor treatment within the past 24
                  months allowed

               -  Patients with a history of stage I or II (T1a/b) prostate cancer (detected
                  incidentally at transurethral resection of prostate [TURP] and comprising < 5% of
                  resected tissue) allowed if the prostate-specific antigen has remained normal
                  since TURP

          -  No known HIV positivity or AIDS-related illness

          -  No other medical condition or reason that, in the opinion of the investigator, would
             preclude study compliance

          -  No history of hypersensitivity reactions attributed to a conventional formulation of
             doxorubicin hydrochloride or to components of pegylated doxorubicin hydrochloride
             liposome, bortezomib, boron, or mannitol

        PRIOR CONCURRENT THERAPY:

          -  Prior radiotherapy allowed

          -  No more than 2 courses of prior initial chemotherapy for multiple myeloma

          -  No prior bortezomib

          -  No prior high-dose steroids (not including taper) for more than 1 month in duration
             for emergent indications, such as hypercalcemia or life-threatening lesions (e.g.,
             spinal cord compromise) (in high-risk patients)