Phase II Study of Velcade, Decadron, and Doxil Followed by Cyclophosphamide in Multiple Myeloma

PRIMARY STUDY OBJECTIVES

* To evaluate the efficacy of the combination of bortezomib, dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide as a therapy for two different subsets of multiple myeloma patients:

  1. Patients post first line therapy
  2. Patients with relapsed/refractory disease who are bortezomib-naïve
* To evaluate the safety of the combination of bortezomib and dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide as therapy for patients with multiple myeloma.

SECONDARY STUDY OBJECTIVES

* To evaluate the role of the combination of bortezomib dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide on the ability to collect \> 10 x 106 CD34+ cells/kg in \< 7 collections (for both subsets of multiple myeloma patients).
* To evaluate the survival of patients who receive the combination of bortezomib dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide (for both subsets of patients).


Eligibility Criteria:
Inclusion Criteria:

* Subject must voluntarily sign and understand written informed consent.
* Confirmed diagnosis of multiple myeloma as specified by the SWOG criteria and is detailed in Appendix I.
* Measurable disease as defined the following:

  1. For patients post induction therapy, any measurable paraprotein in the serum or urine and/or any plasmacytoma present on physical exam or imaging.
  2. For patients with relapsed/refractory disease, \> 0.5 g/dL serum monoclonal protein, \> 0.1 g/dL serum free light chains, \> 0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s).
* Age \> or = than 18 years at the time of signing the informed consent form.
* Karnofsky performance status\> or =70% (\>60% if due to bony involvement of myeloma).
* Group A (post-induction therapy)- patients who have received only one prior treatment regimen (eg VAD, Thal/Dex, BLT-D, MP, BiRD, or DVd) with at least 20 patients having received a Revlimid based regimen or Group B(\>1st line of therapy)- patients with relapsed/refractory multiple myeloma who have received two or more prior treatment regimens .
* If the patient is a woman of childbearing age, she must have a negative serum or urine pregnancy test within 7 days of starting study and must use effective contraception throughout the course of the study.
* Life expectancy \> 12 weeks.
* Absolute neutrophil count (ANC)\> or = 1500 cells/mm3 (\> or = 1000 for patients with bone marrow biopsy displaying \> 50% involvement by myeloma)
* Platelets count \> or = 50,000/mm3 (\> or = 30,000 for patients with bone marrow biopsy displaying \> 50% involvement by myeloma)
* Hemoglobin \> 9.0 g/dL
* Serum SGOT/AST \<3.0 x upper limits of normal (ULN)
* Serum SGPT/ALT \<3.0 x upper limits of normal (ULN)
* Serum creatinine \< 2.5 mg/dL or creatinine clearance \> 40ml/min
* Serum total bilirubin \< 1.5 x ULN
* Patients must have a MUGA scan with LVEF \>50%

Exclusion Criteria:

* Patients with non-secretory MM (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine) unless measurable disease is available with imaging techniques such as MRI and PET scan.
* Prior treatment with bortezomib.
* Peripheral neuropathy of \> Grade 2 as defined by CTCAE Version 3.0 (see Appendix II)
* History of allergic reactions to compounds containing mannitol, bortezomib, conventional formulation of doxorubicin HCL or the components of DOXIL.
* Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ³ 5 years.
* NYHA Class III or IV heart disease. History of active unstable angina, congestive heart disease, serious uncontrolled cardiac arrhythmia or myocardial infarction within 6 months.
* Female patients who are pregnant or breastfeeding. Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
* Known HIV or hepatitis A, B, or C positivity
* Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
* Any concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk, including, but not limited to, uncontrolled hypertension, uncontrolled diabetes, active uncontrolled infection, and/or acute chronic liver disease (i.e., hepatitis, cirrhosis).
* No prior anti-myeloma therapy within 2 weeks of treatment initiation.