A Phase 1 Dose Escalation Study of Bortezomib (Velcade®), Pegylated Liposomal Doxorubicin (Doxil®), and Vorinostat (Suberoylanilide Hydromaxic Acid, Saha, Zolinzatm) in Patients With Relapse/Refractory Multiple Myeloma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of multiple myeloma

- Relapsed or refractory disease

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy ≥ 3 months

- ANC ≥ 1.0 x 10^9/L (no granulocyte growth factor support, e.g., G-CSF or GM-CSF
allowed)

- Platelet count ≥ 100 x 10^9/L (erythropoietin allowed, no platelet or RBC transfusion
within the past 2 weeks)

- Hemoglobin ≥ 8 g/dL (erythropoietin allowed, no platelet or RBC transfusion within
the past 2 weeks)

- Creatinine clearance ≥ 30 mL/min

- AST or ALT ≤ 2.5 times upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- LVEF ≥ 45% by MUGA or ECHO

- Symptomatic neuropathy < grade 2

- No known history of HIV

- No active or serious infection, medical or psychiatric illness that would preclude
study participation

- No active hepatitis B or C infection

- No other prior or concurrent malignancy except for adequately treated basal cell or
squamous cell carcinoma of the skin, in situ malignancy, low-risk prostate cancer
after curative therapy, or other cancer for which the patient has been disease-free
for ≥ 3 years

- No history of hypersensitivity reaction to bortezomib or any of its components
(boron, mannitol), vorinostat, doxorubicin hydrochloride, or any of the components of
PLD

- No serum potassium ≤ 3.0 or serum magnesium ≤ 1.6 that cannot be corrected with
supplementation are excluded

- Patients must have adequate cardiovascular function, defined by all of the following:

- No EKG evidence of active, clinically significant conduction system
abnormalities

- No EKG evidence of QTc prolongation > grade 2

- NOTE: Any EKG abnormality at screening has to be documented by the investigator as
not medically significant.

PRIOR CONCURRENT THERAPY:

- No limit to number of prior treatment regimens

- At least 30 days since prior therapy and recovered

- At least 3 months since prior autologous stem cell transplantation and recovered

- Prior allogeneic stem cell or bone marrow transplantation allowed provided the
following criteria are met:

- More than 1 year since transplantation

- No longer receiving immunosuppressive therapy or treatment for graft-versus-host
disease (GVHD) prophylaxis

- No active GVHD

- No active, uncontrolled infections

- No major surgery within the past 3 weeks

- No prior anthracycline dose > 360 mg/m^2 for doxorubicin hydrochloride (including
pegylated liposomal doxorubicin hydrochloride [PLD]) or 720 mg/m^2 for epirubicin
hydrochloride

- No prior or concurrent histone deacetylase inhibitor (e.g., valproic acid)

- No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) during course 1

- No other concurrent investigational or anticancer agent