Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin for Multiple Myeloma

Phase I component Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11 Doxorubicin 30 mg/m2 IV
over 1 hour, Day 4 Bendamustine escalating cohorts IV over 1 hour, Days 1 and 4 1 Cycle = 28
days

Phase II component Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11 Doxorubicin 30 mg/m2
IV over 1 hour, Day 4 Bendamustine at MTD IV over 1 hour, Days 1 and 4 Filgrastim (if defined
in MTD) 5 µg/kg/day SC, Starting day 6 until neutrophil recovery to ANC >1000

1 Cycle = 28 days; Patients will continue treatment for a total of up to 8 cycles.

ECOG Performance Status: 0-2

Hematopoietic:

- Absolute neutrophil count (ANC) ≥ 1.2 x K/mm3

- Platelets ≥ 75 x K/mm3

Hepatic:

- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

- AST ≤ 2.5 x ULN

- ALT ≤ 2.5 x ULN

Renal:

- Serum creatinine < 3.0 mg/dL

Cardiovascular:

- LVEF >45% corrected by MUGA scan or echocardiogram.

- No unstable angina pectoris or recent myocardial infarction (within 6 months)

Inclusion Criteria:

- A histologically established diagnosis of multiple myeloma with evidence of relapse or
refractory disease.

- Must have a detectable serum or urine M-Protein by protein electrophoresis that is at
least 500 mg/dL (serum) or 1 gm/24 hours (urine), respectively, or serum free light
chain level >100 mg/l for the involved free light chain.

- Must have received at least one (1) prior line of systemic treatment that has included
either lenalidomide or thalidomide.

- Must be willing to provide correlative blood samples.

Exclusion Criteria:

- Must not have received an excessive cumulative dose of anthracycline

- No ≥ grade 2 peripheral neuropathy.

- No cytotoxic chemotherapy within 30 days prior to registration for protocol therapy.

- No autologous stem cell transplant within 6 months prior to registration for protocol
therapy

- No prior radiation therapy to > 25% of bone marrow forming bones (i.e., pelvis) within
30 days prior to registration for protocol therapy. See Study Procedures Manual to
calculate percent of prior radiation.

- No current corticosteroid therapy in doses greater than 10 mg daily of prednisone (or
equivalent) if given for management of co-morbid conditions.

- No known central nervous system involvement by myeloma.

- No poorly controlled intercurrent illness including, but not limited to, ongoing or
active infection, poorly controlled diabetes, symptomatic congestive heart failure,
cardiac arrhythmia, or psychiatric illness/social climate that in the opinion of the
investigator would limit compliance with study requirements.

- No patients known to be positive for HIV, or active Hepatitis A, B, or C.

- No major surgery within 30 days prior to registration for protocol therapy. Placement
of a venous access device within 30 days prior to registration for protocol therapy is
allowed.