Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin for Multiple Myeloma
Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin for Multiple Myeloma
This is an open label phase I/II trial to determine the safety and the biologic activity of
 the bendamustine, bortezomib and pegylated liposomal doxorubicin combination.
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.