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

A Phase I/II Trial of Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin in Patients With Relapsed or Refractory Multiple Myeloma: Hoosier Cancer Research Network MM08-141

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.