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

Sherif Farag, MB, BS

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Multiple Myeloma

Treatments

Drug: Bendamustine

Drug: Doxorubicin

Drug: Bortezomib

Drug: Filgrastim

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01177683

MM08-141

Details and patient eligibility

About

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.

Full description

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)

Enrollment

32 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.