Obatoclax and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

Inclusion Criteria:

Symptomatic multiple myeloma, meeting the following criteria at original diagnosis:

Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma
Symptomatic disease (e.g.,anemia, hypercalcemia, bone disease, or renal dysfunction) that requires the initiation of therapy

Measurable diseases assessed by one of the following:

Monoclonal plasma cells detectable in the bone marrow
Monoclonal serum spike detectable by serum protein electrophoresis or immunofixation
Monoclonal protein detectable in the urine by electrophoresis or immunofixation
Abnormal levels of the serum free light chains with an abnormal ratio between kappa and lambda
Progressive disease after ≥ 1 prior therapy for myeloma

Previously treated with ≤ 10 courses (30 weeks) of bortezomib and had no disease progression during therapy OR completed bortezomib therapy within the past 6 weeks

No prior discontinuation of bortezomib therapy due to drug intolerance
No known brain metastases

No intracranial edema, intracranial metastasis, or active epidural disease

Patients with lytic lesions of the cranium secondary to myeloma are eligible
ECOG performance status 0-2
Life expectancy > 6 months
ANC ≥ 1,000/mm³
Platelet count ≥ 50,000/mm³
Bilirubin normal
AST and ALT ≤ 2.5 times upper limit of normal (ULN)
Creatinine ≤ 2 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No peripheral neuropathy > NCI toxicity grade 2
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to obatoclax mesylate or bortezomib

No concurrent uncontrolled illness including, but not limited to the following:

Ongoing or active infection
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia, including QTc > 450 msec
Psychiatric illness/social situations that would limit compliance with study requirements
No history of seizure disorder
No other neurological disorder or dysfunction that, in the opinion of the investigator, would confound the evaluation of neurologic and other adverse events associated with obatoclax mesylate
At least 14 days since prior chemotherapy and recovered
More than 28 days since prior experimental drugs and/or investigational agents
No concurrent CYP interactive medications
No concurrent combination antiretroviral therapy for HIV-positive patients

No other concurrent anticancer therapy

Growth factors and bisphosphonates are allowed as medically indicated
Prednisone (≤ 10 mg per day) allowed provided there has been no dose increase within the past 2 weeks
No other concurrent investigational agents