OBJECTIVES:
Primary
- To determine the maximum tolerated dose and recommended phase II dose of obatoclax mesylate when given in combination with bortezomib in patients with relapsed or refractory multiple myeloma. (Phase I)
- To evaluate the response rate (complete response, partial response, and very good partial response) in patients treated with this regimen. (Phase II)
Secondary
- To determine the duration of progression-free and overall survival of these patients.
- To evaluate the incidence of toxicities of this regimen in these patients.
OUTLINE: This is a multicenter, phase I, dose-escalation study of obatoclax mesylate followed by a phase II study.
Patients receive obatoclax mesylate IV over 3 hours and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years.
DISEASE CHARACTERISTICS:
- 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 disease as 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 NOTE: If both serum and urine m-components are present, both must be followed in order to evaluate response
- 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
PATIENT CHARACTERISTICS:
- 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
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- 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
Last updated: 03/26/2012
NCT ID: NCT00719901
IRB Number:07-008520
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