Sunitinib in Treating Patients With Relapsed Multiple Myeloma

PRIMARY OBJECTIVES:

I. To assess the number of responses in patients with relapsed multiple myeloma treated with sunitinib (sunitinib malate).

SECONDARY OBJECTIVES:

I. To assess the toxicity of sunitinib malate in patients with relapsed multiple myeloma.

II. To assess time to progression after initial response to sunitinib malate.

OUTLINE:

Patients receive oral sunitinib malate once daily on days 1-42. Treatment repeats every 42 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3-6 months for up to 3 years.

Inclusion criteria

• Diagnosis of relapsed multiple myeloma
• Measurable disease as defined by at least one of the following:

• Serum monoclonal protein ≥ 1.0 g by protein electrophoresis
• Urine monoclonal protein > 200 mg by 24-hour electrophoresis
• Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Monoclonal bone marrow plasmacytosis ≥ 30%
• Not a candidate for stem cell transplantation OR have undergone prior stem cell collection
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy ≥ 3 months
• Absolute neutrophil count ≥ 1,000/microliter (mcL)
• Platelets ≥ 75,000/mcL
• Hemoglobin ≥ 8 g/dL
• Total serum bilirubin normal
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal
• Creatinine < 2.5 mg/dL
• Negative pregnancy test for women of childbearing potential
• No more than 4 prior therapies

• Stem cell transplantation and preceding induction therapy will be considered 1 therapy
• Prior anthracycline exposure or central thoracic radiotherapy that included the heart in the radiotherapy port allowed provided patient has a New York Heart Association (NYHA) class II or better cardiac function on baseline ECHO or multiple gated acquisition scan (MUGA)
• Concurrent bisphosphonates allowed
• At least 7 days since prior and no concurrent cytochrome P450 3A4 (CYP3A4) inhibitors
• At least 12 days since prior and no concurrent CYP3A4 inducers

Exclusion criteria

• Pregnant or nursing women
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
• History of serious ventricular arrhythmia or corrected QT interval (QTc) prolongation
• Poorly controlled hypertension
• Any condition that impairs the ability to swallow and retain sunitinib malate tablets
• Patients with a preexisting thyroid abnormality who are unable to maintain thyroid function in the normal range with medication
• Other active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix or breast
• Concurrent uncontrolled illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements
• Patients who have not recovered from adverse events of prior therapy
• Chemotherapy or radiotherapy ≤ 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study entry
• Any major surgery ≤ 4 weeks prior to study entry
• Nonmyelosuppressive agents ≤ 2 weeks prior to study entry
• Any other prior antiangiogenic agents
• Concurrent high-dose corticosteroids

• Concurrent chronic steroids (up to 20 mg/day prednisone equivalent) allowed for disorders other than amyloid; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• Concurrent therapeutic doses of coumarin-derivative anticoagulants
• Concurrent agents with proarrhythmic potential
• Concurrent combination antiretroviral therapy for HIV-positive patients
• Any other concurrent investigational agents or anticancer therapy