Sunitinib in Treating Patients With Relapsed Multiple Myeloma

Study Overview
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Brief Summary
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This phase II trial is studying how well sunitinib works in treating patients with relapsed multiple myeloma. Sunitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer

Detailed Description
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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.

Official Title
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A Phase II Trial of Sunitinib (SU11248) in Multiple Myeloma

Conditions
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Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

Intervention / Treatment
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* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (kinase inhibitor therapy)<br>Patients receive 37.5 mg 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. | Drug: sunitinib malate<br>* Oral 37.5 mg each day of the 6-week cycle (continuous dosing).<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Confirmed Responses (Complete Response [CR], Very Good Partial Response [VGPR], or Partial Response [PR]) | A confirmed response is defined as a patient who has achieved response and maintained it on two consecutive evaluations at least 2 weeks apart. A Complete Response (CR) is defined as the complete disappearance of an M-protein and fewer than 5% bone marrow plasmacytosis. A Hematologic Very good partial response (VGPR) is defined as having a ≥ 90% reduction of M-protein from serum, a Urine M-spike to be ≤ 100 mg/24 hours, and a disappearance of soft tissue plasmacytomas. A Partial Response (PR) is defined as having a 50-89% reduction in the level of the serum monoclonal protein, a reduction in 24-hour urinary light chain excretion either by ≥90% or to <200 mg, and a ≥ 50% reduction in size of soft tissue plasmacytoma. | Every 6 weeks from the first initiation of therapy up to 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free Survival | The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. | Time from registration to progression or death due to any cause, assessed up to 3 years | 
| Duration of Response | The distribution of duration of response will be estimated using the method of Kaplan-Meier. | From the documentation of response until the date of progression | 
| Toxicity | Assessed per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Included are the toxicities at least possibly related to the study drug. | From the time of first treatment to up to 30 days after the last day of study drug treatment |