Sunitinib in Treating Patients With Relapsed Multiple Myeloma

Phase 2

Completed

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

Interventions: Drug: sunitinib malate

Registration Number: NCT00514137

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (kinase inhibitor therapy)	sunitinib malate	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.

Primary Outcome Measures

Name	Time	Method
The Number of Confirmed Responses (Complete Response [CR], Very Good Partial Response [VGPR], or Partial Response [PR])	Every 6 weeks from the first initiation of therapy up to 72 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Response	From the documentation of response until the date of progression	The distribution of duration of response will be estimated using the method of Kaplan-Meier.
Event-free Survival	Time from registration to progression or death due to any cause, assessed up to 3 years	The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
Toxicity	From the time of first treatment to up to 30 days after the last day of study drug treatment	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.