Refractory Multiple Myeloma, Stage III Multiple Myeloma, Stage II Multiple Myeloma, Stage I Multiple Myeloma
Conditions
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.
Interventions
DRUGsunitinib malate
Oral 37.5 mg each day of the 6-week cycle (continuous dosing).
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
Thirteen participants were accrued from September 2007 to December 2008.
Pre-assignment details
All 13 participants were analyzed.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Kinase Inhibitor Therapy) 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. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Treatment (Kinase Inhibitor Therapy) |
|---|---|
| Age, Continuous | 61 years |
| Region of Enrollment Hong Kong | 1 participants |
| Region of Enrollment Singapore | 1 participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 5 / 13 |
Outcome results
Primary
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.
Time frame: Every 6 weeks from the first initiation of therapy up to 72 weeks
Population: All 13 participants were evaluable for a response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Kinase Inhibitor Therapy) | The Number of Confirmed Responses (Complete Response [CR], Very Good Partial Response [VGPR], or Partial Response [PR]) | 0 participants |
Secondary
Duration of Response
The distribution of duration of response will be estimated using the method of Kaplan-Meier.
Time frame: From the documentation of response until the date of progression
Population: No analysis was done because there were no confirmed responses.
Secondary
Event-free Survival
The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
Time frame: Time from registration to progression or death due to any cause, assessed up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Kinase Inhibitor Therapy) | Event-free Survival | 2.86 months |
Secondary
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.
Time frame: From the time of first treatment to up to 30 days after the last day of study drug treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Kinase Inhibitor Therapy) | Toxicity | Grade 3+ Adverse Events | 10 participants |
| Treatment (Kinase Inhibitor Therapy) | Toxicity | Grade 4+ Adverse Events | 3 participants |
| Treatment (Kinase Inhibitor Therapy) | Toxicity | Grade 5 Adverse Events | 0 participants |