Sunitinib in Treating Patients With Relapsed Multiple Myeloma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00514137
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Arm: 1
• Duration (Months): 35
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Refractory Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma	Drug: sunitinib malate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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

2. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Sunitinib (SU11248) in Multiple Myeloma
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (kinase inhibitor therapy) 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; Oral 37.5 mg each day of the 6-week cycle (continuous dosing).; Other Names: SU11248 sunitinib Sutent

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Cancer Research Consortium	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Shaji Kumar, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00514137
• Other Study ID Numbers: NCI-2009-00208; MC058F; CDR0000560703; N01CM62205
• First Posted: Aug 9, 2007
• Last Update Posted: May 28, 2014
• Last Verified: Mar 1, 2013

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Sunitinib

Study Results

Participant Flow

Recruitment Details	Thirteen participants were accrued from September 2007 to December 2008.
Pre-assignment Detail	All 13 participants were analyzed.

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	13
COMPLETED	13
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	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.
Overall Participants	13
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	9 69.2%
Male	4 30.8%
Region of Enrollment (participants) [Number]
United States	11 84.6%
Hong Kong	1 7.7%
Singapore	1 7.7%

Outcome Measures

1. Primary Outcome

Title	The Number of Confirmed Responses (Complete Response [CR], Very Good Partial Response [VGPR], or Partial Response [PR])
Description	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

Outcome Measure Data

Analysis Population Description

All 13 participants were evaluable for a response

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	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.
Measure Participants	13
Number [participants]	0 0%

2. Secondary Outcome

Title	Event-free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	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.
Measure Participants	13
Median (95% Confidence Interval) [months]	2.86

3. Secondary Outcome

Title	Duration of Response
Description	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

Outcome Measure Data

Analysis Population Description

No analysis was done because there were no confirmed responses.

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	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.
Measure Participants	0

4. Secondary Outcome

Title	Toxicity
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	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.
Measure Participants	13
Grade 3+ Adverse Events	10 76.9%
Grade 4+ Adverse Events	3 23.1%
Grade 5 Adverse Events	0 0%

Adverse Events

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	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.
All Cause Mortality
	Treatment (Kinase Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Kinase Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	5/13 (38.5%)
Blood and lymphatic system disorders
Hemoglobin decreased	2/13 (15.4%)	2
Cardiac disorders
Left ventricular dysfunction	1/13 (7.7%)	1
Gastrointestinal disorders
Vomiting	1/13 (7.7%)	1
General disorders
Pain	1/13 (7.7%)	1
Infections and infestations
Pneumonia	1/13 (7.7%)	1
Investigations
Creatinine increased	1/13 (7.7%)	1
Leukocyte count decreased	1/13 (7.7%)	1
Neutrophil count decreased	2/13 (15.4%)	2
Platelet count decreased	1/13 (7.7%)	1
Renal and urinary disorders
Protein urine positive	1/13 (7.7%)	1
Renal failure	1/13 (7.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/13 (7.7%)	1
Hypoxia	1/13 (7.7%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Kinase Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	13/13 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	8/13 (61.5%)	9
Endocrine disorders
Hypothyroidism	1/13 (7.7%)	1
Gastrointestinal disorders
Constipation	1/13 (7.7%)	1
Diarrhea	6/13 (46.2%)	8
Dyspepsia	4/13 (30.8%)	6
Ear, nose and throat examination abnormal	5/13 (38.5%)	6
Gastritis	1/13 (7.7%)	1
Nausea	5/13 (38.5%)	5
Oral pain	1/13 (7.7%)	1
Vomiting	2/13 (15.4%)	2
General disorders
Edema limbs	1/13 (7.7%)	1
Fatigue	11/13 (84.6%)	19
Fever	2/13 (15.4%)	2
Investigations
Amylase increased	2/13 (15.4%)	3
Leukocyte count decreased	9/13 (69.2%)	11
Lipase increased	2/13 (15.4%)	2
Neutrophil count decreased	7/13 (53.8%)	10
Platelet count decreased	10/13 (76.9%)	14
Weight loss	1/13 (7.7%)	1
Metabolism and nutrition disorders
Anorexia	7/13 (53.8%)	8
Serum calcium decreased	2/13 (15.4%)	4
Musculoskeletal and connective tissue disorders
Bone pain	1/13 (7.7%)	1
Nervous system disorders
Dizziness	1/13 (7.7%)	1
Taste alteration	5/13 (38.5%)	7
Respiratory, thoracic and mediastinal disorders
Dyspnea	6/13 (46.2%)	6
Hemorrhage nasal	2/13 (15.4%)	2
Skin and subcutaneous tissue disorders
Hand-and-foot syndrome	1/13 (7.7%)	1
Rash desquamating	3/13 (23.1%)	5
Skin hypopigmentation	1/13 (7.7%)	3
Vascular disorders
Hypertension	4/13 (30.8%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.