Sunitinib in Treating Patients With Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00451048
• Collaborator: (none)
• Enrollment: 10
• Locations: 4
• Arm: 1
• Duration (Months): 68
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial is studying how well sunitinib works in treating patients with myelodysplastic syndromes or chronic myelomonocytic leukemia. Sunitinib may stop the growth of abnormal cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic Syndromes; Secondary Myelodysplastic Syndromes	Drug: sunitinib malate	Phase 2

Detailed Description

OBJECTIVES:

1. Determine the overall response rate (complete response, partial response, or hematological improvement) in patients with intermediate-2 or high-risk myelodysplastic syndromes or chronic myelomonocytic leukemia treated with sunitinib malate.

2. Determine the duration of response in patients treated with this drug. III. Determine the overall survival of patients treated with this drug. IV. Determine the progression-free survival of patients treated with this drug. V. Determine the time to disease progression in patients treated with this drug.

3. Determine the toxicity of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 3-4 weeks and then monthly thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Sunitinib Malate (Sutent®; SU11248) in Patients With Intermediate-2 or High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients will receive sunitinib malate (SU11248) by mouth once a day. Treatment may continue for as long as benefit is shown.	Drug: sunitinib malate; Given orally; Other Names: SU11248 sunitinib Sutent

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (Complete Response, Partial Response, or Hematologic Improvement) Defined by the International Working Group Criteria [Up to 6 years]

Secondary Outcome Measures

1. Number Participants With Complete, Partial or Hematologic Improvement Response [Up to 6 years]

   Assessed by achievement of Complete Response (CR), Partial Response (PR) or Hematologic Improvement (HI)

2. Overall Survival [At 6 months and 1 year]

3. Progression-free Survival [At 6 months and 1 year]

4. Time to Progression [At 6 months and 1 year]

5. Highest Severity of Observed Adverse Events Assessed by Common Terminology Criteria or Adverse Events Version 3.0 (CTCAE v3.0) [Up to 6 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• MDS syndromes meeting 1 of the following: Intermediate-2 disease, high-risk disease (IPSS score>=1.5)

• CMML: WBC>12,000/mm^{3, Intermediate-2 disease with WBC=<12,000/mm}3, high-risk disease (IPSS score>=1.5) with WBC=<12,000/mm^3

• Patients with insufficient/inadequate metaphases for cytogenetic analysis are eligible if bone marrow blasts are >10% and/or 2-3 cytopenias are present

• No known brain metastases

• Life expectancy>12 weeks

• ECOG PS 0-2/Karnofsky PS 60-100%

• Calcium=<3.0 mmol/L

• Bilirubin normal

• AST and ALT=<2.5 times upper limit of normal

• Creatinine normal/creatinine clearance>=60 mL/min

Exclusion Criteria:

• No history of significant ECG abnormalities including but not limited to: ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation>=3 beats in a row); QTc prolongation (i.e.QTc interval>=500msec)

• No history of allergic reaction to compounds of similar chemical/biological composition to sunitinib malate

• No NYHA class III-IV congestive heart failure

• Patients with history of NYHA class II congestive heart failure who are asymptomatic on treatment are eligible

• No abdominal fistula/G perforation/intraabdominal abscess within past 28 days

• No serious cardiovascular disease within past 12 months including: cerebrovascular accident or transient ischemic attack, myocardial infarction, cardiac arrhythmia, stable or unstable angina, symptomatic congestive heart failure, coronary or peripheral artery bypass graft or stenting

• No pulmonary embolism within past 12 months

• No uncontrolled hypertension (systolic BP>=140 mmHg/diastolic BP>=90 mmHg)

• No condition impairing ability to swallow/retain sunitinib malate tablets including: GI tract disease resulting in inability to take oral medication, requirement for IV alimentation, prior surgical procedures affecting absorption, active peptic ulcer disease

• No serious/nonhealing wound, ulcer, or bone fracture

• No uncontrolled pre-existing thyroid abnormality

• No concurrent uncontrolled illness including ongoing/active infection

• No psychiatric illness/social situation that would preclude study participation

• Not pregnant/nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception

• 4 weeks since prior major surgery

• Prior central thoracic radiotherapy that included heart in radiotherapy port allowed provided NYHA congestive heart failure=<class II

• Prior anthracycline exposure allowed provided NYHA congestive heart failure=<class II

• No other prior therapy for MDS/CMML except epoetin alfa, darbepoetin alfa, filgrastim or sargramostim

• At least 2 weeks since prior epoetin alfa

• At least 4 weeks since prior darbepoetin alfa

• No other prior antiangiogenic agents including but not limited to: bevacizumab, sorafenib tosylate, pazopanib hydrochloride, AZD2171, vatalanib, VEGF Trap

• More than 7 days since prior and no concurrent potent CYP3A4 inhibitors

• More than 12 days since prior and no concurrent potent CYP3A4 inducers including: Rifampin, Rifabutin, Carbamazepine, Phenobarbital, Phenytoin, Hypericum perforatum, Efavirenz, Tipranavir

• No concurrent birth control patch/oral birth control pills/depot/injectable birth control methods

• No concurrent therapeutic coumarin-derivative anticoagulants

• Low dose(=<2mg) warfarin for prophylaxis of thrombosis allowed

• Low molecular weight heparin allowed if INR=<1.5

• No concurrent agents with proarrhythmic potential including: Terfenadine, Quinidine, Procainamide, Disopyramide, Sotalol, Probucol, Bepridil, Haloperidol, Risperidone, Indapamide, Flecainide acetate

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
2	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
3	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
4	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Karen Yee, University Health Network-Princess Margaret Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00451048
• Other Study ID Numbers: NCI-2009-00211; PHL-063; CDR0000535656; N01CM62203
• First Posted: Mar 22, 2007
• Last Update Posted: Sep 4, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Leukemia; Preleukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Syndrome; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Arm I
Arm/Group Description	Patients will receive sunitinib by mouth once a day. Treatment may continue for as long as benefit is shown. sunitinib malate: Given orally
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Arm I
Arm/Group Description	Patients will receive sunitinib by mouth once a day. Treatment may continue for as long as benefit is shown. sunitinib malate: Given orally
Overall Participants	10
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 20%
>=65 years	8 80%
Sex: Female, Male (Count of Participants)
Female	3 30%
Male	7 70%
Region of Enrollment (participants) [Number]
United States	1 10%
Canada	9 90%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (Complete Response, Partial Response, or Hematologic Improvement) Defined by the International Working Group Criteria
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients will receive sunitinib by mouth once a day. Treatment may continue for as long as benefit is shown. sunitinib malate: Given orally
Measure Participants	10
Number [percentage of participants]	10 100%

2. Secondary Outcome

Title	Number Participants With Complete, Partial or Hematologic Improvement Response
Description	Assessed by achievement of Complete Response (CR), Partial Response (PR) or Hematologic Improvement (HI)
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

No patient achieved CR, PR or HI as response.

Arm/Group Title	Arm I
Arm/Group Description	Patients will receive sunitinib by mouth once a day. Treatment may continue for as long as benefit is shown. sunitinib malate: Given orally
Measure Participants	10
Number [participants]	0 0%

3. Secondary Outcome

Title	Overall Survival
Time Frame	At 6 months and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients will receive sunitinib by mouth once a day. Treatment may continue for as long as benefit is shown. sunitinib malate: Given orally
Measure Participants	5
Median (95% Confidence Interval) [months]	13.9

4. Secondary Outcome

Title	Progression-free Survival
Time Frame	At 6 months and 1 year

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Arm I
Arm/Group Description	Patients will receive sunitinib by mouth once a day. Treatment may continue for as long as benefit is shown. sunitinib malate: Given orally
Measure Participants	0

5. Secondary Outcome

Title	Time to Progression
Time Frame	At 6 months and 1 year

Outcome Measure Data

Analysis Population Description

Date were not collected

Arm/Group Title	Arm I
Arm/Group Description	Patients will receive sunitinib by mouth once a day. Treatment may continue for as long as benefit is shown. sunitinib malate: Given orally
Measure Participants	0

6. Secondary Outcome

Title	Highest Severity of Observed Adverse Events Assessed by Common Terminology Criteria or Adverse Events Version 3.0 (CTCAE v3.0)
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients will receive sunitinib by mouth once a day. Treatment may continue for as long as benefit is shown. sunitinib malate: Given orally
Measure Participants	10
Number [highest grade of adverse event reported]	4

Adverse Events

Arm/Group Title	Arm I
Arm/Group Description	Patients will receive sunitinib by mouth once a day. Treatment may continue for as long as benefit is shown. sunitinib malate: Given orally
All Cause Mortality
	Arm I
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	4/10 (40%)
Blood and lymphatic system disorders
Febrile neutropenia	3/10 (30%)
Gastrointestinal disorders
Small intestinal obstruction	1/10 (10%)
Anal pain	1/10 (10%)
Gastrointestinal disorders - Other, specify	1/10 (10%)
General disorders
Fever	1/10 (10%)
Pain	1/10 (10%)
Infections and infestations
Encephalitis infection	1/10 (10%)
Other (Not Including Serious) Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Anemia	10/10 (100%)
General disorders
Fatigue	10/10 (100%)
Investigations
Neutrophil count decreased	9/10 (90%)
Platelet count decreased	9/10 (90%)
Lymphocyte count decreased	8/10 (80%)
White blood cell decreased	8/10 (80%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	9/10 (90%)

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.