Sunitinib in Treating Patients With Relapsed or Refractory Diffuse or Mediastinal Large B-Cell Lymphoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00392496
• Collaborator: (none)
• Enrollment: 19
• Location: 1
• Arm: 1
• Duration (Months): 59
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase II trial is studying how well sunitinib works in treating patients with relapsed or refractory diffuse or mediastinal large B-cell lymphoma. 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
Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma	Drug: sunitinib malate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the response rate in patients with relapsed or refractory, diffuse or mediastinal, large B-cell lymphoma treated with sunitinib malate.

2. Determine the toxicity of this drug in these patients. III. Determine the effects of this drug on peripheral blood biomarkers, circulating endothelial cells, and their precursors in these patients.

OUTLINE: This is a non-randomized, open-label, multicenter study.

Patients receive sunitinib malate orally once daily on days 1-28. Treatment repeats every 4 weeks for a maximum of 12 courses in the absence of disease progression or unacceptable toxicity.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Sunitinib (SU11248; NSC 736511; IND 74019), an Oral Multi-Targeted Tyrosine Kinase Inhibitor, in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I This is a non-randomized, open-label, multicenter study. Patients receive sunitinib malate orally once daily on days 1-28. Treatment repeats every 4 weeks for a maximum of 12 courses in the absence of disease progression or unacceptable toxicity.	Drug: sunitinib malate; Given orally; Other Names: SU11248 sunitinib Sutent

Outcome Measures

Primary Outcome Measures

1. Objective Tumor Response [Up to 3 years]

   It is defined as per the Report of the International workshop to standardize response criteria for non-Hodgkin's lymphoma and reviewed independently

Eligibility Criteria

Criteria

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

Criteria:

• Histologically confirmed diffuse or mediastinal large B-cell lymphoma*, meeting the following criteria: Advanced or metastatic disease, Incurable by standard therapies, Relapsed or refractory disease [Note: *Patients with diffuse large B-cell lymphoma whose disease has transformed from an earlier diagnosis of low grade lymphoma (i.e., an indolent histology) are eligible]

• Bidimensionally measurable disease** by CT scan, MRI, or physical exam, with >= 1 disease site meeting 1 of the following criteria: Lymph nodes >= 1.5 cm x 1.5 cm by spiral CT scan, Non-nodal regions >= 1 cm x 1 cm by MRI, CT scan, or physical exam [Note: **Bone lesions are not considered bidimensionally measurable disease]

• Received 1-2 prior chemotherapy regimens that included doxorubicin hydrochloride; Prior stem cell transplantation and high-dose chemotherapy is considered one regimen; One prior non-chemotherapy regimen in the form of radiation allowed; Measurable disease must be outside the previously irradiated area;

• No sole site of disease in a previously irradiated area unless progressive disease or new lesions are documented; Low-dose palliative radiotherapy may be allowed

• No known brain metastases

• Life expectancy >= 12 weeks

• ECOG performance status 0-1

• Absolute granulocyte count >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

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

• Bilirubin normal

• Calcium =< 3 mmol/L

• Creatinine =< 1.25 times ULN OR creatinine clearance >= 60 mL/min

• LVEF normal by MUGA

• None of the following in the past 12 months: cardiac arrhythmia, cerebrovascular accident (CVA), coronary/peripheral artery bypass graft or stenting, myocardial infarction, stable or unstable angina, symptomatic congestive heart failure, transient ischemic attack, pulmonary embolism

• No uncontrolled hypertension (systolic blood pressure >= 140 mm Hg or diastolic blood pressure >= 90 mm Hg)

• No New York Heart Association (NYHA) class III or IV heart disease

• No QTc prolongation (QTc interval >= 500 msec) or other significant ECG abnormalities

• No other prior malignancies except nonmelanoma skin cancer, in situ cervical cancer, or other solid tumors curatively treated with no evidence of disease for >= 5 years

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

• No other serious illness or medical condition that would preclude study participation, including, but not limited to, the following:

active, uncontrolled infection, serious or nonhealing wound, ulcer, or bone fracture, history of significant neurologic or psychiatric disorder that would impair the ability to obtain consent or limit compliance

• Other medical condition that might be aggravated by treatment

• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days

• No bowel obstruction

• No condition that would impair the ability to swallow and retain sunitinib malate tablets, including any of the following:

Gastrointestinal tract disease resulting in inability to take oral medication or a requirement for IV alimentation, Prior surgical procedures affecting absorption, Active peptic ulcer disease

• No pre-existing hypothyroidism unless euthyroid on medication

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• At least 28 days since prior chemotherapy

• At least 28 days since prior radiotherapy and recovered; radiotherapy must have involved < 30% of functioning bone marrow

• At least 28 days since prior major surgery and recovered

• At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following: rifampin, phenytoin, rifabutin, hypericum perforatum (St. John's wort), carbamazepine, efavirenz, phenobarbital, tipranavir,

• At least 7 days since prior and concurrent CYP3A4 inhibitors, including any of the following: azole antifungals (e.g., ketoconazole, itraconazole), verapamil, clarithromycin, HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, nelfinavir), erythromycin, delavirdine, diltiazem,

• No prior therapy with other antiangiogenic agents or multitargeted tyrosine kinase inhibitors, including any of the following:

bevacizumab, sorafenib tosylate, pazopanib, thalidomide, AZD2171 vandetanib, AMG 706, vatalanib, VEGF Trap

• No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin); Concurrent dosing of =< 2 mg of warfarin daily for prophylaxis of thrombosis is allowed; Concurrent low molecular weight heparin is allowed provided INR is =< 1.5

• No other concurrent anticancer treatments, including investigational agents

• No concurrent agents with proarrhythmic potential, including any of the following: terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, flecainide

• No concurrent combination antiretroviral therapy for HIV-positive patients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cancer Institute of Canada Clinical Trials Group	Kingston	Ontario	Canada	K7L 3N6

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Rena Buckstein, Canadian Cancer Trials Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00392496
• Other Study ID Numbers: NCI-2009-00692; NCI-2009-00692; CDR0000652059; NCIC-182; NCIC-182
• First Posted: Oct 26, 2006
• Last Update Posted: May 15, 2014
• Last Verified: Apr 1, 2013

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Sunitinib

Study Results

Participant Flow

Recruitment Details	This trial was centrally activated on November 8, 2006 and closed to accrual on March 24, 2009. Patients were recruited from 5 cancer centres in Canada

Arm/Group Title	Arm I
Arm/Group Description	This is a non-randomized, open-label, multicenter study. Patients receive sunitinib malate orally once daily on days 1-28. Treatment repeats every 4 weeks for a maximum of 12 courses in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	19
COMPLETED	19
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Arm I
Arm/Group Description	This is a non-randomized, open-label, multicenter study. Patients receive sunitinib malate orally once daily on days 1-28. Treatment repeats every 4 weeks for a maximum of 12 courses in the absence of disease progression or unacceptable toxicity.
Overall Participants	17
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	7 41.2%
Male	10 58.8%
Region of Enrollment (participants) [Number]
Canada	17 100%

Outcome Measures

1. Primary Outcome

Title	Objective Tumor Response
Description	It is defined as per the Report of the International workshop to standardize response criteria for non-Hodgkin's lymphoma and reviewed independently
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

patients evaluable for response

Arm/Group Title	Arm I
Arm/Group Description	This is a non-randomized, open-label, multicenter study. Patients receive sunitinib malate orally once daily on days 1-28. Treatment repeats every 4 weeks for a maximum of 12 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	15
Number [participants]	0 0%

Adverse Events

Arm/Group Title	Arm I
Arm/Group Description	This is a non-randomized, open-label, multicenter study. Patients receive sunitinib malate orally once daily on days 1-28. Treatment repeats every 4 weeks for a maximum of 12 courses in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Arm I
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	13/17 (76.5%)
Cardiac disorders
Grade 2 Left Ventricular Systolic Dysfunction	1/17 (5.9%)
Gastrointestinal disorders
Grade 2 dysphagia and hypothyroidism	1/17 (5.9%)
Hospitalization for grade 3 GI Bleed	1/17 (5.9%)
General disorders
Grade 4 fatigue	1/17 (5.9%)
Death not associated with CTCAE term	3/17 (17.6%)
Grade 2 Rigors/chills	1/17 (5.9%)
Investigations
Grade 2 Hypothyroidism	1/17 (5.9%)
Grade 3 ALT, gr 2 AST and gr 2 alkaline phosphatase	1/17 (5.9%)
Hospitalization for gr 4 platelets and gr 3 hemoglobin	1/17 (5.9%)
Grade 3 AST	1/17 (5.9%)
Nervous system disorders
Grade 2 somnolence	1/17 (5.9%)
Respiratory, thoracic and mediastinal disorders
Hospitalization for Grade 3 dyspnea	1/17 (5.9%)
Skin and subcutaneous tissue disorders
Hospitalization for infected lymphoma lesion (skin: cellulitis grade 5)	1/17 (5.9%)
Other (Not Including Serious) Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Blood and lymphatic system disorders
Hemorrhage pulmonary Nose	3/17 (17.6%)
Hemorrhage, GI Oral cavity	1/17 (5.9%)
Hemorrhage, GI Stomach	1/17 (5.9%)
Edema: limb	4/17 (23.5%)
Lymphatics - Other	2/17 (11.8%)
Cardiac disorders
Supraventricular arrhythmia Sinus tachycardia	1/17 (5.9%)
Hypertension	4/17 (23.5%)
Hypotension	1/17 (5.9%)
Left ventricular systolic dysfunction	1/17 (5.9%)
Pericardial effusion	1/17 (5.9%)
Endocrine disorders
Hypothyroidism	2/17 (11.8%)
Eye disorders
Diplopia	1/17 (5.9%)
Gastrointestinal disorders
Anorexia	11/17 (64.7%)
Constipation	9/17 (52.9%)
Dehydration	3/17 (17.6%)
Diarrhea	8/17 (47.1%)
Distension	1/17 (5.9%)
Dry mouth	3/17 (17.6%)
Dysphagia	2/17 (11.8%)
Heartburn	8/17 (47.1%)
Mucositis (clinical exam) Oral cavity	4/17 (23.5%)
Mucositis (functional/symptomatic) Oral cavity	4/17 (23.5%)
Mucositis (functional/symptomatic) Pharynx	1/17 (5.9%)
Nausea	9/17 (52.9%)
Taste alteration	4/17 (23.5%)
Vomiting	7/17 (41.2%)
GI - Other	2/17 (11.8%)
General disorders
Fatigue	14/17 (82.4%)
Fever	4/17 (23.5%)
Insomnia	3/17 (17.6%)
Rigors/chills	2/17 (11.8%)
Sweating	2/17 (11.8%)
Pain Abdomen NOS	6/17 (35.3%)
Pain Back	5/17 (29.4%)
Pain Bladder	1/17 (5.9%)
Pain Bone	1/17 (5.9%)
Pain Chest/thorax NOS	1/17 (5.9%)
Pain Extremity-limb	3/17 (17.6%)
Pain Head/headache	3/17 (17.6%)
Pain Joint	3/17 (17.6%)
Pain Lymph node	1/17 (5.9%)
Pain Middle ear	1/17 (5.9%)
Pain Muscle	2/17 (11.8%)
Pain Oral cavity	4/17 (23.5%)
Pain Pain NOS	1/17 (5.9%)
Pain Tumor pain	2/17 (11.8%)
Cough	6/17 (35.3%)
Dyspnea	8/17 (47.1%)
Pleural effusion	2/17 (11.8%)
Voice changes	2/17 (11.8%)
Pulmonary - Other	1/17 (5.9%)
Infections and infestations
Infection with normal ANC Bladder	1/17 (5.9%)
Infection with normal ANC Lung	1/17 (5.9%)
Infection with normal ANC Pelvis NOS	1/17 (5.9%)
Infection with normal ANC Skin	1/17 (5.9%)
Infection with normal ANC Upper airway NOS	1/17 (5.9%)
Infection with unknown ANC Blood	1/17 (5.9%)
Infection with unknown ANC Lip/perioral	1/17 (5.9%)
Infection - Other	1/17 (5.9%)
Musculoskeletal and connective tissue disorders
Arthritis	1/17 (5.9%)
Gait/walking	1/17 (5.9%)
Muscle weakness Whole body/generalized	1/17 (5.9%)
Nervous system disorders
Confusion	1/17 (5.9%)
Mood alteration Anxiety	1/17 (5.9%)
Mood alteration Depression	1/17 (5.9%)
Neuropathy-sensory	7/17 (41.2%)
Somnolence	1/17 (5.9%)
Renal and urinary disorders
Urinary frequency	1/17 (5.9%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/17 (5.9%)
Skin and subcutaneous tissue disorders
Decubitus	1/17 (5.9%)
Hand-foot	1/17 (5.9%)
Nail changes	1/17 (5.9%)
Pruritus	1/17 (5.9%)
Rash	1/17 (5.9%)
Vascular disorders
Thrombosis/thrombus/embolism	1/17 (5.9%)

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.