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

Study Overview
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Brief Summary
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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.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the response rate in patients with relapsed or refractory, diffuse or mediastinal, large B-cell lymphoma treated with sunitinib malate. II. 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.

Official Title
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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

Conditions
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Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma

Intervention / Treatment
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* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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<br>* Given orally<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

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