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

Inclusion Criteria

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