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