Sunitinib in Treating Patients With Relapsed or Refractory Diffuse or Mediastinal Large B-Cell Lymphoma
Condition: Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse
Intervention: sunitinib malate
Intervention description: Given orally
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility 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