RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bevacizumab may also stop the growth of cancer cells by blocking blood flow to the cancer. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with several chemotherapy drugs (combination chemotherapy) works in treating patients with peripheral T-cell lymphoma or natural killer cell neoplasms.

OBJECTIVES:

Primary

• Determine the 12-month progression-free survival of patients with peripheral T-cell or natural killer cell neoplasms treated with bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP).

Secondary

• Determine the overall response rate (complete remission [CR, unconfirmed CR, or functional CR] and partial remission) in these patients after courses 3, 6, and 8 of this treatment regimen.
• Determine the overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive 6-8 cycles of A-CHOP followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 [max. 2 mg]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.

After completion of study treatment, patients are followed every 3 months for 2 years, and then every 6 months for up to 5 years.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study within 22 months.

ACTUAL ACCRUAL: 46

INCLUSION CRITERIA:

• Diagnosis of peripheral T-cell or natural killer cell neoplasm

  • Any stage disease allowed
  • HTLV-positive tumors allowed

• At least one objective measurable disease parameter. Abnormal positron emission tomography scans are not considered evidence of measurable disease unless results are confirmed by CT scan or other appropriate imaging techniques

• Age 18 and over

• ECOG Performance status 0-2

• Absolute neutrophil count ≥ 1,000/mm^3(500/mm^3 if due to bone marrow involvement with lymphoma)

• Platelet count ≥ 100,000/mm^3(50,000/mm^3 if due to bone marrow involvement with lymphoma)

• Bilirubin ≤ 2.0 mg/dL (≤ 3 times upper limit of normal [ULN] if due to hepatic involvement with lymphoma)

• AST ≤ 2 times ULN (5 times ULN if due to hepatic involvement with lymphoma)

• PT, INR, and PTT ≤ 1.5 times normal

• Creatinine ≤ 2.0 mg/dL

• Urinary protein:creatinine ratio ≤ 1

• History of deep venous thrombosis allowed provided patient is on a stable dose of anticoagulants for at least 2 weeks prior to study entry

• LVEF ≥ 50%

• History of pulmonary embolism allowed provided patient is on a stable dose of anticoagulants for at least 2 weeks prior to study entry

• One prior cycle of CHOP for PTCL allowed

• More than 4 weeks since prior major invasive surgery or open biopsy

• At least 7 days since prior minor surgery. Peripheral lymph node core biopsy, bone marrow biopsy, fine needle aspiration, skin biopsy, or central line placement are not considered minor surgical procedures

• More than 7 days since prior and no concurrent anti-platelet drugs (e.g., ticlopidine, clopidogrel, or cilostazol) except aspirin or other nonsteroidal anti-inflammatory drugs

• Concurrent anticoagulants allowed provided patient is on a stable dose

  • INR must be stable for at least 2 weeks prior to study entry
  • PT/INR and/or PTT must be closely monitored and levels kept within acceptable range for underlying thrombotic disease
  • Concurrent heparin flush for maintenance of central line patency allowed

EXCLUSION CRITERIA:

• Anaplastic lymphoma kinase (ALK)-positive T-cell large cell lymphoma. ALK-negative T-cell large cell lymphoma allowed
• Cutaneous T-cell lymphoma
• History of or current radiographic evidence of CNS metastasis, including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement
• Evidence of bleeding diathesis or coagulopathy
• Cerebrovascular accident within the past 6 months
• Myocardial infarction within the past 6 months
• Unstable angina within the past 6 months
• New York Heart Association class II-IV congestive heart failure
• Uncontrolled hypertension (i.e., systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 100 mm Hg)
• Other clinically significant cardiovascular or peripheral vascular disease
• Abdominal fistula within the past 6 months
• Gastrointestinal perforation within the past 6 months
• Intra-abdominal abscess within the past 6 months
• Concurrent major surgery
• Pregnant or nursing. Female patients must have negative pregnancy test. Fertile patients must use effective contraception
• History of active seizures
• Significant traumatic injury within the past 4 weeks
• Non-healing ulcer (unless involved with lymphoma)
• Bone fracture
• Active infection requiring parenteral antibiotics
• HIV positivity
• Other active malignancy within the past 6 months except carcinoma in situ of the cervix or basal cell carcinoma of the skin