Funding ended when only one subject enrolled and subject withdrew early.

RATIONALE: Drugs used in chemotherapy, such as clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, 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. Giving clofarabine together with rituximab may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with rituximab and to see how well they work in treating patients with relapsed B-cell non-Hodgkin lymphoma.

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of clofarabine in adult patients with relapsed CD20-positive B-cell non-Hodgkin lymphoma (NHL).
• To estimate objective response rates of clofarabine in combination with rituximab in these patients.

Secondary

• To determine the 1-year progression-free survival of this regimen using the mean tolerated dose in these patients.
• To determine the safety and efficacy of this regimen in these patients.
• To determine if clofarabine acts as an inhibitor of DNA methylation similar to cladribine by performing scientific correlates.
• To determine whether response to clofarabine alone or in combination with rituximab correlates with changes in global serum DNA methylation index.
• To identify the gene activated by clofarabine therapy by using genomic DNA and RNA array technology.

OUTLINE: This is a phase I, dose-escalation study of clofarabine followed by a phase II study.

Patients receive oral clofarabine once daily on days 1-14 of all courses and rituximab IV on days 1, 8, 15, and 22 of course one and then on day 1 of courses 2-8. Courses repeat every 4 weeks. After 2 courses of therapy, patients who are eligible for stem cell transplantation may either undergo transplantation or continue receiving study drugs until disease progression or unacceptable toxicity for up to a total of 8 courses of treatment.

Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed to identify global DNA methylation differences and correlate changes in methylation index (MI) with patient outcome after treatment with clofarabine with or without rituximab via high performance liquid chromatography (HPLC); to determine differences in gene expression via microarray analysis and micro-RNA (miRNA) expression via quantitative polymerase chain reaction (PCR) in patients with high compared to low global DNA methylation index and miRNA expression for CD5+ B-lymphocytes obtained from pediatric tonsils and from B-lymphocytes of 5 healthy controls; and to determine gene expression and miRNA profiles in patients before and after treatment with clofarabine with or without rituximab via genomic DNA arrays.

After completion of study treatment, patients are followed once a year for 2 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed B-cell lymphoma

  • Relapsed disease
  • CD20-positive disease

• Must have had bone marrow aspiration and biopsy (uni- or bilateral) within the past 42 days and chest CT and CT of the abdomen and pelvis within the past 28 days

• Documented bidimensionally measurable disease within the past 28 days

  • Patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group(ECOG) performance status 0-2
• Leukocyte count ≥ 3,000/μL
• Absolute neutrophil count ≥ 1,500/μL
• Platelet count ≥ 75,000/μL
• Total bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 30 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after completion of study therapy
• No known AIDS or HIV-associated complex
• No active hepatitis B infection
• No other severe concurrent disease, history of serious organ dysfunction, or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment
• No uncontrolled systemic fungal, bacterial, viral, or other infection, defined as ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment
• No history of intolerance or allergic reactions to clofarabine or rituximab
• No significant concurrent disease, illness, or psychiatric disorder that would compromise the patient's safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
• No concurrent active GI disease that may impair absorption of oral clofarabine

PRIOR CONCURRENT THERAPY:

• Recovered from all previous therapies
• No prior gastrointestinal (GI) surgery that may impair absorption of oral clofarabine
• More than 2 weeks since prior and no concurrent anticancer therapy, except for hydroxyurea
• More than 4 weeks since prior radioimmunotherapy
• More than 1 month since prior investigational agents
• No concurrent cytotoxic therapy or investigational therapy
• No other concurrent investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy
• No concurrent alternative medications (e.g., herbal or botanical for anticancer purposes)
• No other concurrent chemotherapy or immunotherapy
• No concurrent radiotherapy
• No concurrent colony stimulating factors (phase I portion of the study)