Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed relapsed or refractory indolent non-Hodgkin lymphoma (NHL)

- Histological assessment must be confirmed by an independent laboratory prior to
study randomization

- Slides from a biopsy or tissue blocks suitable for review must be available

- Tissue samples may be from the original diagnostic specimen if samples were
obtained within the past 24 months, or may be from a biopsy at the time of
study entry

- Re-biopsy must be done prior to study randomization for patients with signs
of rapid progression (i.e., lactate dehydrogenase [LDH] level ≥ 2 times
upper limit of normal [ULN])

- Any stage disease (with or without B symptoms), including the following:

- Grade I or II follicular lymphoma, defined as follows:

- Grade I follicular center cell lymphoma (formerly known as follicular small
cleaved)

- Grade II follicular center cell lymphoma (formerly known as follicular
mixed)

- Small lymphocytic lymphoma or chronic lymphocytic leukemia (CLL)

- Patients with CLL must have lymph node involvement that is measurable by
radiographic techniques

- Extranodal marginal zone B-cell lymphoma (excluding gastric MALT)

- Nodal marginal zone B-cell lymphoma (monocytoid B-cell lymphoma)

- Splenic marginal zone lymphoma (splenic lymphoma with various lymphocytes)

- CD20+ lymphoma (confirmed by immunochemistry)

- Measurable disease

- At least one objectively bidimensionally measurable lesion as demonstrated by CT
scan, spiral CT scan, PET/CT scan, or MRI, that can be followed for response as
a target lesion

- Patients with only skin lesions or only palpable lymph nodes are not eligible

- Patients with spleen or bone marrow as only site of disease are not eligible

- Patients must have received at least 1 prior therapy

- Prior treatment with fludarabine phosphate, doxorubicin, and/or mitoxantrone is
allowed provided there was a response to treatment (complete response [CR],
unconfirmed complete response [CRu], or partial response [PR]) that lasted ≥ 8
months from the start of that therapy

- Patients refractory to treatments other than anthracycline/anthracenedione,
fludarabine phosphate, or rituximab-containing regimens may be eligible for this
study

- No HIV-related lymphoma

- No active CNS involvement based on clinical evaluation

- If the patient requires a diagnostic lumbar puncture due to high risk criteria
(i.e., sinus involvement, high LDH, high International Prognostic Index score,
or bone marrow involvement), intrathecal chemotherapy (which may include
methotrexate, cytarabine, and corticosteroids) may be administered according to
institutional standards

PATIENT CHARACTERISTICS:

- Life expectancy ≥ 3 months

- ECOG performance status 0-1

- LVEF ≥ 50% by MUGA scan

- Creatinine ≤ 1.5 times ULN

- Total bilirubin ≤ 1.5 times ULN (CTC grade 1) (patients with Gilbert's syndrome or
other hereditary bilirubin defects may be eligible regardless of bilirubin levels)

- AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN if there is hepatic involvement with
lymphoma)

- ANC ≥ 1,500/mm³ (≥ 500/mm³ if bone marrow is involved)

- Platelet count ≥ 75,000/mm³ (with no bleeding)

- No known hypersensitivity to the study drugs or to their excipients

- No known type I hypersensitivity or anaphylactic reactions to murine proteins or to
any component of rituximab

- No clinically significant cardiovascular abnormalities (i.e., NYHA class III-IV heart
disease), including myocardial infarction within the past 6 months, severe
arrhythmia, uncontrolled hypertension, or congestive heart failure requiring current
active therapy

- No concurrent serious (NCI CTCAE grade 3-4) infection, including infection requiring
oral antibiotics or deep-seated or systemic mycotic infections

- No clinical symptoms suggesting unresolved HIV, hepatitis B, or hepatitis C virus
infection

- Patients with seropositivity presumed to be due to prior vaccination against
hepatitis B virus or resolved infection are eligible

- No history of another malignancy except curatively treated basal cell or squamous
cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer
from which the patient is currently in remission, or any other cancer from which the
patient has been disease-free for 5 years

- No other condition that, in the judgment of the investigator, would place the patient
at undue risk, interfere with the results of the study, or make the patient otherwise
unsuitable for the study

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for 6 months after the
completion of study treatment

PRIOR CONCURRENT THERAPY:

- Recovered from all acute toxicities from prior therapies (except alopecia or grade 1
peripheral neuropathy)

- No prior treatment with a cumulative dose of doxorubicin equivalent exceeding 450
mg/m²

- More than 4 weeks since prior radiotherapy, chemotherapy, or other therapies for NHL

- More than 5 days since prior systemic corticosteroids for treatment of NHL

- More than 3 months since prior radioimmunotherapy

- More than 4 weeks since prior major thoracic and/or abdominal surgery and recovered

- More than 1 week since prior minor surgery and recovered

- More than 30 days since prior and no other concurrent investigational drugs

- Concurrent corticosteroids (equivalent of 10 mg of prednisone or less per day)
allowed provided they are only used to treat concurrent disease (other than NHL)

- No other concurrent systemic anticancer therapy

- No concurrent radiotherapy to target lesions

- Concurrent palliative radiotherapy to preexisting stable sites of nonmeasurable
disease allowed