Rituximab and Liposomal Doxorubicin in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

OBJECTIVES:

Primary

- Determine the safety, including qualitative and quantitative toxic effects and their
duration and reversibility, of rituximab and doxorubicin HCl liposome in patients with
relapsed or refractory, indolent or aggressive CD20-positive B-cell non-Hodgkin's
lymphoma.

Secondary

- Determine the efficacy, including overall response rate and durability of objective
response, of this regimen in these patients.

- Correlate pretreatment functional, phenotypic, and genotypic characteristics of host
immune effector cells with response in patients treated with this regimen.

OUTLINE: This is an open-label, pilot study.

Patients receive rituximab IV over 3-8 hours on day 1 and doxorubicin HCl liposome IV over
1-3 hours on day 3. Treatment repeats every 21 days for 6 courses in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 4 years.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following indolent or aggressive B-cell non-Hodgkin's lymphoma
(NHL) subtypes:

- Grade 1-3 follicular lymphoma

- Mantle cell lymphoma

- Small lymphocytic lymphoma

- Diffuse large B-cell lymphoma

- Diffuse mixed cell lymphoma

- Marginal zone lymphoma

- Relapsed or refractory CD20-positive disease

- Measurable disease

- Must have received ≥ 1 but < 4 prior standard chemotherapy regimens

- No Burkitt's lymphoma or precursor B-lymphoblastic lymphoma

- No CNS lymphoma

PATIENT CHARACTERISTICS:

Performance status

- Karnofsky 60-100%

Life expectancy

- At least 6 months

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 75,000/mm^3

- Hemoglobin > 7 g/dL

Hepatic

- AST or ALT < 2 times upper limit of normal (unless due to primary disease)

- Bilirubin ≤ 2 mg/dL

Renal

- Creatinine ≤ 2.0 mg/dL

Cardiovascular

- LVEF ≥ 50% by MUGA and/or 2-D echocardiogram

- No history of New York Heart Association class II-IV cardiac disease

- No congestive heart failure

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No known HIV positivity

- No uncontrolled active bacterial, viral, or fungal infection

- No other serious disease that would preclude study participation

- No other primary malignancy within the past 5 years except squamous cell or basal
cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Recovered from prior immunotherapy

- Prior immunotherapy, including rituximab or other monoclonal antibody, allowed

Chemotherapy

- See Disease Characteristics

- More than 4 weeks since prior chemotherapy and recovered

- No prior doxorubicin (or equivalent anthracycline) at a cumulative dose > 400 mg/m^2

- No other concurrent chemotherapy

Endocrine therapy

- Nonsteroidal hormones for nonlymphoma-related conditions (e.g., insulin for diabetes)
allowed

- No concurrent corticosteroids except for a transient inflammatory reaction (i.e.,
skin rash or hives)

Radiotherapy

- Recovered from prior radiotherapy

- No concurrent radiotherapy

Surgery

- More than 4 weeks since prior major surgery (other than diagnostic surgery) and
recovered

Other

- No other concurrent antitumor agents

- No other concurrent investigational agents