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