• Maximum tolerated dose (MTD) and toxicity of apolizumab [ Designated as safety issue: Yes ]
• Antitumor activity at the MTD at the end of study treatment [ Designated as safety issue: Yes ]
• Pharmacokinetics [ Designated as safety issue: No ]

• Maximum tolerated dose (MTD) and toxicity of apolizumab
• Antitumor activity at the MTD at the end of study treatment
• Pharmacokinetics

• Effects of treatment in patients with chronic lymphocytic leukemia (CLL) as measured by microarray profiling pre-treatment and at the end of study treatment [ Designated as safety issue: No ]
• Effects of treatment in patients with CLL on kinetics of apoptosis as measured by fluorescent-activated cell sorting (FACS) analysis of Annnexin 5 pre-treatment and at the end of study treatment [ Designated as safety issue: No ]
• Effects of treatment on T-cell and B-cell levels pre-treatment, during treatment, and at the end of study treatment [ Designated as safety issue: No ]

• Effects of treatment in patients with chronic lymphocytic leukemia (CLL) as measured by microarray profiling pre-treatment and at the end of study treatment
• Effects of treatment in patients with CLL on kinetics of apoptosis as measured by fluorescent-activated cell sorting (FACS) analysis of Annnexin 5 pre-treatment and at the end of study treatment
• Effects of treatment on T-cell and B-cell levels pre-treatment, during treatment, and at the end of study treatment

RATIONALE: Monoclonal antibodies such as apolizumab and rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of combining apolizumab and rituximab in treating patients who have lymphoma, Waldenstrom's macroglobulinemia, or chronic lymphocytic leukemia.

OBJECTIVES:

• Determine the maximum tolerated dose of apolizumab when administered with rituximab in patients with relapsed CD20 and 1D10-positive B-cell lymphoma, Waldenstrom's macroglobulinemia, or chronic lymphocytic leukemia.
• Determine the toxicity of this regimen in these patients.
• Determine the antitumor activity of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation study of apolizumab.

Patients receive apolizumab IV over several hours on day 1 followed 24-36 hours later by rituximab IV. Treatment repeats every 7 days for 4 weeks. At 12 weeks after completion of treatment, patients with stable disease or a complete or partial response may receive additional treatment for up to 3 courses.

Cohorts of 2-6 patients receive escalating doses of apolizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 24 additional patients (12 with chronic lymphocytic leukemia or Waldenstrom's macroglobulinemia and 12 with lymphoma) are treated at the MTD.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 6-69 patients will be accrued for this study within 12 months.

• Leukemia
• Lymphoma

• Biological: apolizumab
• Biological: rituximab

DISEASE CHARACTERISTICS:

• Histologically and immunophenotypically confirmed B-cell lymphoma, Waldenstrom's macroglobulinemia, or chronic lymphocytic leukemia
• CD20 and 1D10-positive by immunohistochemistry or fluorescence-activated cell sorting
• Received at least 1 prior systemic treatment regimen
• Ineligible for potentially curative therapy (i.e., transplantation)
• No active CNS lymphoma

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 500/mm^3*
• Platelet count at least 75,000/mm^3* NOTE: * Unless due to lymphoma

Hepatic:

• Bilirubin less than 2 mg/dL (5 mg/dL in case of Gilbert's syndrome defined as more than 80% unconjugated)*
• SGPT less than 5 times upper limit of normal* NOTE: * Unless due to lymphoma

Renal:

• Creatinine no greater than 1.5 mg/dL* OR
• Creatinine clearance greater than 60 mL/min* NOTE: * Unless due to lymphoma

Cardiovascular:

• No active cardiac disease
• No active cerebrovascular disease
• No active peripheral arterial vascular disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 month since prior rituximab
• No prior apolizumab

Chemotherapy:

• More than 3 weeks since prior systemic cytotoxic chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• More than 1 week since prior systemic steroids (except stable doses of less than 10 mg/day)

Radiotherapy:

• Not specified

Surgery:

• Not specified