• Feasability and safety [ Designated as safety issue: Yes ]
• Antitumor response [ Designated as safety issue: No ]

• Feasability and safety
• Antitumor response

• Functional and molecular status of effector cells [ Designated as safety issue: No ]
• Expression of CD20 and complement-inhibitory molecules on tumor cells before and after treatment [ Designated as safety issue: No ]
• Effects on global gene expression pattern in chronic lymphocytic leukemia cells [ Designated as safety issue: No ]

• Functional and molecular status of effector cells
• Expression of CD20 and complement-inhibitory molecules on tumor cells before and after treatment
• Effects on global gene expression pattern in chronic lymphocytic leukemia cells

RATIONALE: Drugs used in chemotherapy, such as bryostatin 1, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Bryostatin 1 may help rituximab kill more cancer cells by making them more sensitive to the drug.

PURPOSE: This phase II trial is studying how well giving bryostatin 1 together with rituximab works in treating patients with B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia that has not responded to previous treatment with rituximab.

OBJECTIVES:

Primary

• Determine the feasibility and safety of bryostatin 1 and rituximab in patients with rituximab-refractory indolent B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia (CLL).
• Determine the antitumor response in patients treated with this regimen.

Secondary

• Determine the effects of this regimen on the functional and molecular status of effector cells (i.e., NK cells, monocytes, and dendritic cells) in these patients.
• Determine the expression of CD20 and complement-inhibitory molecules on tumor cells before and after treatment with this regimen in these patients.
• Determine the effects of this regimen on the global gene expression pattern in CLL cells of these patients.

OUTLINE: This is a multicenter study.

Patients receive bryostatin 1 IV continuously over 24 hours on days -6, 2, and 9 of course 1 and on days 2 and 9 of courses 2-6. Patients also receive rituximab IV over 4 hours on days 1, 8, 15, and 22 of courses 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: Approximately 18-48 patients (9-24 with non-Hodgkin's lymphoma and 9-24 with chronic lymphocytic leukemia) will be accrued for this study within 12-30 months.

• Leukemia
• Lymphoma

• Biological: rituximab
• Drug: bryostatin 1

DISEASE CHARACTERISTICS:

• One of the following histologically or cytologically confirmed diseases:

  • Indolent B-cell non-Hodgkin's lymphoma (NHL)

    • Stage II-IV disease

  • Chronic lymphocytic leukemia (CLL) meeting 1 of the following risk criteria:

    • Intermediate-risk with progressive disease
    • High-risk, modified Rai stage disease
• CD20-positive by flow cytometry or immunohistochemistry
• Measurable disease
• Rituximab-refractory disease, defined as failure to achieve a response to the last course of prior treatment with rituximab alone or in combination with other therapeutic modalities
• No known neoplastic leptomeningeal involvement and/or brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 50,000/mm^3
• WBC ≥ 3,000/mm^3

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal
• Bilirubin normal (unless due to Gilbert's disease or organ involvement by NHL or CLL)

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative

• No history of anaphylaxis or immunoglobulin (Ig) E-mediated hypersensitivity to murine protein

  • Prior infusion reactions to rituximab without an IgE component allowed
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• See Radiotherapy
• At least 12 weeks since prior rituximab
• More than 4 weeks since prior immunotherapy and recovered

Chemotherapy

• No more than 3 prior chemotherapy regimens
• More than 4 weeks since prior chemotherapy and recovered

Endocrine therapy

• No concurrent glucocorticoids

Radiotherapy

• At least 12 weeks since prior radioimmunotherapy
• More than 4 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• At least 4 weeks since prior therapy for the malignancy
• No other concurrent anticancer therapy
• No other concurrent investigational agents