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

• 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 ]
  

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.

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