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.
- 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
- Determine the antitumor response in patients treated with this regimen.
- 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.
- 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
- No known neoplastic leptomeningeal involvement and/or brain metastases
- 18 and over
- ECOG 0-2 OR
- Karnofsky 60-100%
- More than 3 months
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 50,000/mm^3
- WBC ≥ 3,000/mm^3
- 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)
- Creatinine normal OR
- Creatinine clearance ≥ 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- 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
- 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:
- See Disease Characteristics
- See Radiotherapy
- At least 12 weeks since prior rituximab
- More than 4 weeks since prior immunotherapy and recovered
- No more than 3 prior chemotherapy regimens
- More than 4 weeks since prior chemotherapy and recovered
- No concurrent glucocorticoids
- At least 12 weeks since prior radioimmunotherapy
- More than 4 weeks since prior radiotherapy and recovered
- Not specified
- At least 4 weeks since prior therapy for the malignancy
- No other concurrent anticancer therapy
- No other concurrent investigational agents