Bryostatin 1 and Rituximab in Treating Patients With B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase II Trial Of Bryostatin-1 In Combination With Rituximab In Rituximab-Refractory Indolent B-cell Non Hodgkin's Lymphoma And Chronic Lymphocytic Leukemia

Conditions
-----------------
Leukemia, Lymphoma

Intervention / Treatment
-----------------
* Biological: rituximab
* Drug: bryostatin 1


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: rituximab|nan|
|Drug: bryostatin 1|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasability and safety |  |  | 
| Antitumor response |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
contiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, contiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, recurrent grade 1 follicular lymphoma, stage III grade 1 follicular lymphoma, stage IV grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, recurrent grade 2 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 2 follicular lymphoma, contiguous stage II marginal zone lymphoma, noncontiguous stage II marginal zone lymphoma, recurrent marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, refractory chronic lymphocytic leukemia, Waldenström macroglobulinemia, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma