Study: Treatment of Relapsed Lymphoid Malignancies With an Anti-Angiogenic Approach

Phase II Study: Treatment of Relapsed Lymphoid Malignancies With an Anti-angiogenic Approach

1.1 To determine the efficacy of a combination treatment of VP-16, chlorambucil, dexamethasone, and vincristine in patients with relapsed/refractory hematological malignancies.

1.2 To determine the toxicity profile of the above regimen in this patient population.

1.3 Evaluate the effect of low dose administration of chemotherapy on angiogenesis, and correlate this with tumor responses.

The purpose of the study is to see how effective the combination of chemotherapy drugs VP-16, chlorambucil, dexamethasone, and vincristine is for patients who have blood cancers that have returned or not responded to prior treatment. Some patients may also receive a medication called rituximab if their doctor thinks it is appropriate. This drug combination will be given to study participants in a low dose continuous basis. The study will also collect information about the side effects of the above drug combination on patients with these types of cancers. Previous studies on patients with non-Hodgkin's lymphoma indicate that some patients treated with this drug combination achieved a high response. The aim of this study is to test this drug combination in a controlled setting.

Inclusion Criteria:

• All patients, 18 years of age or older, with Hodgkin's lymphoma, Non-Hodgkin lymphoma (NHL), multiple myeloma (MM), or chronic lymphocytic leukemia (CLL) are eligible.
• Patients must have a life expectancy of at least 12 weeks.
• Patients must have a Zubrod performance status of 0-2.
• Patients must sign an informed consent.
• Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of > 1,000 or cells/mm3 and platelet count >50,000/mm3 and absence of a regular red blood cell or platelet transfusion requirement.
• Patients should have adequate hepatic function with a total bilirubin < 2 mg/dl and SGOT or SGPT < two times the upper limit of normal, and adequate renal function as defined by a serum creatinine < 2.0 x upper limit of normal.
• Patients must have received at least two previous chemotherapy regimens for their disease.
• Patients must have measurable disease (NHL) or evaluable disease (MM, CLL).

Exclusion Criteria:

• Patients with symptomatic brain metastases are excluded from this study.
• Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception.
• Patients may receive no other concurrent chemotherapy or radiation therapy during this trial.
• Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial.