A Phase I Trial of Combination Bryostatin-1 and Vincristine in HIV-Related B-cell Neoplasms

Inclusion Criteria:

- Histologically confirmed B-cell lymphoma

- Eligible subtypes:

- Intermediate or high-grade non-Hodgkin's lymphoma (NHL), defined as
follicular large cell, mantle cell, diffuse mixed cell, diffuse large cell
and variants, Burkitt or Burkitt-like, or unclassifiable aggressive
histologies

- Body cavity-based lymphoma or primary effusion lymphoma

- Evidence of HIV infection

- Received at least 1 prior systemic chemotherapy regimen with failure to respond or
relapse after completion of first-line therapy, including one of the following
doxorubicin-based combinations:

- Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)

- Infusional cyclophosphamide, doxorubicin, and etoposide (CDE)

- Etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH)

- Evaluable disease outside of prior radiation port

- No CNS parenchymal or leptomeningeal involvement

- No primary CNS NHL

- No HTLV-1-associated leukemia or lymphoma

- Performance status - Karnofsky 70-100%

- At least 12 weeks

- Absolute granulocyte count at least 1,000/mm3

- Platelet count at least 75,000/mm3

- Hemoglobin at least 8.0 g/dL

- Bilirubin no greater than 1.5 mg/dL (unless concurrently on indinavir)

- SGOT and SGPT less than 3 times upper limit of normal

- Creatinine no greater than 1.5 mg/dL

- Creatinine clearance at least 50 mL/min

- No history of cardiac disease

- LVEF at least 45% by radionuclide ventriculography

- No symptomatic congestive heart failure

- No active angina pectoris

- No uncontrolled hypertension

- No history of symptomatic pulmonary disease

- Corrected DLCO more than 50% predicted

- No severe chronic obstructive lung disease

- No symptomatic restrictive lung disease

- Recurrent controllable infection (e.g., thrush) on chronic suppressive therapy
allowed

- No active uncontrolled infection

- No active significant opportunistic infection (e.g., acute Pneumocystis pneumonia,
cytomegalovirus retinitis on induction or maintenance therapy, acute toxoplasmosis)

- No grade 2 or greater peripheral neuropathy

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception

- At least 24 hours since prior transfusion

- At least 24 hours since prior colony-stimulating factor therapy

- No concurrent prophylactic filgrastim (G-CSF)

- See Disease Characteristics

- No concurrent hydroxyurea

- See Disease Characteristics

- At least 4 weeks since prior large-field radiotherapy

- At least 3 weeks since prior anticancer therapy and recovered

- Must be receiving stable antiretroviral regimen of at least 4 weeks duration