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

Phase 1
18 Years
Not Enrolling
AIDS-related Diffuse Large Cell Lymphoma, AIDS-related Diffuse Mixed Cell Lymphoma, AIDS-related Peripheral/Systemic Lymphoma, AIDS-related Small Noncleaved Cell Lymphoma

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Trial Information

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


I. Determine the maximum tolerated dose of bryostatin 1 when administered with vincristine
in patients with recurrent or refractory HIV-related B-cell lymphoma.

II. Determine the toxicity profile of this regimen in these patients. III. Determine the
objective response and survival of these patients treated with this regimen.

IV. Determine the immunomodulatory effects of this regimen on interleukin-2 (IL-2), IL-2
receptor, and IL-6 cytokine levels in these patients.

V. Determine the effect of this regimen on CD4+ lymphocyte count and HIV load in these

VI. Determine the effect of this regimen on the human herpes virus-8 load in these patients
with body cavity-based lymphoma.

OUTLINE: This is a multicenter, dose-escalation study of bryostatin 1.

Patients receive bryostatin 1 IV continuously on days 1 and 15 and vincristine IV over 5
minutes on days 2 and 16. Treatment continues every 4 weeks for a minimum of 2 courses in
the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bryostatin 1 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity.

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD of bryostatin-1 defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Scot Remick

Investigator Role:

Principal Investigator

Investigator Affiliation:

AIDS Associated Malignancies Clinical Trials Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

November 2001

Completion Date:

Related Keywords:

  • AIDS-related Diffuse Large Cell Lymphoma
  • AIDS-related Diffuse Mixed Cell Lymphoma
  • AIDS-related Peripheral/Systemic Lymphoma
  • AIDS-related Small Noncleaved Cell Lymphoma
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, AIDS-Related



AIDS - Associated Malignancies Clinical Trials Consortium Rockville, Maryland  20850