Know Cancer

forgot password

A Phase I Trial of Combination Bryostatin 1 (NSC 339555) and Vincristine in B-Cell Malignancies

Phase 1
18 Years
Not Enrolling
Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Multiple Myeloma, Stage III Multiple Myeloma

Thank you

Trial Information

A Phase I Trial of Combination Bryostatin 1 (NSC 339555) and Vincristine in B-Cell Malignancies


I. To determine the maximum tolerated dose of bryostatin 1 as a 24 hour infusion and
vincristine when administered sequentially.

II. To determine the effect of this combination on programmed cell death (apoptosis).

III. To determine the immunomodulatory effect of bryostatin 1. IV. To observe patients for
clinical antitumor response after giving combination bryostatin 1 and vincristine.

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

Patients receive bryostatin 1 IV over 24 hours followed immediately by vincristine IV.
Treatment repeats every 2 weeks in the absence of disease progression or unacceptable
toxicity. Patients completing 6 courses of therapy may receive subsequent courses every 3
weeks and then every 4 weeks after 24 months of treatment. Patients may return to a 2- or
3-week treatment course at the discretion of the principal investigator.

Cohorts of 3 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 at least 1
of 3 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

Inclusion Criteria:

- Patients with biopsy proven B-cell malignancies [e.g. chronic lymphocytic leukemia
(CLL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM)]; HIV-associated lymphomas
and acute leukemias are not eligible

- Performance status: ECOG 0, 1, or 2

- Life expectancy of at least 12 weeks

- Patients with aggressive NHL will be enrolled after having failed all possible
therapy with curative intent

- Patients with CLL must have failed an alkylating agent-containing regimen as well as
fludarabine chemotherapy

- Patients with multiple myeloma must have received at least one prior chemotherapy
regimen and not be eligible for a dose intensification treatment approach

- At least 4 weeks must have elapsed since prior large-field radiation therapy

- Patients must have been off previous anti-cancer therapy for at least 3 weeks (6
weeks for BCNU and mitomycin C) and recovered from all treatment related toxicity

- Prior vincristine therapy is allowed

- Sexually active men and women must use an accepted and effective method of

- In women of child-bearing age, a pregnancy test may be done at the discretion of the

- Must have given written informed consent

Exclusion Criteria:

- Patients with brain metastasis, leptomeningeal involvement, primary CNS NHL, and
acute leukemia are ineligible

- Patients with HIV infection are ineligible

- WBC < 3000/ul

- Granulocytes < 1500/ul

- Platelets < 50,000/ul

- Hemoglobin =< 8.5 g/dl

- Bilirubin > 1.5 mg/dl

- AST and ALT > 2 times normal

- Creatinine > 2.0 mg/dl, and/or actual creatinine clearance < 40 ml/min/1.73 m^2; all
patients are required to have a 24 hr creatinine clearance

- Clinical evidence of bleeding diathesis

- ECOG Performance status 3 or 4

- Patients who are pregnant or lactating; vincristine can cause fetal harm

- Patients with clinically apparent neuropathy are ineligible (>= grade 2 neuropathy)

Type of Study:


Study Design:

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

Outcome Measure:


Outcome Time Frame:

2 weeks

Safety Issue:


Principal Investigator

Brenda Cooper

Investigator Role:

Principal Investigator

Investigator Affiliation:

Case Western Reserve University


United States: Food and Drug Administration

Study ID:




Start Date:

May 1998

Completion Date:

Related Keywords:

  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Multiple Myeloma
  • Stage III Multiple Myeloma
  • Burkitt Lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, Mantle-Cell



Case Western Reserve University Cleveland, Ohio  44106