search
Back to results

Bryostatin and Vincristine in B-Cell Malignancies

Primary Purpose

Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
bryostatin 1
vincristine sulfate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Adult Burkitt Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Case Western Reserve University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (bryostatin 1, vincristine sulfate)

Arm Description

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 MTD is determined. The MTD is defined as the dose preceding that at which at least 1 of 3 patients experience dose-limiting toxicity.

Outcomes

Primary Outcome Measures

MTD
Response rates

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
January 10, 2013
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00003166
Brief Title
Bryostatin and Vincristine in B-Cell Malignancies
Official Title
A Phase I Trial of Combination Bryostatin 1 (NSC 339555) and Vincristine in B-Cell Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
May 1998 (undefined)
Primary Completion Date
July 2001 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase I trial is studying the side effects and best dose of bryostatin-1 when given together with vincristine in treating patients with chronic lymphocytic leukemia, non-Hodgkin's lymphoma, or multiple myeloma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells
Detailed Description
PRIMARY OBJECTIVES: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (bryostatin 1, vincristine sulfate)
Arm Type
Experimental
Arm Description
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 MTD is determined. The MTD is defined as the dose preceding that at which at least 1 of 3 patients experience dose-limiting toxicity.
Intervention Type
Drug
Intervention Name(s)
bryostatin 1
Other Intervention Name(s)
B705008K112, BRYO, Bryostatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Other Intervention Name(s)
leurocristine sulfate, VCR, Vincasar PFS
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
MTD
Time Frame
2 weeks
Title
Response rates
Time Frame
Up to 11 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 contraception In women of child-bearing age, a pregnancy test may be done at the discretion of the investigator 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brenda Cooper
Organizational Affiliation
Case Western Reserve University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Bryostatin and Vincristine in B-Cell Malignancies

We'll reach out to this number within 24 hrs