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Bryostatin 1 Plus Vincristine in Treating Patients With Progressive or Relapsed Non-Hodgkin's Lymphoma After Bone Marrow or Stem Cell Transplantation

Primary Purpose

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma

Status
Completed
Phase
Phase 2
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 Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue

Eligibility Criteria

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

Inclusion Criteria: Patients must have biopsy proven relapsed or progressive low or intermediate grade non-Hodgkin's lymphoma (by REAL classification); after prior autologous bone marrow transplantation or peripheral blood stem cell rescue Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan Patients must have received a prior autologous bone marrow or peripheral blood stem cell rescue to be eligible for this trial (there is no specified time interval from transplant prior to enrollment on study; 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 4 weeks and recovered from all treatment related toxicity; prior vincristine therapy is allowed Life expectancy of greater than 8-10 weeks ECOG performance status 0-2 Absolute neutrophil count >= 1,250/uL Platelets >= 50,000/uL Hemoglobin >= 8.5 g /dl Total bilirubin =< 2.0 mg/dl AST(SGOT)/ALT(SGPT) =< 3 X normal Creatinine =< 2.0 mg/dl Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients requiring concomitant anticancer therapy are excluded Patients with known brain metastases or leptomeningeal involvement should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events Patients who have had a prior allogeneic transplant are not eligible Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant and lactating women are excluded from this study HIV infection Patients with clinically apparent neuropathy (>= grade 2)

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 on days 1 and 15 and vincristine IV on days 2 and 16. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients without disease progression after 6 courses may continue therapy with bryostatin 1 IV over 24 hours on days 1 and 22 and vincristine IV on days 2 and 23. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Response in terms of sustained increase in apoptotic fractions

Secondary Outcome Measures

Complete response duration
Will be analyzed using Kaplan-Meier methods.
Incidence of greater than or equal to grade 3 myelotoxicity

Full Information

First Posted
April 7, 2003
Last Updated
January 9, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00058305
Brief Title
Bryostatin 1 Plus Vincristine in Treating Patients With Progressive or Relapsed Non-Hodgkin's Lymphoma After Bone Marrow or Stem Cell Transplantation
Official Title
A Phase II Study of Bryostatin 1 and Vincristine in Patients With Low or Intermediate Grade Non-Hodgkin's Lymphoma Progressing or Relapsing After a Prior Autologous Bone Marrow or Stem Cell Transplant
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
March 2003 (undefined)
Primary Completion Date
December 2007 (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
Phase II trial to study the effectiveness of combining bryostatin 1 with vincristine in treating patients who have progressive or relapsed non-Hodgkin's lymphoma after autologous bone marrow transplantation or autologous stem cell transplantation. Drugs used in chemotherapy such as vincristine use different ways to stop cancer cells from dividing so they stop growing or die. Bryostatin 1 may help vincristine kill more cancer cells by making the cells more sensitive to the drug
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate response rate when bryostatin 1 is given in combination with vincristine in patients with low and intermediate grade non-Hodgkin's lymphoma who have progressed or relapsed following an autologous bone marrow or stem cell transplant. II. To determine if blunting of apoptotic response (with two or more consecutive apoptotic fractions) following treatment using annexin V staining of peripheral blood CD5+ and CD19+ lymphocytes by flow cytometry is predictive of outcome (i.e. lack of clinical response). III. To prospectively evaluate the incidence of > grade 3 myelotoxicity with this regimen. OUTLINE: This is a multicenter study. Patients receive bryostatin 1 IV over 24 hours on days 1 and 15 and vincristine IV on days 2 and 16. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients without disease progression after 6 courses may continue therapy with bryostatin 1 IV over 24 hours on days 1 and 22 and vincristine IV on days 2 and 23. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 2-5 years, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Splenic Marginal Zone Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (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 on days 1 and 15 and vincristine IV on days 2 and 16. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients without disease progression after 6 courses may continue therapy with bryostatin 1 IV over 24 hours on days 1 and 22 and vincristine IV on days 2 and 23. Courses repeat every 6 weeks in the absence of disease progression or unacceptable 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
Response in terms of sustained increase in apoptotic fractions
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Complete response duration
Description
Will be analyzed using Kaplan-Meier methods.
Time Frame
Up to 5 years
Title
Incidence of greater than or equal to grade 3 myelotoxicity
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have biopsy proven relapsed or progressive low or intermediate grade non-Hodgkin's lymphoma (by REAL classification); after prior autologous bone marrow transplantation or peripheral blood stem cell rescue Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan Patients must have received a prior autologous bone marrow or peripheral blood stem cell rescue to be eligible for this trial (there is no specified time interval from transplant prior to enrollment on study; 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 4 weeks and recovered from all treatment related toxicity; prior vincristine therapy is allowed Life expectancy of greater than 8-10 weeks ECOG performance status 0-2 Absolute neutrophil count >= 1,250/uL Platelets >= 50,000/uL Hemoglobin >= 8.5 g /dl Total bilirubin =< 2.0 mg/dl AST(SGOT)/ALT(SGPT) =< 3 X normal Creatinine =< 2.0 mg/dl Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients requiring concomitant anticancer therapy are excluded Patients with known brain metastases or leptomeningeal involvement should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events Patients who have had a prior allogeneic transplant are not eligible Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant and lactating women are excluded from this study HIV infection Patients with clinically apparent neuropathy (>= grade 2)
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 1 Plus Vincristine in Treating Patients With Progressive or Relapsed Non-Hodgkin's Lymphoma After Bone Marrow or Stem Cell Transplantation

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