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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00058305
First received: April 7, 2003
Last updated: January 9, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
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
Drug: bryostatin 1
Drug: vincristine sulfate
Other: laboratory biomarker analysis
Phase 2

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response in terms of sustained increase in apoptotic fractions [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response duration [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be analyzed using Kaplan-Meier methods.

  • Incidence of greater than or equal to grade 3 myelotoxicity [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 28
Study Start Date: March 2003
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bryostatin 1, vincristine sulfate)

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.

Drug: bryostatin 1
Given IV
Other Names:
  • B705008K112
  • BRYO
  • Bryostatin
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00058305

Locations
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Investigators
Principal Investigator: Brenda Cooper Case Western Reserve University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00058305     History of Changes
Other Study ID Numbers: NCI-2012-03116, ICC 2402, U01CA062502
Study First Received: April 7, 2003
Last Updated: January 9, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Mantle-Cell
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Vincristine
Bryostatin 1
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2014