Bryostatin and Vincristine in B-Cell Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003166
First received: November 1, 1999
Last updated: January 10, 2013
Last verified: January 2013
  Purpose

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


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

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • MTD [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
  • Response rates [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: May 1998
Primary Completion Date: July 2001 (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 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.

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  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: NCT00003166

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: NCT00003166     History of Changes
Other Study ID Numbers: NCI-2012-03120, CWRU 3Y97, U01CA062502
Study First Received: November 1, 1999
Last Updated: January 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Burkitt Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Neoplasms, Experimental
Leukemia
Leukemia, B-Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias

ClinicalTrials.gov processed this record on September 16, 2014