Bryostatin and Vincristine in B-Cell Malignancies
Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: 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
Intervention: bryostatin 1 (Drug); vincristine sulfate (Drug); laboratory biomarker analysis (Other)
Phase: Phase 1
Status: Completed
Sponsored by: National Cancer Institute (NCI) Official(s) and/or principal investigator(s): Brenda Cooper, Principal Investigator, Affiliation: Case Western Reserve University
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
Clinical Details
Official title: A Phase I Trial of Combination Bryostatin 1 (NSC 339555) and Vincristine in B-Cell Malignancies
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: MTDResponse rates
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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)
Locations and Contacts
Case Western Reserve University, Cleveland, Ohio 44106, United States
Additional Information
Starting date: May 1998
Last updated: January 10, 2013
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