ClinicalTrials.gov processed this data on March 28, 2024Link to the current ClinicalTrials.gov record.https://clinicaltrials.gov/ct2/show/NCT00003166NCI-2012-03120CWRU 3Y97U01CA062502NCT00003166Bryostatin and Vincristine in B-Cell MalignanciesA Phase I Trial of Combination Bryostatin 1 (NSC 339555) and Vincristine in B-Cell MalignanciesNational Cancer Institute (NCI)NIH
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
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.
CompletedMay 1998July 2001Phase 1InterventionalNoN/ASingle Group AssignmentTreatmentNone (Open Label)MTD2 weeksResponse ratesUp to 11 years118Recurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRefractory Chronic Lymphocytic LeukemiaRefractory Multiple MyelomaStage III Multiple MyelomaTreatment (bryostatin 1, vincristine sulfate)ExperimentalPatients 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.Drugbryostatin 1Given IVTreatment (bryostatin 1, vincristine sulfate)B705008K112BRYOBryostatinDrugvincristine sulfateGiven IVTreatment (bryostatin 1, vincristine sulfate)leurocristine sulfateVCRVincasar PFSOtherlaboratory biomarker analysisCorrelative studiesTreatment (bryostatin 1, vincristine sulfate)
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)
All18 YearsN/ANoBrenda CooperPrincipal InvestigatorCase Western Reserve UniversityCase Western Reserve UniversityClevelandOhio44106United StatesUnited StatesJanuary 2013November 1, 1999March 18, 2004March 19, 2004January 10, 2013January 10, 2013January 11, 2013SponsorBurkitt LymphomaLymphomaMultiple MyelomaNeoplasms, Plasma CellLymphoma, Non-HodgkinLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Mantle-CellPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Large-Cell, ImmunoblasticPlasmablastic LymphomaRecurrenceVincristineBryostatin 1