A Phase I/II Study of Flavopiridol Administered as a 30-Minute Bolus Followed by a 4-Hour Infusion in Lymphomas and Multiple Myeloma
I. Determine the disease-specific dose-limiting toxicity and maximum tolerated dose of
flavopiridol in patients with relapsed or refractory lymphoma or multiple myeloma.
II. Determine the complete and partial response rate in patients with selected non-Hodgkin's
lymphoma (e.g., indolent B-cell, mantle cell, intermediate grade B-cell, and T/NK-cell),
Hodgkin's lymphoma, or multiple myeloma treated with this drug.
III. Determine the qualitative and quantitative toxic effects or this drug, in terms of
organ specificity, time course, predictability, and reversibility in these patients.
IV. Determine subsets of lymphoid/plasma cell malignancies that are suitable for larger
phase II studies designed to further evaluate the efficacy and toxicity of this drug in
I. Determine the pharmacokinetics of this drug in these patients. II. Determine the effect
of this drug on innate immunity (including T-, B-, and NK-cell subsets) and quantitative
immunoglobulin levels in these patients.
III. Determine whether acute infusion toxicity (e.g., fever, hypotension, tumor pain, and
dyspnea) observed with other flavopiridol treatment schedules is related to a
cytokine-release syndrome in these patients.
IV. Determine whether this drug induces response (independent of p53 mutational status) in
OUTLINE: This is a phase I, dose-escalation study followed by a multicenter, phase II, pilot
study. Patients enrolled in the phase II portion of the study are stratified according to
PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment
repeats every 6 weeks for up to 6 courses in the absence of disease progression or
unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.
NOTE: The phase II treatment dose and schedule for hairy cell leukemia patients will be
adapted from that developed in previous phase II studies of flavopiridol for the treatment
of chronic lymphocytic leukemia.
After completion of study therapy, patients are followed every 3 months for 2 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Disease-specific dose-limiting toxicity and maximum tolerated dose of flavopiridol graded according to the CTCAE version 4.0 (Phase I)
Dose limiting toxicity (DLT) for an individual disease group is defined as 1) any grade 3-4 non-hematologic toxicity (except leukopenia or neutropenia) that does not resolve or decrease to grade 1-2 within 2 weeks, or 2) any grade 4 hematologic toxicity that causes more than a 1 week delay in administration of therapy. The maximum tolerated dose (MTD) is defined as that dose level beneath the dose at which 2 or more of 6 patients experience DLT.
Ohio State University
United States: Food and Drug Administration
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