A Phase I/II Study of Flavopiridol in Relapsed or Refractory Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma (DLBCL)
Flavopiridol is a synthetic N-methylpiperidinyl, chlorophenyl flavone compound that targets
a number of different cellular pathways and processes.
It works through several different mechanisms that include inhibition of cyclin dependent
kinases and the cyclin D-1 complex which is over-expressed in mantle cell lymphoma.
Flavopiridol also has demonstrated activity in activated B-like diffuse large B-cell
lymphoma cell lines.
One of the great challenges in developing flavopiridol and applying it clinically has been
determining its optimal dosing schedule. Following several different dosing schedules, one
strategy that has been very promising in chronic lymphocytic leukemia (CLL) is the
application of so-called hybrid schedules of the drug (an infusion for an intermediate time
following a bolus dose).
Assess the toxicity and safety of administration of this hybrid schedule.
Assess the response rate of the hybrid schedule of flavopiridol in relapsed mantle cell
lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL).
Relapsed MCL or DLBCL.
Eastern Cooperative Oncology Group (ECOG) performance status(P.S.) less than or equal to 2.
Age greater than or equal to 18 years.
Human immunodeficiency virus (HIV) serology negative
Phase I portion consists of 3-4 dose levels of 3-6 patients each.
Administer weekly times 4 and then 2 weeks off (1 cycle). Restage after every 2 cycles.
Continue if complete response (CR), partial response (PR) or stable disease (SD) for up to 6
cycles. Dose reductions for toxicity will be addressed in the protocol.
Phase II portion of the study will be a Simon optimal two-stage design: designed to rule out
20% response rate (p0=0.20) in favor of a 45% response rate (p1=0.45).
The maximum sample size to be accrued for this study will be 71 patients.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants With Adverse Events (e.g. Toxicity)
Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Kieron M Dunleavy, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|