Flavopiridol to Treat Relapsed Mantle Cell Lymphoma or Diffuse Large B-Cell Lymphoma

Phase 1

Completed

Conditions: Lymphoma

Interventions: Drug: Flavopiridol

Registration Number: NCT00445341

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

Mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) are aggressive subtypes of non-Hodgkin lymphoma.

Flavopiridol is an investigational drug that works differently from standard chemotherapy and may target abnormalities in MCL and DLBCL cells, such as a protein excess that prevents tumor cells from dying.

A challenge in developing flavopiridol for treatment has been determining its optimal dosing schedule. The schedule used for this study is effective in a type of leukemia called chronic lymphocytic leukemia (CLL) and may benefit patients with MCL and DLBCL also.

Objectives:

To determine the highest dose of flavopiridol that can be given safely to patients with relapsed MCL and DLBCL at the dosing schedule detailed below

To assess the response of the tumor to flavopiridol given at the test dosing schedule

Eligibility:

Patients 18 years of age and older with relapsed MCL or DLBCL

Design:

Flavopiridol is given at four different dose levels, starting with the lowest dose for the first group of three to six patients and increasing with subsequent groups, depending on side effects at the preceding dose. The drug is given weekly for 4 weeks followed by a 2-week break (one cycle) for up to six cycles. It is given through a vein as a 30-minute infusion followed by a 4-hour infusion.

Patients undergo the following procedures for research studies and to evaluate the effect of treatment on the tumor:

* Blood tests

* Lymph node, bone marrow and tumor biopsies

* Lymphapheresis to collect blood cells for research

* Disease staging with imaging studies (computed tomography (CT), positron emission tomography (PET) and/or magnetic resonance imaging (MRI) after every 2 cycles

Detailed Description: Background:

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).

Objectives:

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).

Eligibility:

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

Design:

Phase I/II.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Flavopiridol in lymphoma patients	Flavopiridol	Flavopiridol 30 mg/m\^2 is given weekly for 4 weeks followed by a 2 week break for up to 6 cycles. It is given through a vein as a 30 minute infusion followed by a 4 hour infusion.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (e.g. Toxicity)	47 months	Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Response Rate (Complete Response (CR) and Partial Response (PR))	2/16/2007 - 1/20/2011	Response was assessed by the Cheson criteria. Complete response is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g.(LDH) definitely assignable to the lymphoma. All lymph nodes must have regressed to normal size (\</= 1.5 cm in greatest diameter if \> 1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in greatest diameter must have decreased to \</= 1 cm or by more than 75% in the sum of the products of the greatest diameters (SPD). Spleen, if considered to be enlarged before therapy, must have regressed in size. Partial response is a \>/= 50% decrease in the SPD of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Splenic and hepatic nodules must regress by \>/= 50% in the SPD. Bone marrow is irrelevant for determination of a PR.

Secondary Outcome Measures