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A Phase I/II Study of Flavopiridol in Relapsed or Refractory Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma (DLBCL)

Phase 1/Phase 2
18 Years
Not Enrolling

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Trial Information

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/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.

Inclusion Criteria


Previously treated mantle cell lymphoma or diffuse large B-cell lymphoma (to include
mediastinal (thymic) large B-cell lymphoma; transformed large B-cell lymphoma; follicular
grade IIIB large B-cell lymphoma; intravascular large B-cell lymphoma).

Confirmed pathological diagnosis at the National Cancer Institute, National Institutes of
Health (NIH).

Recurrent measurable disease (measurable disease in 2 dimensions or leukemic disease which
can be quantified and followed).

Prior anthracycline-based treatment for patients with diffuse large B-cell lymphoma

Age greater than 18 years.

Eastern Cooperative Oncology Group (ECOG) performance 2 or better.

Major organ function: absolute neutrophil count (ANC) greater than 1000/mcL, Platelet
greater than 50,000/mcL, Creatinine less than 1.5 mg/dL or creatinine clearance greater
than 60 mL/min; serum glutamic pyruvic transaminase (SGPT) less than 5 x upper limit of
normal; bilirubin less than 2 mg/dL (total) except less than 5 mg/dL in patients with
Gilbert's syndrome as defined by greater than 80% unconjugated. ANC and platelet
requirements must be met independent of transfusion.

Informed consent and willingness to use contraception by both men and women.

Both male and female patients must be willing to use adequate contraception (to include
effective barrier methods of contraception) or to completely abstain from heterosexual
intercourse while on protocol treatment.


Pregnant or nursing because of an unknown potential for teratogenic or abortifacient

Human immunodeficiency virus (HIV) serology negative. HIV positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with flavopiridol. Additionally, the biology of HIV
associated DLBCL's is often quite different from HIV negative disease due to involvement
of Epstein Barr virus (EBV).

Hepatitis B surface antigen negative.

Active central nervous system (CNS) lymphoma. These patients have a poor prognosis and
because they frequently develop progressive neurological dysfunction that would confound
the evaluation of neurological and other adverse events.

History of inflammatory bowel disease unless this has been inactive for a period of 2 or
more years.

Recovery from toxicity of prior therapy to a grade 1 or less.

Systemic cytotoxic or experimental treatments within 4 weeks of treatment.

White blood cell (WBC) greater than 100,000 cells/mcL.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Adverse Events (e.g. Toxicity)

Outcome Description:

Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

Outcome Time Frame:

47 months

Safety Issue:


Principal Investigator

Kieron M Dunleavy, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

January 2007

Completion Date:

May 2012

Related Keywords:

  • Lymphoma
  • Microarray
  • Proteomics
  • Hybrid Schedule
  • Tumor Lysis Syndrome
  • Cyclin D1
  • Lymphoma
  • Mantle Cell Lymphoma
  • MCL
  • Diffuse Large B-Cell Lymphoma
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Mantle-Cell



National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892