Questions About Cancer? 1-800-4-CANCER
  • Print
  • Email
  • Facebook
  • Twitter
  • Google+
  • Pinterest

Treating Relapsed or Refractory B-cell Lymphomas

Name of the Trial

Phase I/II Study of Flavopiridol in Patients with Refractory or Recurrent Mantle Cell Lymphoma or Diffuse Large B-Cell Lymphoma (NCI-07-C-0081). See the protocol summary.

Principal Investigator

Dr. Kieron Dunleavy, NCI Center for Cancer Research

Dr. Kieron Dunleavy
Dr. Kieron Dunleavy
Principal Investigator

Why This Trial Is Important

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), accounting for up to 30 percent of new cases. DLBCL is an aggressive lymphoma, and, although many patients can be cured with current therapies, the prognosis for patients with relapsed DLBCL is often poor. Mantle cell lymphoma (MCL) is a less-common type of NHL; however, it is usually not curable with current therapies. New treatment options are needed for patients with relapsed or treatment-resistant (refractory) DLBCL or MCL.

Scientists are studying the drug flavopiridol to see if it can be effective in treating these diseases. Flavopiridol belongs to a class of drugs known as cyclin-dependent kinase (CDK) inhibitors. CDKs are proteins that help control cell proliferation. To be active, CDKs must interact with other proteins called cyclins.

MCL cells are distinguished by an excess of cyclin D1, and scientists believe that blocking the activity of this protein through CDK inhibition is a potential therapeutic strategy that may cause MCL cells to die. In addition, preliminary results suggest that flavopiridol may be active against DLBCL.

"Because there are numerous molecular targets for this drug in these diseases, we have a very good scientific rationale for investigating flavopiridol in these lymphomas," said Dr. Dunleavy. "We hope that inhibiting these targets with flavopiridol will cause these tumor cells to undergo apoptosis, or programmed cell death."

Although a different administration schedule of flavopiridol has been tested previously in the treatment of MCL with disappointing results, Dr. Dunleavy noted that this trial is employing a novel method of drug delivery that incorporates both continuous infusion over several hours and a bolus infusion that delivers a large initial pulse of drug.

"Originally developed for and tested in patients with chronic lymphocytic leukemia, where it showed excellent efficacy, this hybrid schedule of administration aims to achieve levels of flavopiridol that can effectively kill lymphoma cells," Dr. Dunleavy said.

For More Information

See the list of eligibility criteria and contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

  • Posted: July 22, 2008