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 at http://cancer.gov/clinicaltrials/NCI-07-C-0081.

Principal Investigator
Dr. Kieron Dunleavy, NCI Center for Cancer Research

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 at http://cancer.gov/clinicaltrials/NCI-07-C-0081 or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

Source: NCI Cancer Bulletin. July 22, 2008

New Drugs for Multiple Myeloma Consolidation Therapy

Name of the Trial
Phase III Randomized Study of Consolidation Therapy Comprising Bortezomib and Dexamethasone with Versus without Lenalidomide in Patients with Symptomatic Multiple Myeloma Who Have Completed a Dexamethasone-Based Induction Regimen (ECOG-E1A05). See the protocol summary at http://cancer.gov/clinicaltrials/ECOG-E1A05.

Principal Investigator
Dr. Rafael Fonseca and Dr. S. Vincent Rajkumar, Eastern Cooperative Oncology Group

Why This Trial Is Important
Multiple myeloma is a type of cancer that begins in plasma cells, white blood cells that are part of the immune system. In this disease, malignant plasma cells (myeloma cells) multiply and form small lesions in the bone marrow and the solid parts of bone. Although multiple myeloma is usually not curable, advances in drug treatment and the use of stem cell transplantation have substantially increased the average survival time of patients with this disease.

Patients with multiple myeloma are often treated first with chemotherapy drugs and the steroid dexamethasone to induce remission (induction therapy). This is often followed by “consolidation therapy” with high-dose chemotherapy and stem cell transplantation. Although consolidation therapy has produced longer survival, the side effects associated with it can be severe and may dramatically affect quality of life. Doctors want to study new consolidation therapy options, using recently developed drugs, to see if they can achieve the same or better outcomes without as much risk to the patient.

In this trial, newly diagnosed patients who have undergone induction therapy will be treated with consolidation therapy consisting of dexamethasone and the drug bortezomib. Some patients will also be randomly assigned to receive a third drug called lenalidomide. Both bortezomib and lenalidomide have been approved by the FDA to treat patients with relapsed multiple myeloma, and they have shown promise in early clinical trials involving patients with newly diagnosed disease.

“One of the biggest questions in the minds of patients in this era of new drugs is, ‘Do we still need to have a transplant?’” said Dr. Rajkumar. “Autologous transplants are associated with significant morbidity and can be life changing. Both of these regimens hold the promise of high response rates that may rival what we can achieve with stem cell transplantation while being easier on patients.”

For More Information
See the list of entry criteria and trial contact information at http://cancer.gov/clinicaltrials/ECOG-E1A05 or call the NCI Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

Source: NCI Cancer Bulletin. July 8, 2008