Clinical Trial for Lymphoma: 07-C-0081: 1.888.NCI.1937

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

Protocol # 07-C-0081

Why is this trial important?
Who is eligible for this trial?
What types of drugs or therapies are being used?
What is the study outline?
What is the frequency and duration of the visits?
What are the costs?
Who is the Principal Investigator?
Where is this trial taking place?
Who are the contacts for this trial?
Where can additional information be found?

Why is this trial important?

Flavopiridol is a novel drug that targets a number of different cellular pathways and processes. In the laboratory, it has been shown to be very effective against mantle cell lymphoma and diffuse large B-cell lymphoma cell lines. It is very effective against a number of targets in these lymphomas that are thought to be important in preventing "apoptosis" or programmed tumor cell death. One of the great challenges in developing flavopiridol has been optimizing its schedule and administration. Recently, a novel schedule of administration, comprising both bolus and continuous infusion delivery of the drug, has been developed and tried in patients with CLL where it has shown very promising results. We are testing this same schedule in patients with mantle cell and diffuse large B-cell lymphoma and hope that it will be an effective therapy in these groups.

Who is eligible for this trial? (PDQ)

Pathologically confirmed mantle cell lymphoma or diffuse large B-cell lymphoma, including any of the following:

Mediastinal (thymic) large B-cell lymphoma
Transformed large B-cell lymphoma
Follicular grade IIIB large B-cell lymphoma
Intravascular large B-cell lymphoma

Previously treated disease; recovered from all prior therapy
Prior anthracycline-based treatment for patients with DLBCL
Recurrent measurable disease
Age > 18 years
No active CNS lymphoma
HIV serology negative
Hepatitis B surface antigen negative
ECOG Performance Status 0-2
WBC ≤ 100,000/mm³
Absolute neutrophil count > 1,000/mm³ (independent of transfusions)
Platelet count > 50,000/mm³ (independent of transfusions)
Creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min
ALT < 5 times upper limit of normal (ULN)
Bilirubin < 2 mg/dL (< 5 mg/dL in patients with Gilbert's syndrome defined as > 80% unconjugated)
No history of inflammatory bowel disease (unless inactive ≥ 2 years)
Not pregnant or nursing

What types of drugs or therapies are being used?

Flavopiridol is the only drug that will be administered. Patients will receive prophylactic and other drugs as indicated.

What is the study outline? (PDQ)

This is a Phase I dose-escalation study followed by a Phase II portion.

Phase I

Patients receive flavopiridol IV over 4.5 hours once a week for 4 weeks
Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined
The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity

Phase II

Patients are stratified according to disease (mantle cell lymphoma vs. diffuse large B-cell lymphoma)
Patients receive flavopiridol at the MTD determined in Phase I
Patients receive flavopiridol IV over 4.5 hours once a week for 4 weeks
Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity
Blood samples are collected periodically for pharmacokinetic analysis and research studies (including microarray analysis, proteomic analysis, and immunohistochemistry of markers such as BCL-2, p53, MUM-1, BCL-6, MIB-1, and CD10)
After completion of study treatment, patients are followed every 3-4 months until disease progression and then periodically thereafter

What is the frequency and duration of the visits?

Patients are given flavopiridol once a week for 4 weeks followed by two weeks off. This 6-week period is one cycle. Patients are required to be admitted to the hospital the night before the first dose and stay for 24 hours after the first dose. If the first dose is tolerated well, then the next three doses may be given in the outpatient center. The second, third, and fourth doses require an 8- to 12-hour visit to the Clinical Center. During the two weeks between cycles, patients are required to have blood drawn once a week.

What are the costs?

There is no charge for medical care received at the National Institutes of Health (NIH) Clinical Center. Patients will be responsible for travel costs for their initial screening visits. In most cases, once patients are enrolled in a trial, the National Cancer Institute (NCI) will pay the transportation costs for all subsequent trial-related visits for patients who do not live in the local area. In addition, these patients will receive a small per diem to help offset the costs of meals and lodging if they are being treated as outpatients.

It will be important to maintain your current insurance plan to cover all medical care that is provided away from the NIH Clinical Center.

No U.S. citizen or permanent U.S. resident residing in the U.S. who otherwise meets the eligibility requirements will be denied enrollment in clinical research protocols because of their inability to pay the costs of travel and subsistence.

Who is the Principal Investigator?

Dr. Kieron Dunleavy was appointed Attending Staff Clinician at NCI in March 2006. He graduated from University College Dublin Medical School in 1994 and completed his residency and fellowship training at the Mater and St. James's Hospitals, Dublin, before coming to NCI in 2002 for a fellowship in Medical Oncology. Having completed his fellowship in February 2006, he was appointed to the position of Investigator/Attending Physician with the Metabolism Branch.

Dr. Dunleavy has authored and helped translate from bench to bedside several clinical trials. He plans to continue working as a clinical researcher, focusing on lymphoid malignancies. Dr. Dunleavy's goal is to continue to work in a collaborative capacity with the scientific community at NIH and apply novel discoveries and insights into the mechanisms and causes of lymphoid cancers in developing innovative therapies to combat these diseases.

Where is this trial taking place?

NIH Clinical Center
National Institutes of Health
NCI Medical Oncology Branch and Affiliates, Metabolism Branch
10 Center Drive
Bethesda, Maryland 20892

Who are the contacts for this trial?

Kieron Dunleavy, M.D.
Principal Investigator
Phone: 301-435-1007
dunleavk@mail.nih.gov

Wyndham H. Wilson, M.D., Ph.D.
Protocol Chair
Phone: 301-435-2415
wilsonw@mail.nih.gov

Referrals:

Therese White, R.N., M.S.N.
Research Nurse
Phone: 301-402-5886
whiteth@mail.nih.gov