Flavopiridol in Treating Patients With Refractory or Recurrent Mantle Cell Lymphoma or Diffuse Large B-Cell Lymphoma - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00445341

Purpose

RATIONALE: Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I/II trial is studying the side effects and best dose of flavopiridol and to see how well it works in treating patients with refractory or recurrent mantle cell lymphoma or diffuse large B-cell lymphoma.

Condition	Intervention	Phase
Lymphoma	Drug: alvocidib Genetic: microarray analysis Genetic: proteomic profiling Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: pharmacological study	Phase I Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Alvocidib Flavopiridol

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase I/II Study of Flavopiridol in Relapsed or Refractory Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma (DLBCL)

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose (Phase I) [ Designated as safety issue: Yes ]
Toxicity (Phase I) [ Designated as safety issue: Yes ]
Response rate (complete response and partial response) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacokinetics [ Designated as safety issue: No ]
Incidence of tumor lysis syndrome [ Designated as safety issue: No ]

Estimated Enrollment:	71
Study Start Date:	February 2007
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Assess the response of patients with refractory or recurrent mantle cell lymphoma or diffuse large B-cell lymphoma treated with flavopiridol.
Assess the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of this drug in these patients.

Secondary

Determine the pharmacokinetics of this drug in these patients.
Correlate pharmacokinetics with toxicity and the incidence of tumor lysis syndrome.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II, open-label study. Patients enrolled in the phase II portion of the study are stratified according to disease (mantle cell lymphoma vs diffuse large B-cell lymphoma).

Phase I: Patients receive flavopiridol IV over 4½ 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 receive flavopiridol as in phase I at the MTD determined in phase I.

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). Samples are also analyzed for expression of Ki67 and by TUNEL staining.

After completion of study treatment, patients are followed every 3-4 months until disease progression and then periodically thereafter.

PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Pathologically confirmed refractory or recurrent mantle cell lymphoma OR diffuse large B-cell lymphoma (DLBCL), 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
Measurable disease, defined as one of the following:
- Measurable disease in 2 dimensions
- Leukemic disease that can be quantified and followed
Prior anthracycline-based treatment required for patients with DLBCL
No active CNS lymphoma

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Absolute neutrophil count > 1,000/mm³ (independent of transfusions)
Platelet count > 50,000/mm³ (independent of transfusions)
WBC ≤ 100,000/mm³
Creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min
ALT < 5 times upper limit of normal
Bilirubin < 2 mg/dL (< 5 mg/dL in patients with Gilbert's syndrome, defined as > 80% unconjugated bilirubin)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No HIV positivity
Hepatitis B surface antigen negative
No history of inflammatory bowel disease (unless inactive for ≥ 2 years)

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from all prior therapy
More than 4 weeks since prior systemic cytotoxic therapy
More than 4 weeks since prior experimental treatments

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00445341

Locations

United States, Maryland
NCI - Center for Cancer Research	Recruiting
Bethesda, Maryland, United States, 20892
Contact: Clinical Trials Office - NCI - Center for Cancer Research 888-624-1937
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Kieron Dunleavy, MD

NCI - Metabolism Branch;MET

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Web site for additional information This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	NCI - Metabolism Branch;MET ( Kieron Dunleavy )
Study ID Numbers:	CDR0000532812, NCI-07-C-0081, NCI-P7040
Study First Received:	March 7, 2007
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00445341 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent mantle cell lymphoma
recurrent adult diffuse large cell lymphoma

Study placed in the following topic categories:

Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Protein Kinase Inhibitors
Recurrence
Lymphoma, B-Cell

Lymphatic Diseases
Flavopiridol
B-cell Lymphomas
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma, Large-cell
Lymphoma

Additional relevant MeSH terms:

Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Immunoproliferative Disorders
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Growth Substances
Lymphoma, Mantle-Cell
Physiological Effects of Drugs
Enzyme Inhibitors
Protein Kinase Inhibitors

Pharmacologic Actions
Lymphoma, B-Cell
Lymphatic Diseases
Flavopiridol
Neoplasms
Therapeutic Uses
Growth Inhibitors
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma

ClinicalTrials.gov processed this record on May 06, 2009