Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Biomarker/Laboratory analysis, Treatment Active 18 and over NCI NCI-07-C-0081 NCI-P7040, 7844, NCT00445341

Special Category: NIH Clinical Center trial, NCI Web site featured trial

Objectives

Primary

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

Secondary

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

Entry 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

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

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)

Expected Enrollment

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

Outcomes

Maximum tolerated dose (Phase I)
Toxicity (Phase I)
Response rate (complete response and partial response)

Pharmacokinetics
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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Kieron Dunleavy, MD, Protocol chair		Ph: 301-435-1007

U.S.A.
Maryland
	Bethesda
	NCI - Center for Cancer Research
		Clinical Trials Office - NCI - Center for Cancer Research	Ph:  888-624-1937
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Related Information

Web site for additional information
Featured trial article

Registry Information
Official Title		A Phase I/II Study of Flavopiridol in Relapsed or Refractory Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma (DLBCL)
Trial Start Date		2007-02-01
Trial Completion Date		2009-11-17 (estimated)
Registered in ClinicalTrials.gov		NCT00445341
Date Submitted to PDQ		2007-01-19
Information Last Verified		2008-05-04