Flavopiridol to Treat Relapsed Mantle Cell Lymphoma or Diffuse Large B-Cell Lymphoma

NCT00445341 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 07008107-C-0081
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) are aggressive subtypes of non-Hodgkin lymphoma. Flavopiridol is an investigational drug that works differently from standard chemotherapy and may target abnormalities in MCL and DLBCL cells, such as a protein excess that prevents tumor cells from dying. A challenge in developing flavopiridol for treatment has been determining its optimal dosing schedule. The schedule used for this study is effective in a type of leukemia called chronic lymphocytic leukemia (CLL) and may benefit patients with MCL and DLBCL also. Objectives: To determine the highest dose of flavopiridol that can be given safely to patients with relapsed MCL and DLBCL at the dosing schedule detailed below To assess the response of the tumor to flavopiridol given at the test dosing schedule Eligibility: Patients 18 years of age and older with relapsed MCL or DLBCL Design: Flavopiridol is given at four different dose levels, starting with the lowest dose for the first group of three to six patients and increasing with subsequent groups, depending on side effects at the preceding dose. The drug is given weekly for 4 weeks followed by a 2-week break (one cycle) for up to six cycles. It is given through a vein as a 30-minute infusion followed by a 4-hour infusion. Patients undergo the following procedures for research studies and to evaluate the effect of treatment on the tumor:

• Blood tests
• Lymph node, bone marrow and tumor biopsies
• Lymphapheresis to collect blood cells for research
• Disease staging with imaging studies (computed tomography (CT), positron emission tomography (PET) and/or magnetic resonance imaging (MRI) after every 2 cycles

Conditions

Lymphoma

Keywords

Microarray; Proteomics; Hybrid Schedule; Tumor Lysis Syndrome; Cyclin D1; Lymphoma; Mantle Cell Lymphoma; MCL; Diffuse Large B-Cell Lymphoma; DLBCL

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events (e.g. Toxicity)

  Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

  47 months

• Response Rate (Complete Response (CR) and Partial Response (PR))

  Response was assessed by the Cheson criteria. Complete response is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g.(LDH) definitely assignable to the lymphoma. All lymph nodes must have regressed to normal size (\</= 1.5 cm in greatest diameter if \> 1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in greatest diameter must have decreased to \</= 1 cm or by more than 75% in the sum of the products of the greatest diameters (SPD). Spleen, if considered to be enlarged before therapy, must have regressed in size. Partial response is a \>/= 50% decrease in the SPD of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Splenic and hepatic nodules must regress by \>/= 50% in the SPD. Bone marrow is irrelevant for determination of a PR.

  2/16/2007 - 1/20/2011

Study Arms (1)

Flavopiridol in lymphoma patients

EXPERIMENTAL

Flavopiridol 30 mg/m\^2 is given weekly for 4 weeks followed by a 2 week break for up to 6 cycles. It is given through a vein as a 30 minute infusion followed by a 4 hour infusion.

Drug: Flavopiridol

Interventions

Flavopiridol DRUG

Flavopiridol 30 mg/m\^2 is given weekly for 4 weeks followed by a 2 week break for up to 6 cycles. It is given through a vein as a 30 minute infusion followed by a 4 hour infusion.

Also known as: alvocidib

Flavopiridol in lymphoma patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Pregnant or nursing because of an unknown potential for teratogenic or abortifacient effects.
• Human immunodeficiency virus (HIV) serology negative. HIV positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with flavopiridol. Additionally, the biology of HIV associated DLBCL's is often quite different from HIV negative disease due to involvement of Epstein Barr virus (EBV).
• Hepatitis B surface antigen negative.
• Active central nervous system (CNS) lymphoma. These patients have a poor prognosis and because they frequently develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse events.
• History of inflammatory bowel disease unless this has been inactive for a period of 2 or more years.
• Recovery from toxicity of prior therapy to a grade 1 or less.
• Systemic cytotoxic or experimental treatments within 4 weeks of treatment.
• White blood cell (WBC) greater than 100,000 cells/mcL.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Worland PJ, Kaur G, Stetler-Stevenson M, Sebers S, Sartor O, Sausville EA. Alteration of the phosphorylation state of p34cdc2 kinase by the flavone L86-8275 in breast carcinoma cells. Correlation with decreased H1 kinase activity. Biochem Pharmacol. 1993 Nov 17;46(10):1831-40. doi: 10.1016/0006-2952(93)90590-s.

  PMID: 8250970 BACKGROUND

• Arguello F, Alexander M, Sterry JA, Tudor G, Smith EM, Kalavar NT, Greene JF Jr, Koss W, Morgan CD, Stinson SF, Siford TJ, Alvord WG, Klabansky RL, Sausville EA. Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity In vivo against human leukemia and lymphoma xenografts. Blood. 1998 Apr 1;91(7):2482-90.

  PMID: 9516149 BACKGROUND

• Byrd JC, Peterson BL, Gabrilove J, Odenike OM, Grever MR, Rai K, Larson RA; Cancer and Leukemia Group B. Treatment of relapsed chronic lymphocytic leukemia by 72-hour continuous infusion or 1-hour bolus infusion of flavopiridol: results from Cancer and Leukemia Group B study 19805. Clin Cancer Res. 2005 Jun 1;11(11):4176-81. doi: 10.1158/1078-0432.CCR-04-2276.

  PMID: 15930354 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphoma; Tumor Lysis Syndrome; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse

Interventions

alvocidib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Results Point of Contact

• Title: Kieron Dunleavy, M.D.
• Organization: National Cancer Institute, National Institutes of Health

DunleavK@mail.nih.gov

301-435-1007

Study Officials

• Mark Roschewski, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 7, 2007
• First Posted: March 9, 2007
• Study Start: November 27, 2006
• Primary Completion: April 30, 2012
• Study Completion: October 18, 2012
• Last Updated: January 30, 2018
• Results First Posted: October 5, 2012

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)