Bortezomib and Flavopiridol in Treating Patients With Recurrent or Refractory Indolent B-Cell Neoplasms

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title:

Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol NSC 649890) in Patients With Recurrent or Refractory Indolent B-Cell Neoplasms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00082784
• Other study ID #: NCI-2009-00058
• Secondary ID: NCI-2009-00058CD
• Status: Completed
• Phase: Phase 1
• First received: May 14, 2004
• Last updated: December 22, 2014
• Start date: March 2004
• Est. completion date: September 2014

Study information

• Verified date: October 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop cancer cells from dividing so they stop growing or die. Bortezomib may increase the effectiveness of flavopiridol by making cancer cells more sensitive to the drug. Giving bortezomib together with flavopiridol may kill more cancer cells. This phase I trial is studying the side effects and best dose of bortezomib and flavopiridol in treating patients with recurrent or refractory indolent B-cell neoplasms.

Description:

PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose of bortezomib and flavopiridol in patients with recurrent or refractory indolent B-cell neoplasms.

SECONDARY OBJECTIVES:

I. To determine the toxic effects and maximum tolerated dose of this regimen in these patients.

II. To determine disease-related effects of this regimen in these patients. III. To determine the pharmacodynamics of this regimen in patients with myeloma.

IV. To determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive bortezomib IV over 3-5 seconds followed by flavopiridol IV over 1 hour on days 1, 4, 8, and 11.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: September 2014
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• WBC < 50,000/mm^3 for patients with circulating tumor cells

• No prior allergic reaction to compounds of similar chemical or biological composition to and presumably able to tolerated bortezomib, flavopiridol, allopurinol, sodium polystyrene sulfonate, or dexamethasone

• No neuropathy >= grade 2

• No other condition that would preclude study participation

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for 3 months after study participation

• Prior autologous stem cell transplantation is allowed

• No prior allogeneic stem cell transplantation

• No other concurrent anticancer agents

• No other concurrent investigational agents

• Hemoglobin >= 8 g/dL

• Platelet count >= 100,000/mm^3

• Absolute neutrophil count >= 1,500/mm^3

• Bilirubin =< 2 times upper limit of normal (ULN)

• AST/ALT =< 3 times ULN

• Creatinine =< 2 times ULN or Creatinine clearance >= 50 mL/min

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Nodal Marginal Zone Lymphoma
• Recurrent Adult Diffuse Large Cell Lymphoma
• Recurrent Adult Diffuse Mixed Cell Lymphoma
• Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
• Recurrent Grade 1 Follicular Lymphoma
• Recurrent Grade 2 Follicular Lymphoma
• Recurrent Grade 3 Follicular Lymphoma
• Recurrent Mantle Cell Lymphoma
• Recurrent Marginal Zone Lymphoma
• Refractory Plasma Cell Myeloma
• Splenic Marginal Zone Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

Drug:
• Bortezomib
Given IV
• Alvocidib Hydrochloride
Given IV

Other:
• Pharmacological Study
Correlative studies

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended phase II dose		21 days	Yes
Secondary	Maximum tolerated dose, assessed according to NCI CTCAE v4.0		21 days	Yes
Secondary	Response		Up to 8 years	No
Secondary	Response duration		Up to 8 years	No
Secondary	Time to progression		Up to 8 years	No
Secondary	Survival		Up to 8 years	No