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

Primary Purpose

Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Nodal Marginal Zone Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bortezomib
Alvocidib Hydrochloride
Pharmacological Study
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Moffitt Cancer Center
  • University of Pittsburgh Cancer Institute
  • University of Pittsburgh
  • Medical University of South Carolina
  • Virginia Commonwealth University/Massey Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

Recommended phase II dose

Secondary Outcome Measures

Maximum tolerated dose, assessed according to NCI CTCAE v4.0
Response
Response duration
Time to progression
Survival

Full Information

First Posted
May 14, 2004
Last Updated
December 22, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00082784
Brief Title
Bortezomib and Flavopiridol in Treating Patients With Recurrent or Refractory Indolent B-Cell Neoplasms
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
March 2004 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, 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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
93 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Alvocidib Hydrochloride
Other Intervention Name(s)
FLAVO, HL-275, HMR 1275
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Recommended phase II dose
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Maximum tolerated dose, assessed according to NCI CTCAE v4.0
Time Frame
21 days
Title
Response
Time Frame
Up to 8 years
Title
Response duration
Time Frame
Up to 8 years
Title
Time to progression
Time Frame
Up to 8 years
Title
Survival
Time Frame
Up to 8 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Grant
Organizational Affiliation
Moffitt Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

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

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