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

December 22, 2014 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

93

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
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.
Other: Pharmacological Study
Correlative studies
Other Names:
  • pharmacological studies
Drug: Alvocidib Hydrochloride
Given IV
Other Names:
  • FLAVO
  • HMR 1275
  • HL-275
Drug: Bortezomib
Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Recommended phase II dose
Time Frame: 21 days
21 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose, assessed according to NCI CTCAE v4.0
Time Frame: 21 days
21 days
Response
Time Frame: Up to 8 years
Up to 8 years
Response duration
Time Frame: Up to 8 years
Up to 8 years
Time to progression
Time Frame: Up to 8 years
Up to 8 years
Survival
Time Frame: Up to 8 years
Up to 8 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Steven Grant, Moffitt Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2004

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

May 14, 2004

First Submitted That Met QC Criteria

May 18, 2004

First Posted (Estimate)

May 19, 2004

Study Record Updates

Last Update Posted (Estimate)

December 23, 2014

Last Update Submitted That Met QC Criteria

December 22, 2014

Last Verified

October 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00058 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • P30CA076292 (U.S. NIH Grant/Contract)
  • N01CM00100 (U.S. NIH Grant/Contract)
  • CDR0000360816
  • MCC 6413
  • MCC-6413 (Other Identifier: Moffitt Cancer Center)
  • 6413 (CTEP)
  • R21CA110953 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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