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

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00082784
Collaborator
(none)
93
5
1
126
18.6
0.1

Study Details

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:
  1. To determine the recommended phase II dose of bortezomib and flavopiridol in patients with recurrent or refractory indolent B-cell neoplasms.
SECONDARY OBJECTIVES:
  1. To determine the toxic effects and maximum tolerated dose of this regimen in these patients.

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

  3. 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 Design

Study Type:
Interventional
Actual Enrollment :
93 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date :
Mar 1, 2004
Actual Primary Completion Date :
Oct 1, 2012
Actual Study Completion Date :
Sep 1, 2014

Arms and Interventions

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.

Drug: Bortezomib
Given IV

Drug: Alvocidib Hydrochloride
Given IV
Other Names:
  • FLAVO
  • HL-275
  • HMR 1275
  • Other: Pharmacological Study
    Correlative studies
    Other Names:
  • pharmacological studies
  • Outcome Measures

    Primary Outcome Measures

    1. Recommended phase II dose [21 days]

    Secondary Outcome Measures

    1. Maximum tolerated dose, assessed according to NCI CTCAE v4.0 [21 days]

    2. Response [Up to 8 years]

    3. Response duration [Up to 8 years]

    4. Time to progression [Up to 8 years]

    5. Survival [Up to 8 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Moffitt Cancer Center Tampa Florida United States 33612
    2 University of Pittsburgh Cancer Institute Pittsburgh Pennsylvania United States 15232
    3 University of Pittsburgh Pittsburgh Pennsylvania United States 15232
    4 Medical University of South Carolina Charleston South Carolina United States 29425
    5 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Steven Grant, Moffitt Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00082784
    Other Study ID Numbers:
    • NCI-2009-00058
    • NCI-2009-00058
    • CDR0000360816
    • MCC 6413
    • MCC-6413
    • 6413
    • R21CA110953
    • P30CA076292
    • N01CM00100
    First Posted:
    May 19, 2004
    Last Update Posted:
    Dec 23, 2014
    Last Verified:
    Oct 1, 2014

    Study Results

    No Results Posted as of Dec 23, 2014