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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00082784
First received: May 14, 2004
Last updated: June 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell 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 Multiple Myeloma
Splenic Marginal Zone Lymphoma
Waldenström Macroglobulinemia
Drug: bortezomib
Drug: alvocidib
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Recommended phase II dose [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Maximum tolerated dose, assessed according to NCI CTCAE v4.0 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • Response [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Response duration [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: March 2004
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: alvocidib
Given IV
Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00082784

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Grant H. Lee Moffitt Cancer Center and Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00082784     History of Changes
Other Study ID Numbers: NCI-2009-00058, NCI-2009-00058, CDR0000360816, MCC 6413, MCC-6413, 6413, P30CA076292, N01CM00100, R21CA110953
Study First Received: May 14, 2004
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Waldenstrom Macroglobulinemia
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Flavopiridol
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Growth Inhibitors
Growth Substances

ClinicalTrials.gov processed this record on July 10, 2014