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

Phase 1

Completed

• Conditions: Refractory Plasma Cell Myeloma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma
• Interventions: Drug: Bortezomib; Drug: Alvocidib Hydrochloride; Other: Pharmacological Study

• Registration Number: NCT00082784
• Lead Sponsor: National Cancer Institute (NCI)

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.

Study Timeline

• Study Start: 2004-03
• Study First Submitted: 2004-05-14
• Study First Submitted QC: 2004-05-18
• Study First Posted: 2004-05-19
• Primary Completion: 2012-10
• Study Completion: 2014-09
• Status Verified: 2014-10
• Last Update Submitted: 2014-12-22
• Last Update Posted: 2014-12-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 93

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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Bortezomib	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.
Treatment	Alvocidib Hydrochloride	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.
Treatment	Pharmacological 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.

Primary Outcome Measures

Name	Time	Method
Recommended phase II dose	21 days

Secondary Outcome Measures

Name	Time	Method
Survival	Up to 8 years
Response	Up to 8 years
Response duration	Up to 8 years
Time to progression	Up to 8 years
Maximum tolerated dose, assessed according to NCI CTCAE v4.0	21 days

Trial Locations

Locations (5)

University of Pittsburgh Cancer Institute; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Virginia Commonwealth University/Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States