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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Waldenstrom Macroglobulinemia; Nodal Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Refractory Plasma Cell Myeloma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue

Treatments: Drug: Alvocidib Hydrochloride; Drug: Bortezomib; Other: Pharmacological Study

Study type: Interventional

Funder types: NIH

Identifiers

NCT00082784

6413 (Other Identifier)

MCC-6413 (Other Identifier)

R21CA110953 (U.S. NIH Grant/Contract)

MCC 6413

P30CA076292 (U.S. NIH Grant/Contract)

CDR0000360816

NCI-2009-00058 (Registry Identifier)

N01CM00100 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 93 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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93 participants in 1 patient group

Treatment

Experimental group

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.

Treatment:

Other: Pharmacological Study

Drug: Bortezomib

Drug: Alvocidib Hydrochloride