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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Nodal Marginal Zone 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 Plasma Cell Myeloma, Splenic Marginal Zone Lymphoma, Waldenstrom Macroglobulinemia

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Alvocidib Hydrochloride
* Other: Pharmacological Study


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>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<br>* Given IV<br>Drug: Alvocidib Hydrochloride<br>* Given IV<br>* Other names: HMR 1275;Other: Pharmacological Study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended phase II dose |  | 21 days | 

Secondary Outcome Measures

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