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

OBJECTIVES:

Primary

- Determine the recommended phase II dose of bortezomib and flavopiridol in patients with
recurrent or refractory indolent B-cell neoplasms.

Secondary

- Determine the toxic effects and maximum tolerated dose of this regimen in these
patients.

- Determine disease-related effects of this regimen in these patients.

- Determine the pharmacodynamics of this regimen in patients with myeloma.

- 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.

Cohorts of 3-6 patients receive escalating doses of bortezomib and flavopiridol until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within 2½ years.

DISEASE CHARACTERISTICS:

- Diagnosis of one of the following:

- Follicle center lymphoma, follicular or diffuse

- Mantle cell lymphoma

- Marginal zone B-cell lymphoma, splenic, nodal, or extranodal

- Lymphoplasmacytoid lymphoma/immunocytoma

- Plasma cell myeloma

- Plasmacytoma

- Plasma cell leukemia

- Waldenstrom's macroglobulinemia

- Recurrent or refractory disease after at least 1 prior systemic treatment

- No prior CNS malignancy

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- 0-1

Life expectancy

- Not specified

Hematopoietic

- Hemoglobin ≥ 8 g/dL

- Platelet count ≥ 100,000/mm^3

- Absolute neutrophil count ≥ 1.5 x 10^9/L

Hepatic

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST/ALT ≤ 3 times ULN

Renal

- Calculated creatinine clearance ≥ 50 mL/min

Other

- 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 CONCURRENT THERAPY:

Biologic therapy

- Prior autologous stem cell transplantation allowed

- No prior allogeneic stem cell transplantation

Chemotherapy

- Not specified

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- Not specified

Other

- No other concurrent anticancer agents

- No other concurrent investigational agents