Clinical trial NCT00082784: Bortezomib and Flavopiridol in Treating Patients With Recurrent or Refractory Indolent B-Cell Neoplasms
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-05-19
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Recommended phase II dose
timeFrame: 21 days
Secondary outcomes:
measure: Maximum tolerated dose, assessed according to NCI CTCAE v4.0
timeFrame: 21 days
measure: Response
timeFrame: Up to 8 years
measure: Response duration
timeFrame: Up to 8 years
measure: Time to progression
timeFrame: Up to 8 years
measure: Survival
timeFrame: Up to 8 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
Study officials:
affiliation: Moffitt Cancer Center
name: Steven Grant
role: PRINCIPAL_INVESTIGATOR
References: