A Pilot Study of Standard-Dose Rituximab, Ifosfamide, Carboplatin and Etoposide (RICE) Plus Bortezomib (Velcade) in a Dose-Escalating Fashion for Patients With Relapsed or Primary Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma Who Are Candidates for Autologous Stem Cell Transplant

University of California San Francisco (UCSF)

Status and phase

Terminated

Early Phase 1

Conditions

Lymphoma, B-Cell

Treatments

Drug: Rituximab, Ifosfamide, Carboplatin, Etoposide, Bortezomib

Study type

Interventional

Funder types

Other

Identifiers

NCT00515138

UC-CC06253

Details and patient eligibility

About

This study seeks to determine the maximum tolerated dose of bortezomib in combination with rituximab, ifosfamide, carboplatin, and etoposide for patients with relapsed or primary refractory aggressive B-Cell Non-Hodgkin's lymphoma (diffuse large B-cell, mantle cell, follicular grade III, transformed lymphoma). Subjects will be enrolled in cohorts of 3 at each bortezomib dose level, starting at 1 mg/m(2), and escalating to 1.3, 1.5, and 1.7 mg/m(2). Bortezomib will be given on days 1 (prior to rituximab) and 4, rituximab 375 mg/m(2)/day on days 2, 3, and 4 of a 21-day cycle. They will also receive filgrastim on days 6-13 or pegfilgrastim on day 6.

Enrollment

7 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Aggressive B-Cell Lymphoma, CD-20 positive, in first relapse or refractory to first-line chemotherapy
- Diffuse large B-cell Lymphoma, Mantle cell lymphoma, Follicular lymphoma (Grade III), Transformed Follicular Lymphoma
- Rituximab is allowed
- Prior radiation is allowed
18-70 years of age
ECOG performance status of 0-2
HIV seronegative
Measurable disease on CT scan by international working group response criteria
No CNS involvement
Subject is considered to be a candidate for autologous stem cell transplant in the opinion of the treating physician
Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control
Male subject agrees to use an acceptable method of contraception for the duration of the study

Exclusion criteria

Platelet count of <75 x 10(9)/L
Absolute neutrophil count of <1.0 x 10(9)/L
Calculated or measured creatinine clearance of <60 mL/minute within 14 days before enrollment
Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
Subject has hypersensitivity to bortezomib, boron or mannitol.
Female subject is pregnant or breast-feeding.
Subject has been treated with more than one prior chemotherapy regimen.
Subject has received other investigational drugs with 14 days before enrollment.
Serious medical or psychiatric illness likely to interfere with participation in this clinical study.