This is a Phase I/II trial designed to study the toxicity and Maximum Tolerated Dose of
VELCADE in combination with BEAM and autologous hematopoietic stem cell transplantation and
to obtain a preliminary estimate of the response rate to this combination.
Primary Objective: To evaluate in a phase I study the toxicity and MTD of the addition of
VELCADE™ (bortezomib) to a standard BEAM autologous transplant regimen. The phase II
portion of the study will determine a preliminary estimate of the response rate.
Secondary Objectives: To obtain a preliminary estimate of the response rate to this regimen.
To obtain preliminary estimates of event-free and overall survival using this regimen.
Enrolled subjects will receive Velcade in combination with BEAM and Autologous Hematopoietic
Stem Cell Transplantation (AHSCT). Phase I treatment will administer Velcade in four dose
cohorts,in addition to the BEAM and AHSCT. Three patients will be accrued in each dose
cohort with enrollment starting at dose cohort. These subjects will be evaluated to
establish the maximum tolerated dose of Velcade in combination with BEAM autologous
peripheral blood stem cell transplantation. Once established, the maximum tolerated dose
will be utilized in treating an additional 20 subjects.
Follow-Up: Data collected will be utilized to obtain a preliminary estimate of the response
rate, event-free and overall survival using this regimen.
- Persistent, relapsed or refractory indolent non-Hodgkin's lymphoma (Follicular grade
I, II, or III), non-Hodgkin's lymphoma, composite lymphomas with ≥ 50% of tumor
showing follicular histology, transformed follicular, lymphoplasmacytic, marginal
zone lymphoma, small Lymphocytic Lymphoma (including T-cell subtypes), or mantle cell
lymphoma that is relapsed, refractory, or in PR1 or CR1 (MCL only for CR1).
- Age >19 years.
- Signed written informed consent.
- Expected survival duration of > six months.
- Karnofsky Performance Status > 70.
- Eligible patients must have: Liver functions < 3x upper limits of normal (ULN)
unless due to disease; ANC > 500 cells/mm3 and Platelet Count > 50 mm3.
- Patients > age 60 or with clinical signs of heart disease must have ejection fraction
≥ 45% LVEF.
- Patients with clinical signs of pulmonary insufficiency must have DLCO to be measured
at > 50% of predicted value.
- Able to collect > 1.2 X 106/kg CD34+ cell for transplantation.
- No serious disease or condition that, in the opinion of the investigator, would
compromise the patient's ability to participate in the study.
- Female patients must not be pregnant or lactating.
- Male and female patients of reproductive potential must follow accepted birth control
- Patients who are HIV seropositive
- Serum creatinine >2.5mg/dL or calculated creatinine clearance ≤ 50ml/min
- Total bilirubin >3 times upper limits of normal (unless due to Gilberts disease or
malignancy), ALT and AST >4 times the upper limits of normal
- Active infection at the time of transplant
- Myocardial infarction within 6 months prior to enrollment or has New York Hospital
Association (NYHA) 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
- Patient has hypersensitivity to bortezomib, boron or mannitol.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not
pregnant must be established by a negative serum pregnancy test result obtained
during screening. Pregnancy testing is not required for post-menopausal or
surgically sterilized women.