Conditions: Non-hodgkin's Lymphoma Mantle Cell Lymphoma
Keywords: non-hodgkin's lymphoma mantle cell lymphoma BEAM Velcade
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 42
Healthy volunteers: no

Brief summary:
This is a Phase I/II trial designed to study the toxicity and Maximum Tolerated Dose (MTD) of bortezomib in combination with BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT) and to obtain a preliminary estimate of the response rate to this combination.

Detailed description:
Primary Objective:The primary objective of the study is to evaluate the toxicity and determine the maximum tolerated dose (MTD) of bortezomib when added to a standard BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) conditioning regimen followed by autologous hematopoietic stem cell transplantation (ASCT).

Secondary Objective: The secondary objective of the study is to obtain a preliminary estimate of the overall response rate (ORR), progression free survival (PFS), and overall survival (OS) with this regimen.

Enrolled subjects will receive bortezomib in combination with BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (AHSCT). Phase I treatment will administer bortezomib in four dose cohorts,in addition to the BEAM and ASCT. 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 bortezomib 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 overall response rate, progressions free survival and overall survival using this regimen.

Arms:
arm 1: The phase I section of the study will follow a standard 3 + 3 design to determine the maximum tolerated dose (MTD) of bortezomib when added to a standard BEAM (BCNU (carmustine), etoposide, cytarabine, melphalan) conditioning regimen followed by autologous hematopoietic stem cell transplantation (ASCT).

After the MTD is defined, additional patients will enroll in Phase II to obtain preliminary estimates of survival using the Phase I regimen.

Interventions: intervention 1: Bortezomib intervention 2: BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan)
Intervention descriptions: intervention 1: Patients will receive bortezomib in four dose cohorts ( .8. 1.0, 1.3, 1.5 mg/m²). Patients will receive bortezomib on days -11, -8, -5, and -2 before infusion of autologous stem cells. intervention 2: All study patients will receive BEAM per the standard institution protocol:

BCNU (carmustine): 300 mg/m²on day -5 etoposide 100 mg/m² twice daily on days -5, -4, -3, and -2 cytarabine 100 mg/m² twice daily on days -5, -4, -3, -2 melphalan: 140 mg/m² on day -1 before infusion of autologous stem cells.

Protocol document: