Trial of VELCADE and Rituxan as Front-line Tx for Low-grade NHL

The primary objective of this study is to assess the overall response rate. Overall response rate at this time point will be defined as complete response \[CR\] plus partial response \[PR\]) after 3 cycles of bortezomib/rituximab induction therapy for patients with previously untreated low-grade, B-cell NHL. Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase \[LDH\]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present). Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.

Time frame: At baseline and at the completion of 3 cycles of treatment where 1 cycle equals 35 days.

Correlation of tumor burden according to Groupe D'Etude des Lymphomes Follicularies (GELF) with recently developed Follicular Lymphoma International Prognostic Index (FLIPI) prognostic index. All patients enrolled in the study were required to have high tumor burden (HTB) as defined by GELF, where HTB is defined as representing higher risk disease and poorer outcomes than low tumor burden (LTB). Patients were put into low risk or high risk FLIPI groups. Low risk group with a score of 0-2 and high risk group with a score of 3-5. A FLIPI score of 0 to 1 = low risk with a 10 year overall survival of 70%. A score of 2= intermediate risk with a 10 year overall survival of 50%. Finally, a score of ≥ 3 is considered high risk with a 10 year overall survival of 35%. Data was collected in connection with high or low risk FLIPI and Progression Free Survival (PFS) or Overall Survival (OS) and is reported as percentage patient with high/low risk that are progression free or alive.

Time frame: At the start of treatment and at Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, PFS and OS for all patients is reported at 4 years.

The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded)until the first date that recurrent or progressive disease is objectively documented. Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase \[LDH\]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present). Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen. Progressive disease (PD) requires the appearance of any new lesion or increase by \> 50% in the size of previously involved sites.

Time frame: Every 2 months for up to 12 months then every 6 months for 2 years and annually for 1 year

Population: Data was not collected or analyzed for duration of response.

Assess the safety and tolerance of bortezomib/rituximab as induction and maintenance therapy. Data will be collected for grade 3 and grade 4 adverse events experienced by patients that are determined to be at least possibly related to at least one study drug. Toxicity data for bortezomib/rituximab will be collected on day 1 of every cycle (1 cycle = 35 days) for up to 7 cycles during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Time frame: Day 1 of each cycle and at the completion of cycles 1 and 3, during treatment up to 12 months

Overall response rate (ORR) after 1 cycle of bortezomib/rituximab induction therapy. Overall response rate at this time point will be defined as complete response \[CR\] plus partial response \[PR\]) after 1 cycle of bortezomib/rituximab induction therapy for patients with previously untreated low-grade, B-cell NHL. Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase \[LDH\]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present). Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.

Time frame: At baseline and at the completion of cycle 1 (1 cycle =35 days)

Overall response rate at completion of bortezomib/rituximab maintenance therapy. Overall response rate at this time point will be defined as complete response \[CR\] plus partial response \[PR\]) after 3 cycles of bortezomib/rituximab induction therapy and up to 4 cycles of maintenance for patients with previously untreated low-grade, B-cell NHL. Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase \[LDH\]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present). Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.

Time frame: At baseline and every 2 months during treatment of up to 3 cycles of induction (1 cycle =35days) and 4 cycles of maintenance (1 cycle =2 months) for up to 12 months.

Time to Treatment Failure (TTF) rate measured, from the time of first treatment to disease progression, relapse, second tumor, death from any cause, treatment toxicity requiring termination from the study, or for any reason treatment is discontinued permanently.

Time frame: Median follow up for all patients was 50 months and on intent to treat, TTF rate for all patients is reported at 4 years.

Progression Free Survival is measured from the time of first induction infusion to disease progression, relapse, second tumor, or death from any cause. Progressive disease (PD) requires the following: 1. Appearance of any new lesion or increase by \> 50% in the size of previously involved sites. 2. Increase of \> 50% in the SPD from nadir measurement of all involved dominant lymph nodes and liver nodules and spleen nodules or unequivocal progression in any non measurable disease or nondominant site. 3. \> 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node

Time frame: Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, PFS for all patients is reported at 4 years.

Tissue microarray analysis from paraffin embedded tissue, gene expression profiling from frozen tissue (both from initial node biopsy collected/stored) and whole blood analysis of FCγR polymorphism

Time frame: At baseline and at response assessment 1 after induction part A, 2, after induction part B and 3, maintenance period.

Population: Insufficient tumor samples were submitted for insufficient number of patients. No data was collected or analyzed.

Overall survival (OS) will be measured from the time of first treatment to death from any cause.

Time frame: Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, OS rate for all patients is reported at 4 years.