Non-Hodgkin's Lymphoma
Conditions
Keywords
diffuse large B cell, mantle cell lymphoma
Brief summary
Primary Objective: To determine the toxicity profile and maximum tolerated dose (MTD) of VELCADE when administered in combination with CHOP + Rituximab to patients with previously untreated diffuse large B cell or mantle cell non-Hodgkin's lymphoma (NHL) Secondary Objectives: To assess the response rate (overall and complete), event-free survival and overall survival with VELCADE and CHOP-R in patients with previously untreated diffuse large B cell or mantle cell lymphoma (phase II component) Treatment: Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the following dose escalation schedule: Level Dose/Schedule (-2) 0.7 mg/m2 on day 1 of each cycle (-1) 0.7 mg/m2 on days 1 and 8 (0) 0.7 mg/m2 on days 1 and 4 (+1) 1.0 mg/m2 on days 1 and 4 (+2) 1.3 mg/m2 on days 1 and 4
Detailed description
Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the following dose escalation schedule: Once completed six cycles of therapy (\ 18 weeks), patients will be evaluated every 3 months for the first year post treatment, then every 6 months until disease progression or death for years 2 through 5 post treatment. Patients who have disease progression will be contacted every 6 months until death to assess for survival status.
Interventions
DRUGBortezomib, CHOP, Rituximab
Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE (Bortezomib) is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the following dose escalation schedule: Level Dose/Schedule (-2) 0.7 mg/m2 on day 1 of each cycle (-1) 0.7 mg/m2 on days 1 and 8 (0) 0.7 mg/m2 on days 1 and 4 (+1) 1.0 mg/m2 on days 1 and 4 (+2) 1.3 mg/m2 on days 1 and 4
Sponsors
Millennium Pharmaceuticals, Inc.
Weill Medical College of Cornell University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the dose escalation schedule.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of diffuse large B cell or mantle cell Non-Hodgkin's Lymphoma with characteristic immunophenotypic profiles. For mantle cell: CD5(+), CD19(+) or CD20(+), cyclin D1(+), CD23(-) and CD10(-). * Patient has not received any prior anti-cancer therapy for lymphoma * Tumor tissue confirmed to express the CD20 antigen * Available frozen tumor tissue(rebiopsy if needed) * Patient has measurable disease as defined by a tumor mass \> 1.5 cm * Patient has Stage II, III, or IV disease * Age \> 18 years * Absolute granulocyte count \> 1000 cells/mm3 * Platelet count \> 50,000 cells/mm3 * Creatinine \< 2.0 x ULN * Total bilirubin \< 2.0 x ULN
Exclusion criteria
* Known central nervous system (CNS) involvement by lymphoma * Known HIV disease * Patient is pregnant or nursing * Patient has had major surgery within the last 3 weeks * Patient is receiving other investigational drugs * Known peripheral neuropathy \> Grade 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 6 cycles (18 weeks) | Overall Response Rate |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Untreated DLBCL with untreated Diffuse Large B-cell Lymphoma (n = 40) | 40 |
| Untreated MCL with untreated mantle cell Non-Hodgkin's Lymphoma | 36 |
| Total | 76 |
Baseline characteristics
| Characteristic | Untreated DLBCL | Untreated MCL | Total |
|---|---|---|---|
| Age, Continuous | 56 years | 66 years | 63 years |
| Sex: Female, Male Female | 13 Participants | 6 Participants | 19 Participants |
| Sex: Female, Male Male | 27 Participants | 30 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 76 / 76 |
| serious Total, serious adverse events | 1 / 76 |
Outcome results
Primary
ORR
Overall Response Rate
Time frame: 6 cycles (18 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Untreated DLBCL | ORR | 88 percentage of patients |
| Untreated MCL | ORR | 81 percentage of patients |