A Study of Rituximab Alternative Dosing Rate in Patients With Previously Untreated Diffuse Large B-cell or Follicular Non-Hodgkin's Lymphoma (RATE)
- Conditions
- Non-Hodgkin's Lymphoma
- Interventions
- Drug: CVP (cyclophosphamide, vincristine, prednisone)Drug: Analgesic/antipyretic and antihistamine drugs
- Registration Number
- NCT00719472
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This was a prospective, open-label, Phase III, multicenter, single-arm trial designed to assess the safety, pharmacokinetics, and pharmacodynamics of an alternative dosing rate of rituximab in previously untreated patients with diffuse large B-cell lymphoma (DLBCL) and follicular non-Hodgkin lymphoma (NHL).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 451
- Written informed consent
- Age ≥ 18 years
- Patients with previously untreated diffuse large B-cell lymphoma (DLBCL) who are scheduled to receive rituximab 375 mg/m^2 plus CHOP (cyclophosphamide, hydroxydaunorubicin [also called doxorubicin or adriamycin], Oncovin [vincristine], prednisone or prednisolone) chemotherapy, or previously untreated follicular non-Hodgkin lymphoma (NHL) who are scheduled to receive rituximab 375 mg/m^2 plus CVP (cyclophosphamide, vincristine, prednisolone) chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Clinically significant cardiovascular disease (eg, uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association (NYHA) Classification Grade II or greater congestive heart failure, a ventricular arrhythmia requiring medication within 1 year prior to Day 1, or NYHA Grade II or greater peripheral vascular disease on Day 1 (first day of treatment)
Patients who meet any of the following criteria will be excluded from further study participation after Cycle 1:
- Circulating lymphocyte count > 5,000/μL before the Cycle 2 rituximab infusion
- Development of a serious and/or Grade 3 or 4 adverse event during Cycle 1 judged by the investigator to be related to the rituximab infusion
- Prior premedication with additional corticosteroids other than the prednisone included in the chemotherapy regimens
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rituximab 375 mg/m^2 CVP (cyclophosphamide, vincristine, prednisone) Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle. Rituximab 375 mg/m^2 Analgesic/antipyretic and antihistamine drugs Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle. Rituximab 375 mg/m^2 CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone) Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle. Rituximab 375 mg/m^2 Rituximab Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
- Primary Outcome Measures
Name Time Method Percentage of Patients Who Developed Grade 3 or 4 Infusion-related Reactions (IRR) Resulting From Faster Infusion of Rituximab During Days 1 and 2 of Cycle 2 Days 1 and 2 of Cycle 2 The percentage of patients who developed Grade 3 or 4 IRRs resulting from faster infusion of rituximab at Cycle 2 was assessed in patients who had previously received rituximab at the standard infusion rate without experiencing a Grade 3 or 4 IRR at Cycle 1. IRRs were a predefined list of Medical Dictionary for Regulatory Activities (MedDRA) terms for infusion-related adverse events occurring on the day of and/or the day after rituximab infusion. The list of IRR terms was compiled based on IRRs observed in the present and previous studies in which rituximab was infused at the standard rate.
- Secondary Outcome Measures
Name Time Method Percentage of Patients Who Had an Adverse Event of Any Grade or Seriousness During Cycle 1 Cycle 1 Duration of Rituximab Infusion Including Dose Interruption Times Day 1 of each of Cycles 1 to 6 or 8 The median duration of the rituximab infusion on Day 1 of each cycle, including the duration of dose interruptions, is reported.
Percentage of Patients Who Had Undetectable Levels of CD19+ Lymphocytes at Cycle 2 and Either Cycle 6 or 8 (Last Cycle) Day 1 of Cycle 2 and either Cycle 6 or 8 (last cycle) Serum samples for measurement of CD19+ lymphocytes were taken pre-dose (within 15 minutes before rituximab infusion). CD19+ lymphocyte counts were measured by flow cytometry using a fluorescent-activated cell sorter (FACS).
Percentage of Patients Who Had an Adverse Event of Any Grade or Seriousness During Cycle 2 Through Cycle 6 or 8 (End of Study) Cycle 2 through Cycle 6 or 8 (end of study) Maximum Serum Concentration (Cmax) of Rituximab Post-dose at the First Alternative Dosing Rate (Cycle 2) and the Last Cycle (Either Cycle 6 or 8) Day 1 of Cycles 2 and either 6 or 8 (last cycle) Serum samples for rituximab pharmacokinetic analysis were taken pre-dose (within 15 minutes before rituximab infusion) and post-dose (within 15 minutes after the end of the rituximab infusion) after the first faster infusion (Cycle 2) and after the last infusion (either Cycle 6 or 8). An enzyme-linked immunosorbent assay (ELISA) was used to measure rituximab levels in the serum samples.