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A Study of Rituximab Alternative Dosing Rate in Patients With Previously Untreated Diffuse Large B-cell or Follicular Non-Hodgkin's Lymphoma (RATE) (RATE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00719472
Recruitment Status : Completed
First Posted : July 21, 2008
Results First Posted : June 26, 2012
Last Update Posted : May 15, 2017
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE July 18, 2008
First Posted Date  ICMJE July 21, 2008
Results First Submitted Date  ICMJE May 24, 2012
Results First Posted Date  ICMJE June 26, 2012
Last Update Posted Date May 15, 2017
Study Start Date  ICMJE July 2008
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2012)
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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 18, 2008)
Development of a Grade 3 or 4 infusion-related toxicity (targeted adverse event) [ Time Frame: Cycle 2 ]
Change History Complete list of historical versions of study NCT00719472 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2012)
  • Percentage of Patients Who Had an Adverse Event of Any Grade or Seriousness During Cycle 1 [ Time Frame: Cycle 1 ]
  • Percentage of Patients Who Had an Adverse Event of Any Grade or Seriousness During Cycle 2 Through Cycle 6 or 8 (End of Study) [ Time Frame: Cycle 2 through Cycle 6 or 8 (end of study) ]
  • Duration of Rituximab Infusion Including Dose Interruption Times [ Time Frame: 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.
  • 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) [ Time Frame: 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.
  • Percentage of Patients Who Had Undetectable Levels of CD19+ Lymphocytes at Cycle 2 and Either Cycle 6 or 8 (Last Cycle) [ Time Frame: 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2008)
  • All adverse events regardless of grade or seriousness [ Time Frame: Length of study ]
  • Duration (in minutes) of rituximab administration by cycle [ Time Frame: Length of study ]
  • Rituximab pharmacokinetics as determined by serum rituximab levels during the first rituximab alternative dosing rate (Cycle 2) and the last cycle (either Cycle 6 or 8) of the treatment regimen [ Time Frame: Cycle 2 and the last cycle ]
  • Pharmacodynamics during the first rituximab alternative dosing rate (Cycle 2) and the last cycle (either Cycle 6 or 8) of the treatment regimen [ Time Frame: Cycle 2 and the last cycle ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Rituximab Alternative Dosing Rate in Patients With Previously Untreated Diffuse Large B-cell or Follicular Non-Hodgkin's Lymphoma (RATE)
Official Title  ICMJE A Phase III Multicenter, Open-label Study of Rituximab Alternative Dosing Rate in Patients With Previously Untreated Diffuse Large B-cell or Follicular Non-Hodgkin's Lymphoma
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Hodgkin's Lymphoma
Intervention  ICMJE
  • Drug: Rituximab
    During Cycle 1 rituximab was administered at an initial rate of 50 mg/hour. In the absence of infusion toxicity during Cycle 1, the infusion rate was escalated by 50 mg/h increments every 30 minutes to a maximum rate of 400 mg/hour. In case of infusion-related reactions, the infusion was interrupted or the infusion rate reduced. In case of Grade 3/4 infusion reactions, the rituximab infusion was discontinued and medical treatment provided. If the rituximab infusion in Cycle 1 was tolerated without a serious adverse event (AE) or Grade 3/4 infusion-related AE, as judged by the investigator, infusions in Cycle 2 onwards were administered as follows: 20% of the total dose was given over 30 minutes and the remaining 80% of the dose was given over the next 60 minutes, for a total infusion time of 90 minutes. Commercial preparations of rituximab were used.
  • Drug: CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone)
    Commercial preparations of CHOP were used. Prednisone was administered prior to rituximab infusion.
  • Drug: CVP (cyclophosphamide, vincristine, prednisone)
    Commercial preparations of CVP were used. Prednisone was administered prior to rituximab infusion.
  • Drug: Analgesic/antipyretic and antihistamine drugs
    An analgesic/antipyretic (eg, acetaminophen) and an antihistamine (eg, diphenhydramine) were administered 30 minutes before each infusion of rituximab.
Study Arms  ICMJE Experimental: Rituximab 375 mg/m^2
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.
Interventions:
  • Drug: Rituximab
  • Drug: CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone)
  • Drug: CVP (cyclophosphamide, vincristine, prednisone)
  • Drug: Analgesic/antipyretic and antihistamine drugs
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 22, 2010)
451
Original Estimated Enrollment  ICMJE
 (submitted: July 18, 2008)
385
Actual Study Completion Date  ICMJE May 2011
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

* 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00719472
Other Study ID Numbers  ICMJE U4391g
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Deborah Hurst, M.D. Genentech, Inc.
PRS Account Genentech, Inc.
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP