Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-Hodgkin's Lymphoma
Interventions Drug: Rituximab
Drug: CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone)
Drug: CVP (cyclophosphamide, vincristine, prednisone)
Drug: Analgesic/antipyretic and antihistamine drugs
Enrollment 451
Recruitment Details  
Pre-assignment Details Of 451 enrolled patients, 26 withdrew before receiving treatment and are not included in the Baseline Characteristics nor any of the Outcome Measures.
Arm/Group Title Rituximab 375 mg/m^2
Hide Arm/Group Description 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.
Period Title: Enrolled in Study
Started 451
Completed 425
Not Completed 26
Reason Not Completed
Physician decision to withdraw patient             1
Subject decision to withdraw             8
Various Reasons             17
Period Title: Received Cycle 1 Treatment
Started 425
Completed 372
Not Completed 53
Reason Not Completed
Adverse Event             8
Death             5
Eligibility criteria for Cycle 2 not met             11
Physician decision to withdraw patient             7
Subject decision to withdraw             9
Various Reasons             13
Period Title: Received Cycle 2 Treatment
Started 372
Completed 304
Not Completed 68
Reason Not Completed
Adverse Event             12
Death             6
Disease progression             3
Lost to Follow-up             3
Physician decision to withdraw patient             13
Subject decision to withdraw             6
Various Reasons             25
Arm/Group Title Rituximab 375 mg/m^2
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 425
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 425 participants
62.7  (13.4)
[1]
Measure Description: Demographic data are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab regardless of infusion rate. Of the 451 enrolled patients, 26 withdrew before receiving treatment and were not included in the ITT population.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 425 participants
Female
191
  44.9%
Male
234
  55.1%
[1]
Measure Description: Demographic data are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab regardless of infusion rate. Of the 451 enrolled patients, 26 withdrew before receiving treatment and were not included in the ITT population.
1.Primary Outcome
Title 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
Hide Description 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.
Time Frame Days 1 and 2 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol evaluable population: All patients who received rituximab by faster infusion in Cycle 2 and who did not experience a Grade 3 or 4 infusion-related reaction during the rituximab infusion given at the standard rate during Cycle 1.
Arm/Group Title Rituximab 375 mg/m^2
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 363
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
1.1
(0.3 to 2.8)
2.Secondary Outcome
Title Percentage of Patients Who Had an Adverse Event of Any Grade or Seriousness During Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: All patients who received at least 1 dose of rituximab regardless of infusion rate.
Arm/Group Title Rituximab 375 mg/m^2
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 425
Measure Type: Number
Unit of Measure: Percentage of participants
91.8
3.Secondary Outcome
Title Percentage of Patients Who Had an Adverse Event of Any Grade or Seriousness During Cycle 2 Through Cycle 6 or 8 (End of Study)
Hide Description [Not Specified]
Time Frame Cycle 2 through Cycle 6 or 8 (end of study)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol evaluable population: All patients who received rituximab by faster infusion in Cycle 2 and who did not experience a Grade 3 or 4 infusion-related reaction during the rituximab infusion given at the standard rate during Cycle 1.
Arm/Group Title Rituximab 375 mg/m^2
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 363
Measure Type: Number
Unit of Measure: Percentage of participants
98.6
4.Secondary Outcome
Title Duration of Rituximab Infusion Including Dose Interruption Times
Hide Description The median duration of the rituximab infusion on Day 1 of each cycle, including the duration of dose interruptions, is reported.
Time Frame Day 1 of each of Cycles 1 to 6 or 8
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol evaluable population: All patients who received rituximab by faster infusion in Cycle 2 and who did not experience a Grade 3 or 4 infusion-related reaction during the rituximab infusion given at the standard rate during Cycle 1.
Arm/Group Title Rituximab 375 mg/m^2
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 363
Median (Inter-Quartile Range)
Unit of Measure: Minutes
Cycle 1 (n=362)
245
(225 to 273)
Cycle 2 (n=363)
91
(90 to 98)
Cycle 3 (n=344)
91
(90 to 98)
Cycle 4 (n=329)
91
(90 to 96)
Cycle 5 (n=312)
91
(90 to 95)
Cycle 6 (n=303)
91
(90 to 96)
Cycle 7 (n=59)
91
(90 to 95)
Cycle 8 (n=59)
91
(90 to 95)
5.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Day 1 of Cycles 2 and either 6 or 8 (last cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic evaluable population: All patients who received at least 1 infusion of rituximab and had rituximab concentration data.
Arm/Group Title Rituximab 375 mg/m^2
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 335
Mean (Standard Deviation)
Unit of Measure: µg/mL
Cycle 2 (n=335) 228.0  (63.7)
Cycle 6 (n=238) 275.0  (71.5)
Cycle 8 (n=36) 299.0  (90.6)
6.Secondary Outcome
Title Percentage of Patients Who Had Undetectable Levels of CD19+ Lymphocytes at Cycle 2 and Either Cycle 6 or 8 (Last Cycle)
Hide Description 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).
Time Frame Day 1 of Cycle 2 and either Cycle 6 or 8 (last cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol evaluable population: All patients who received rituximab by faster infusion in Cycle 2 and who did not experience a Grade 3 or 4 infusion-related reaction during the rituximab infusion given at the standard rate during Cycle 1. Only patients with pre-dose CD19+ lymphocyte counts at each time point were included in the analyses.
Arm/Group Title Rituximab 375 mg/m^2
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 338
Measure Type: Number
Unit of Measure: Percentage of participants
Cycle 2 (n=338) 50.5
Cycle 6 (n=240) 68.3
Cycle 8 (n=32) 87.5
Time Frame Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier.
Adverse Event Reporting Description Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
 
Arm/Group Title Rituximab 375 mg/m^2
Hide Arm/Group Description 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.
All-Cause Mortality
Rituximab 375 mg/m^2
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Rituximab 375 mg/m^2
Affected / at Risk (%)
Total   107/425 (25.18%) 
Blood and lymphatic system disorders   
Febrile neutropenia  1  33/425 (7.76%) 
Neutropenia  1  10/425 (2.35%) 
Pancytopenia  1  7/425 (1.65%) 
Anaemia  1  5/425 (1.18%) 
Leukopenia  1  1/425 (0.24%) 
Thrombocytopenia  1  1/425 (0.24%) 
Cardiac disorders   
Cardiac arrest  1  2/425 (0.47%) 
Ventricular tachycardia  1  2/425 (0.47%) 
Cardiac failure congestive  1  3/425 (0.71%) 
Atrial fibrillation  1  3/425 (0.71%) 
Cardiomyopathy  1  1/425 (0.24%) 
Acute myocardial infarction  1  1/425 (0.24%) 
Gastrointestinal disorders   
Abdominal pain  1  6/425 (1.41%) 
Nausea  1  3/425 (0.71%) 
Vomiting  1  3/425 (0.71%) 
Constipation  1  3/425 (0.71%) 
Small intestinal obstruction  1  2/425 (0.47%) 
Pancreatitis  1  1/425 (0.24%) 
Colitis  1  1/425 (0.24%) 
Diarrhoea  1  1/425 (0.24%) 
Faecaloma  1  1/425 (0.24%) 
Gastric perforation  1  1/425 (0.24%) 
Gastritis  1  1/425 (0.24%) 
Intestinal mass  1  1/425 (0.24%) 
Dysphagia  1  1/425 (0.24%) 
Haemorrhoids  1  1/425 (0.24%) 
Small intestinal perforation  1  1/425 (0.24%) 
Colonic obstruction  1  1/425 (0.24%) 
Megacolon  1  1/425 (0.24%) 
Gastrointestinal haemorrhage  1  1/425 (0.24%) 
Stomatitis  1  1/425 (0.24%) 
General disorders   
Pyrexia  1  3/425 (0.71%) 
Chest pain  1  3/425 (0.71%) 
Asthenia  1  2/425 (0.47%) 
Hepatobiliary disorders   
Hepatic failure  1  2/425 (0.47%) 
Ischaemic hepatitis  1  1/425 (0.24%) 
Infections and infestations   
Pneumonia  1  7/425 (1.65%) 
Bronchitis  1  1/425 (0.24%) 
Lung infection  1  1/425 (0.24%) 
Sepsis  1  5/425 (1.18%) 
Device related sepsis  1  1/425 (0.24%) 
Fungal sepsis  1  1/425 (0.24%) 
Neutropenic sepsis  1  1/425 (0.24%) 
Septic shock  1  1/425 (0.24%) 
Staphylococcal infection  1  2/425 (0.47%) 
Staphylococcal sepsis  1  1/425 (0.24%) 
Pseudomonal sepsis  1  2/425 (0.47%) 
Gastroenteritis  1  1/425 (0.24%) 
Cellulitis  1  1/425 (0.24%) 
Mastitis  1  1/425 (0.24%) 
Meningitis aseptic  1  1/425 (0.24%) 
Hepatitis B  1  1/425 (0.24%) 
Herpes zoster  1  1/425 (0.24%) 
Streptococcal bacteraemia  1  1/425 (0.24%) 
Urinary tract infection  1  1/425 (0.24%) 
Injury, poisoning and procedural complications   
Fall  1  1/425 (0.24%) 
Wound dehiscence  1  1/425 (0.24%) 
Accidental overdose  1  1/425 (0.24%) 
Metabolism and nutrition disorders   
Dehydration  1  12/425 (2.82%) 
Failure to thrive  1  1/425 (0.24%) 
Malnutrition  1  1/425 (0.24%) 
Decreased appetite  1  1/425 (0.24%) 
Hypercalcaemia  1  1/425 (0.24%) 
Hypoglycaemia  1  1/425 (0.24%) 
Hypokalaemia  1  1/425 (0.24%) 
Musculoskeletal and connective tissue disorders   
Muscular weakness  1  1/425 (0.24%) 
Musculoskeletal pain  1  1/425 (0.24%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Breast cancer  1  1/425 (0.24%) 
Lymphoma  1  1/425 (0.24%) 
Nervous system disorders   
Cerebrovascular accident  1  2/425 (0.47%) 
Cerebral ischaemia  1  1/425 (0.24%) 
Convulsion  1  1/425 (0.24%) 
Psychiatric disorders   
Anxiety  1  1/425 (0.24%) 
Renal and urinary disorders   
Renal failure  1  1/425 (0.24%) 
Renal failure acute  1  1/425 (0.24%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  2/425 (0.47%) 
Respiratory distress  1  1/425 (0.24%) 
Acute respiratory failure  1  2/425 (0.47%) 
Respiratory failure  1  2/425 (0.47%) 
Pneumonia aspiration  1  1/425 (0.24%) 
Pleural effusion  1  1/425 (0.24%) 
Vascular disorders   
Deep vein thrombosis  1  3/425 (0.71%) 
Jugular vein thrombosis  1  1/425 (0.24%) 
Venous thrombosis limb  1  1/425 (0.24%) 
Hypotension  1  2/425 (0.47%) 
Orthostatic hypotension  1  1/425 (0.24%) 
Thrombosis  1  1/425 (0.24%) 
Superior vena cava syndrome  1  1/425 (0.24%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rituximab 375 mg/m^2
Affected / at Risk (%)
Total   421/425 (99.06%) 
Blood and lymphatic system disorders   
Neutropenia  1  135/425 (31.76%) 
Anaemia  1  100/425 (23.53%) 
Thrombocytopenia  1  55/425 (12.94%) 
Leukopenia  1  31/425 (7.29%) 
Gastrointestinal disorders   
Nausea  1  202/425 (47.53%) 
Vomiting  1  69/425 (16.24%) 
Constipation  1  142/425 (33.41%) 
Diarrhoea  1  99/425 (23.29%) 
Abdominal pain  1  43/425 (10.12%) 
Dyspepsia  1  51/425 (12.00%) 
Stomatitis  1  34/425 (8.00%) 
Dry mouth  1  37/425 (8.71%) 
General disorders   
Fatigue  1  227/425 (53.41%) 
Asthenia  1  47/425 (11.06%) 
Pain  1  30/425 (7.06%) 
Chest pain  1  23/425 (5.41%) 
Pyrexia  1  63/425 (14.82%) 
Chills  1  49/425 (11.53%) 
Oedema peripheral  1  44/425 (10.35%) 
Mucosal inflammation  1  43/425 (10.12%) 
Infections and infestations   
Upper respiratory tract infection  1  27/425 (6.35%) 
Candidiasis  1  22/425 (5.18%) 
Investigations   
Weight decreased  1  33/425 (7.76%) 
Metabolism and nutrition disorders   
Decreased appetite  1  72/425 (16.94%) 
Dehydration  1  36/425 (8.47%) 
Hypokalaemia  1  29/425 (6.82%) 
Hypomagnesaemia  1  26/425 (6.12%) 
Hyperglycaemia  1  23/425 (5.41%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  56/425 (13.18%) 
Pain in extremity  1  24/425 (5.65%) 
Bone pain  1  41/425 (9.65%) 
Arthralgia  1  43/425 (10.12%) 
Muscle spasms  1  30/425 (7.06%) 
Nervous system disorders   
Neuropathy peripheral  1  99/425 (23.29%) 
Peripheral sensory neuropathy  1  37/425 (8.71%) 
Dysgeusia  1  58/425 (13.65%) 
Headache  1  75/425 (17.65%) 
Dizziness  1  59/425 (13.88%) 
Paraesthesia  1  33/425 (7.76%) 
Psychiatric disorders   
Insomnia  1  100/425 (23.53%) 
Anxiety  1  42/425 (9.88%) 
Depression  1  22/425 (5.18%) 
Respiratory, thoracic and mediastinal disorders   
Oropharyngeal pain  1  37/425 (8.71%) 
Dyspnoea  1  57/425 (13.41%) 
Cough  1  65/425 (15.29%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  169/425 (39.76%) 
Rash  1  45/425 (10.59%) 
Hyperhidrosis  1  24/425 (5.65%) 
Pruritus  1  28/425 (6.59%) 
Vascular disorders   
Hypotension  1  26/425 (6.12%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Genentech, Inc.
Phone: 800-821-8590
Layout table for additonal information
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00719472    
Other Study ID Numbers: U4391g
First Submitted: July 18, 2008
First Posted: July 21, 2008
Results First Submitted: May 24, 2012
Results First Posted: June 26, 2012
Last Update Posted: May 15, 2017