Non-Hodgkin's LymphomaPhase 3RATENCT00719472
A Study of Rituximab Alternative Dosing Rate in Patients With Previously Untreated Diffuse Large B-cell or Follicular Non-Hodgkin's Lymphoma (RATE)
A Phase 3 study testing Rituximab, CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone) and CVP (cyclophosphamide, vincristine, prednisone) in people with Non-Hodgkin's Lymphoma, run by Genentech, Inc..
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin's Lymphoma
- What is being tested?
- Rituximab, CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone) and CVP (cyclophosphamide, vincristine, prednisone)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 451 participants
- Where
- No sites listed yet
- Study dates
- Jul 2008to May 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
Official title: 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
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).
- Conditions
- Non-Hodgkin's Lymphoma
- Being tested
- Rituximab, CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone), CVP (cyclophosphamide, vincristine, prednisone), Analgesic/antipyretic and antihistamine drugs
- Keywords
- Follicular NHL, NHL, Large B-Cell NHL
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
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.
CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone)Drug
Commercial preparations of CHOP were used. Prednisone was administered prior to rituximab infusion.
CVP (cyclophosphamide, vincristine, prednisone)Drug
Commercial preparations of CVP were used. Prednisone was administered prior to rituximab infusion.
Analgesic/antipyretic and antihistamine drugsDrug
An analgesic/antipyretic (eg, acetaminophen) and an antihistamine (eg, diphenhydramine) were administered 30 minutes before each infusion of rituximab.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab 375 mg/m^2 | Experimental | 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. Receives: Drug: Rituximab; Drug: CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone); Drug: CVP (cyclophosphamide, vincristine, prednisone); Drug: Analgesic/antipyretic and antihistamine drugs |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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.
Measured: Days 1 and 2 of Cycle 2
Secondary outcomes (5)
Percentage of Patients Who Had an Adverse Event of Any Grade or Seriousness During Cycle 1
Measured: 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)
Measured: Cycle 2 through Cycle 6 or 8 (end of study)
Duration of Rituximab Infusion Including Dose Interruption Times
The median duration of the rituximab infusion on Day 1 of each cycle, including the duration of dose interruptions, is reported.
Measured: Day 1 of each of Cycles 1 to 6 or 8
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)
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.
Measured: Day 1 of Cycles 2 and either 6 or 8 (last cycle)
Percentage of Patients Who Had Undetectable Levels of CD19+ Lymphocytes at 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).
Measured: Day 1 of Cycle 2 and either Cycle 6 or 8 (last cycle)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 451 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Deborah Hurst, M.D., Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00719472
- Sponsor's protocol ID
- U4391g
- Acronym
- RATE
- Status last verified
- Apr 2017
- First submitted
- 18 Jul 2008
- Last updated
- 15 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00719472
- Acronym / sponsor ID
- RATE / U4391g
- Conditions
- Non-Hodgkin's Lymphoma
- Keywords
- Follicular NHL, NHL, Large B-Cell NHL
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 451 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 21 Jul 2008 (estimated)
- Results
- Posted 26 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab 375 mg/m^2 | Experimental | Drug: Rituximab, Drug: CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone), Drug: CVP (cyclophosphamide, vincristine, prednisone), Drug: Analgesic/antipyretic and antihistamine drugsPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabDuring 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 | Rituximab 375 mg/m^2 |
| CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone)Commercial preparations of CHOP were used. Prednisone was administered prior to rituximab infusion. | Drug | Rituximab 375 mg/m^2 |
| CVP (cyclophosphamide, vincristine, prednisone)Commercial preparations of CVP were used. Prednisone was administered prior to rituximab infusion. | Drug | Rituximab 375 mg/m^2 |
| Analgesic/antipyretic and antihistamine drugsAn analgesic/antipyretic (eg, acetaminophen) and an antihistamine (eg, diphenhydramine) were administered 30 minutes before each infusion of rituximab. | Drug | Rituximab 375 mg/m^2 |
Primary outcome
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.
5 secondary outcomes
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
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deborah Hurst, M.D. study director
Genentech, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab, CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone) and CVP (cyclophosphamide, vincristine, prednisone) in people with Non-Hodgkin's Lymphoma, run by Genentech, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.