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

Purpose

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).

Condition	Intervention	Phase
Non-Hodgkin's Lymphoma	Drug: Rituximab Drug: CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone) Drug: CVP (cyclophosphamide, vincristine, prednisone) Drug: Analgesic/antipyretic and antihistamine drugs	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cold and Cough Medicines Lymphoma Steroids

Drug Information available for: Cyclophosphamide Histamine Prednisone Vincristine sulfate Doxorubicin Doxorubicin hydrochloride Rituximab

U.S. FDA Resources

Further study details as provided by Genentech:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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:

Percentage of Patients Who Had an Adverse Event of Any Grade or Seriousness During Cycle 1 [ Time Frame: Cycle 1 ] [ Designated as safety issue: Yes ]
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) ] [ Designated as safety issue: Yes ]
Duration of Rituximab Infusion Including Dose Interruption Times [ Time Frame: Day 1 of each of Cycles 1 to 6 or 8 ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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).

Enrollment:	451
Study Start Date:	July 2008
Study Completion Date:	May 2011
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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.

Arms

Assigned Interventions

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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00719472

Sponsors and Collaborators

Genentech

Investigators

Study Director:

Deborah Hurst, M.D.

Genentech

More Information

No publications provided

Responsible Party:	Genentech
ClinicalTrials.gov Identifier:	NCT00719472 History of Changes
Other Study ID Numbers:	U4391g
Study First Received:	July 18, 2008
Results First Received:	May 24, 2012
Last Updated:	July 11, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genentech:

Follicular NHL
NHL
Large B-Cell NHL

Additional relevant MeSH terms:

Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Analgesics
Histamine Antagonists
Histamine H1 Antagonists
Antipyretics
Cyclophosphamide
Rituximab

Doxorubicin
Prednisone
Vincristine
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 23, 2013