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

NCT00719472 | Completed Phase 3 Results

• 1 other identifier: U4391g
• Study Type: interventional
• Target: 451
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Non-Hodgkin's Lymphoma

Keywords

Follicular NHL; NHL; Large B-Cell NHL

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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)

  Cycle 2 through Cycle 6 or 8 (end of study)

• Duration of Rituximab Infusion Including Dose Interruption Times

  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)

  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)

  Day 1 of Cycle 2 and either Cycle 6 or 8 (last cycle)

Study Arms (1)

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.

Drug: Rituximab; Drug: CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone); Drug: CVP (cyclophosphamide, vincristine, prednisone); Drug: Analgesic/antipyretic and antihistamine drugs

Interventions

Rituximab DRUG

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.

Rituximab 375 mg/m^2

CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone) DRUG

Commercial preparations of CHOP were used. Prednisone was administered prior to rituximab infusion.

Rituximab 375 mg/m^2

CVP (cyclophosphamide, vincristine, prednisone) DRUG

Commercial preparations of CVP were used. Prednisone was administered prior to rituximab infusion.

Rituximab 375 mg/m^2

Analgesic/antipyretic and antihistamine drugs DRUG

An analgesic/antipyretic (eg, acetaminophen) and an antihistamine (eg, diphenhydramine) were administered 30 minutes before each infusion of rituximab.

Rituximab 375 mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \* 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

Sponsors & Collaborators

• Genentech, Inc.: lead

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; COP protocol 2; Analgesics; Antipyretics; Histamine Antagonists

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

800-821-8590

Study Officials

• Deborah Hurst, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2008
• First Posted: July 21, 2008
• Study Start: July 1, 2008
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: May 15, 2017
• Results First Posted: June 26, 2012

Record last verified: 2017-04