Clinical Trials /

A Study Of PF-05280586 (Rituximab-Pfizer) Or MabThera® (Rituximab-EU) For The First-Line Treatment Of Patients With CD20-Positive, Low Tumor Burden, Follicular Lymphoma (REFLECTIONS B328-06)

NCT02213263

Description:

This study will compare the safety and effectiveness of PF-05280586 versus rituximab-EU in patients with CD20-positive, low tumor burden follicular lymphoma. The primary hypothesis to be tested in this study is that the effectiveness of PF-05280586, as measured by the Overall Response Rate, is similar to that of rituximab-EU.

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Completed

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT02213263

Trial Eligibility

Document

Title

  • Brief Title: A Study Of PF-05280586 (Rituximab-Pfizer) Or MabThera® (Rituximab-EU) For The First-Line Treatment Of Patients With CD20-Positive, Low Tumor Burden, Follicular Lymphoma (REFLECTIONS B328-06)
  • Official Title: A PHASE 3, RANDOMIZED, DOUBLE-BLIND STUDY OF PF-05280586 VERSUS RITUXIMAB FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH CD20-POSITIVE, LOW TUMOR BURDEN, FOLLICULAR LYMPHOMA

Clinical Trial IDs

  • ORG STUDY ID: B3281006
  • SECONDARY ID: 2014-000132-41
  • SECONDARY ID: REFLECTIONS
  • NCT ID: NCT02213263

Conditions

  • Follicular Lymphoma

Interventions

DrugSynonymsArms
PF-05280586PF-05280586
MabThera®MabThera®

Purpose

This study will compare the safety and effectiveness of PF-05280586 versus rituximab-EU in patients with CD20-positive, low tumor burden follicular lymphoma. The primary hypothesis to be tested in this study is that the effectiveness of PF-05280586, as measured by the Overall Response Rate, is similar to that of rituximab-EU.

Trial Arms

NameTypeDescriptionInterventions
PF-05280586Experimental
  • PF-05280586
MabThera®Active Comparator
  • MabThera®

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of low tumor burden, CD20-positive follicular lymphoma

          -  Ann Arbor Stage II, III, or IV

        Exclusion Criteria:

          -  Not a candidate for treatment with rituximab as a single-agent

          -  Evidence of transformation to a high grade or diffuse large B-cell lymphoma

          -  Any previous systemic therapy for B-cell NHL, including chemotherapy, immunotherapy,
             or steroids

          -  Any prior treatment with rituximab

          -  Active, uncontrolled infection
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR): Percentage of Participants With Overall Response (OR) at Week 26
Time Frame:Week 26
Safety Issue:
Description:ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) in accordance with the revised response criteria for malignant lymphoma (Cheson 2007). CR was defined as disappearance of all evidence of disease. PR was defined as regression of measureable disease and no new sites.

Secondary Outcome Measures

Measure:Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:Baseline up to Week 52
Safety Issue:
Description:An AE was any untoward medical occurrence in participants who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious.
Measure:Number of Participants With Treatment Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:Baseline up to Week 52
Safety Issue:
Description:Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. Relatedness to treatment was assessed by investigator. AEs included both serious and non-serious AEs.
Measure:Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03
Time Frame:Baseline up to Week 52
Safety Issue:
Description:An AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 1=Mild, asymptomatic or mild symptoms, Grade 2=Moderate; minimal, local or noninvasive intervention indicated, Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life threatening) events caused participant to be in imminent danger of death. Grade 5 = death. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state.
Measure:Number of Participants With Grade 3 or Higher Treatment-Related Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03
Time Frame:Baseline up to Week 52
Safety Issue:
Description:Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Grade 1=Mild, asymptomatic or mild symptoms, Grade 2=Moderate; minimal, local or noninvasive intervention indicated; Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 = death. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state.
Measure:Number of Participants With Clinically Significant Laboratory Abnormalities
Time Frame:Baseline up to Week 52
Safety Issue:
Description:Criteria for clinically significant laboratory abnormalities included total bilirubin (TB) less than (<) 2*upper limit of normal (ULN), alanine aminotransferase (ALT)<3*ULN; TB<2*ULN, ALT more than (>) 3 equal to (=) *ULN; TB<2*ULN, aspartate aminotransferase (AST)<3*ULN; TB<2*ULN, AST>=3*ULN. Data for only those categories are reported for which at least one participant had clinically significant laboratory abnormality.
Measure:Time to Treatment Failure (TTF)
Time Frame:From randomization until disease progression, death or permanent discontinuation from treatment/study due to any reason, or up to Week 52
Safety Issue:
Description:TTF was defined as the time (in months) from date of randomization to first progression of disease based on central review, death due to any cause, or permanent discontinuation from treatment, or discontinuation from study for any reason, whichever came first. Progression was defined as any new lesion or increase by greater than or equal to (>=) 50% of previously involved sites from nadir. TTF was calculated using Kaplan-Meier method.
Measure:Progression-Free Survival (PFS)
Time Frame:From randomization until disease progression or death due to any cause or up to Week 52
Safety Issue:
Description:PFS was defined as the time (in months) from date of randomization to first progression of disease (PD) based on central review or death due to any cause in the absence of documented PD. PD was defined as any new lesion or increase by >=50% of previously involved sites from nadir. PFS was calculated using Kaplan-Meier method.
Measure:Percentage of Participants With Complete Remission (CR) at Week 26
Time Frame:Week 26
Safety Issue:
Description:Complete Remission (CR) was defined as disappearance of all evidence of disease. CR was assessed by central review based on scans done at Week 26.
Measure:Duration of Response (DOR)
Time Frame:From date of first documentation of overall response to first documentation of PD or to death due to any cause in absence of PD or up to Week 52
Safety Issue:
Description:DOR was defined as the time (in months) from date of the first documentation of overall response (CR or PR) to the first documentation of progressive disease (PD) based on central review or to death due to any cause in the absence of documented PD. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measureable disease and no new sites. PD was defined as any new lesion or increase by >=50% of previously involved sites from nadir. DOR was calculated using Kaplan-Meier method.
Measure:Overall Survival
Time Frame:From randomization until death due to any cause or up to Week 52
Safety Issue:
Description:Overall survival was defined as the time (in months) from date of randomization to death due to any cause. For participants who were alive, overall survival was censored at the last contact. Overall survival was calculated using Kaplan-Meier method.
Measure:Maximum Observed Serum Concentration (Cmax) of PF-05280586 and Rituximab-EU
Time Frame:Predose (within 4 hours prior to start of infusion) on Days 1, 8, 15 and 22; within 15 minutes prior to end of infusion on Days 1 and 22
Safety Issue:
Description:
Measure:Minimum Observed (Trough) Serum Concentration (Ctrough) of PF-05280586 and Rituximab-EU
Time Frame:Predose (within 4 hours prior to the start of dosing) on Day 1, 8, 15, and 22
Safety Issue:
Description:
Measure:Cluster of Differentiation (CD) 19-Positive B-Cell Counts
Time Frame:Baseline, Week 2, 3, 4, 5, 13, 26, 39, 52
Safety Issue:
Description:
Measure:Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
Time Frame:Baseline up to Week 52
Safety Issue:
Description:Human serum ADA samples were analyzed for the presence or absence of anti-rituximab antibodies or anti-PF-05280586 antibodies using the validated drug-specific assay with a tiered approach using screening, confirmation and titer/quantitation. Human NAb serum samples testing ADA positive were analyzed for the presence or absence of neutralizing anti-rituximab antibody and neutralizing anti-PF-05280586 antibody using the validated drug-specific assay with a tiered approach using screening, confirmation and titer/quantitation. Participants with their ADA titer >= 1.88 were considered to be ADA positive. Only participants with a positive ADA result were further tested for NAb.
Measure:Number of Participants Reporting Immune-Based Adverse Effects
Time Frame:Baseline up to Week 52
Safety Issue:
Description:Immune-based adverse effects included infusion related reaction (IRR), adverse events which fulfill Sampson's criteria, and adverse events which belong to the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) anaphylaxis or hypersensitivity reactions. Potential allergic and anaphylactic reactions were identified programmatically based on the criteria of Sampson et al, (2006).

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Pfizer

Trial Keywords

  • rituximab
  • follicular lymphoma
  • Non-Hodgkin lymphoma
  • Non-Hodgkin's lymphoma

Last Updated

June 20, 2019