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)
- Conditions
- Follicular Lymphoma
- Registration Number
- NCT02213263
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 394
- Confirmed diagnosis of low tumor burden, CD20-positive follicular lymphoma
- Ann Arbor Stage II, III, or IV
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR): Percentage of Participants With Overall Response (OR) at Week 26 Week 26 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
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline up to Week 52 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.
Number of Participants With Clinically Significant Laboratory Abnormalities Baseline up to Week 52 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.
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 Baseline up to Week 52 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.
Percentage of Participants With Complete Remission (CR) at Week 26 Week 26 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.
Duration of Response (DOR) 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 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.
Time to Treatment Failure (TTF) From randomization until disease progression, death or permanent discontinuation from treatment/study due to any reason, or up to Week 52 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.
Progression-Free Survival (PFS) From randomization until disease progression or death due to any cause or up to Week 52 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.
Overall Survival From randomization until death due to any cause or up to Week 52 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.
Number of Participants With Treatment Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline up to Week 52 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.
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 Baseline up to Week 52 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.
Maximum Observed Serum Concentration (Cmax) of PF-05280586 and Rituximab-EU 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 Cluster of Differentiation (CD) 19-Positive B-Cell Counts Baseline, Week 2, 3, 4, 5, 13, 26, 39, 52 Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) Baseline up to Week 52 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.
Minimum Observed (Trough) Serum Concentration (Ctrough) of PF-05280586 and Rituximab-EU Predose (within 4 hours prior to the start of dosing) on Day 1, 8, 15, and 22 Number of Participants Reporting Immune-Based Adverse Effects Baseline up to Week 52 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).
Trial Locations
- Locations (376)
Pacific Cancer Medical Center, Inc.
🇺🇸Anaheim, California, United States
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Compassionate Care Research Group, Inc., at Compassionate Cancer Care Medical Group, Inc.
🇺🇸Riverside, California, United States
Global Cancer Research Institute (GCRI), Inc
🇺🇸Gilroy, California, United States
Saint Louise Regional Hospital Radiology Department (Radiology Only)
🇺🇸Gilroy, California, United States
South Valley Imaging Center (Imaging Only)
🇺🇸Gilroy, California, United States
Los Angeles Hematology Oncology Medical Group
🇺🇸Los Angeles, California, United States
Comprehensive Cancer Center at Desert Regional Medical Center
🇺🇸Palm Springs, California, United States
Torrance Health Association DBA, Torrance Memorial Physician, Network/Cancer Care Associates
🇺🇸Redondo Beach, California, United States
Global Cancer Research Institute, Inc.
🇺🇸San Jose, California, United States
Scroll for more (366 remaining)Pacific Cancer Medical Center, Inc.🇺🇸Anaheim, California, United States