The purpose of this phase II open label study was is to evaluate the safety and efficacy of ofatumumab and bendamustine followed by maintenance ofatumumab in subjects with indolent B-NHL who had relapsed after Rituximab treatment. A maximum of 53 subjects at least 18 years old with Small lymphocytic, lymphoplasmacytic, marginal zone lymphoma, or follicular lymphoma; Grades 1, 2 and 3a, would have been enrolled (34 in Stage 1 and 19 in Stage 2). Subjects should have had Rituximab-sensitive disease, defined as a Partial Remission (PR) or Complete Remission (CR) to the last rituximab-containing therapy lasting at least 6 months following completion of therapy or subjects should have relapsed or have had disease progression following response to prior rituximab-based therapy a Eastern Cooperative Oncology Group (ECOG) Performance status of 0 1 or 2. During the induction phase, ofatumumab 1000 mg IV on day 1 of each cycle (cycles 1-6) were followed by Bendamustine 90 mg/m2 IV on days 1, 2 of each cycle (cycles 1-6).During the maintenance phase, subjects with a PR or CR after the induction phase received ofatumumab 1000 mg IV every 2 months for 2 years.
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Masking
NONE
Enrollment
49
1000 mg intravenous (IV) on day 1 of each cycle (cycles 1-6) for induction phase 1000 mg IV every 2 months for 2 years
90 mg/m2 on day 1 (after the ofatumumab infusion) and day 2 of each cycle (cycles 1-6)
Novartis Investigative Site
Chandler, Arizona, United States
Novartis Investigative Site
Burbank, California, United States
Novartis Investigative Site
Fresno, California, United States
Novartis Investigative Site
Oxnard, California, United States
Novartis Investigative Site
Aurora, Colorado, United States
Novartis Investigative Site
Orange Park, Florida, United States
Novartis Investigative Site
Burlington, Massachusetts, United States
Novartis Investigative Site
Omaha, Nebraska, United States
Novartis Investigative Site
Las Vegas, Nevada, United States
Novartis Investigative Site
Cary, North Carolina, United States
...and 12 more locations
Complete Remission (CR) Rate of Induction Therapy After Cycle 6 (28 Days) (FAS)
Complete response (CR) included all of the following: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. All target nodes had to have regressed to ≤ 1.5cm in the longest diameter. Non-measureable nodes 1.1 to 1.5cm in the longest diameter and \>1cm in the short axis at baseline had to regress to ≤ 1cm in the short axis by visual estimation; enlarged spleen or liver (with nodules) must have returned to normal size and nodules disappeared and if bone marrow was involved, infiltrate had to have cleared on repeat biopsy sample. CR was not valid without imaging data. The corresponding 2-sided 95% exact confidence interval (CI) of the response rate was estimated by the Clopper-Pearson method.
Time frame: Baseline up to 24 weeks
Overall Response Rate (ORR) During Induction Phase After Cycle 6 (FAS)
The overall response = CR (defined in Primary Outcome) + Partial Response (PR) which required all of the following: \> or = to 50% decrease from baseline in target nodules; \> or = to 50% decrease in hepatic/splenic nodules and no increase in liver or spleen size; no unequivocal progression in non-target lestions; no new sites of disease.
Time frame: Baseline up to 24 weeks
Conversion Rate of Partial Response in Induction Phase to Complete Response With Maintenance Ofatumumab (FAS)
Rate of conversion from PR in the Induction phase, to CR with maintenance ofatumumab in subjects who have a PR with induction therapy with ofatumumab and bendamustine
Time frame: Partial response in induction phase up to 24 weeks
Percentage of Participants With Progression Free Survival (PFS) up to 30 Months (FAS)
Progression free survival (PFS) is defined as the interval between first treatment and disease progression or death due to any cause. PFS criteria: A previously normal node (≤ 1.5 x ≤ 1.0cm), including nodes that were not previously visible, must increase to \>2.0 x ≥ 1.5cm; ≥ 50% increase from nadir in the PPD of any target node. The long axis must increase by at least 5 mm and to \>2.0cm.; ≥ 50% increase from nadir in the long axis of any target node. The long axis must increase by at least 5 mm and to \>2.0 cm.; ≥ 50% increase from nadir in the SPD of target nodes and at least one node should have a long axis \>1.5 cm.
Time frame: Baseline up to approximately 30 months
Kaplan-Meier Estimates of Progression Free Survival up to 30 Months (FAS)
Progression Free Survival (PFS) is defined as the interval between first treatment and disease progression or death due to any cause. PFS events: progression documented between scheduled visits, death before first PD assessment (or death at baseline or prior to any adequate assessments), death between adequate assessment visits. For the PFS analysis, the survival function was estimated using Kaplan-Meier estimates.
Time frame: Baseline up to approximately 30 months
Pharmacokinetic Profile Which Includes Measuring Blood Levels of Ofatumumab and Bendamustine in Combination and Ofatumumab Alone During Maintenance Treatment and Measuring Blood Levels of Circulating B Cell
Due to recruitment issues, this data analysis was not done per changes in planned analysis. This data was only presented as patient listings. The statistical analysis plan was modified to indicate that Pharmacokinetic/Pharmacodynamic exploratory analyses were not done.
Time frame: up to 30 months
All Deaths by Preferred Term (Safety Set) up to Approximately 30 Months
Deaths were collected and were considered to be an on treatment death up to 60 days post treatment.
Time frame: Baseline up to approximately 30 months
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