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Pharmacokinetics and Pharmacodynamics of BI 695500 vs. Rituximab as First Line-treatment in Patients With Low Tumor Burden Follicular Lymphoma

Phase 1
Completed
Conditions
Lymphoma, Follicular
Interventions
Drug: BI 695500
Drug: MabThera
Registration Number
NCT01950273
Lead Sponsor
Boehringer Ingelheim
Brief Summary

The primary objective of the study is to assess the pharmacokinetic (PK) similarity of Boehringer Ingelheim (BI) 695500 vs. rituximab (MabThera®) in previously untreated patients with low tumor burden follicular lymphoma (LTBFL).

The secondary objective of the study is to evaluate the pharmacodynamics (PD), safety, and anti-tumor activity of BI 695500 vs. rituximab (MabThera®), as well as the presence of anti-drug antibodies (ADAs).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
95
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
BI695500BI 695500BI695500, once a week for 4 weeks (4 administrations in total)
MabTheraMabTheraMabThera, once a week for 4 weeks (4 administration in total)
Primary Outcome Measures
NameTimeMethod
Area Under the Concentration (AUC) Time Curve of BI 695500 and Rituximab (MabThera®) Over the First Dosing Interval (Pre-infusion on Day 1 to Pre-infusion on Day 8)Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 1, and at 24, 48, 72, 96 and 168 hours from start of infusion 1.

This outcome measure presents area under the concentration time curve of BI 695500 and Rituximab (MabThera®) over the first dosing interval (pre-infusion on Day 1 to pre-infusion on Day 8) (AUCDay 1-Day 8) for assessment of PK (Pharmacokinetics) similarity.

Secondary Outcome Measures
NameTimeMethod
Maximum Measured Concentration of Rituximab (MabThera®) and BI 695500 in Plasma (Cmax) Following Dose 4Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 4, and at 24, 48, 72, 96, 168, 336, 672, 1344, 2016 and 2880 hours from start of infusion 4.

This outcome measure presents maximum measured concentration of Rituximab (MabThera®) and BI 695500 in plasma (Cmax) following Dose 4.

Area Under the Depletion-time Curve of the Cluster of Differentiation (CD)19+ B-cell Count (% Change From Baseline (CFB)) in Peripheral Blood From Pre-infusion on Day 1 Until Last Measurement on Day 8 (Pre-infusion)Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion, and at 24, 48, 72, 96 and 168 hours from start of infusion.

This outcome measure presents area under the depletion-time curve of the CD19+ B-cell count (% change from baseline) in peripheral blood from pre-infusion on Day 1 until last measurement on Day 8 (pre-infusion) (AUC Day 1-Day 8, CD19+).

Change From Baseline (%) of CD19+ B-cells in Peripheral Blood Measured After Seven Days on Day 8 (Day 8 Pre-infusion Time Point)Blood sampling was done at 168 hours from start of infusion.

This outcome measure presents percent change from baseline of CD19+ B-cells in peripheral blood, measured after 7 days (i.e., Day 8 pre-infusion time point) (PCFBpre,2 CD19+).

AUC of BI 695500 and Rituximab (MabThera®) Over the Fourth Dosing Interval (Pre-infusion on Day 22 to Day 29) (AUC Day 22-Day 29)Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 4, and at 24, 48, 72, 96 and 168 hours from start of infusion 4.

This outcome measure presents area under the concentration of BI 695500 and Rituximab (MabThera®) over the fourth dosing interval (pre-infusion on Day 22 to Day 29).

Maximum Measured Concentration of BI 695500 and Rituximab (MabThera®) in Plasma (Cmax) Following Dose 1Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 1, and at 24, 48, 72, 96 and 168 hours from start of infusion 1.

This outcome measure presents maximum measured concentration of BI 695500 and Rituximab (MabThera®) in plasma (Cmax) following Dose 1

Overall Response Rate (ORR) (Complete Response (CR) Plus Partial Response (PR)) Evaluated Approximately One Month After Last Dose of BI 695500 or Rituximab (MabThera®)at Day 50.

Overall Response Rate (ORR) comprised Complete Response (CR) plus Partial Response (PR) evaluated approximately one month after last dose of BI 695500 or Rituximab \[MabThera®\]. Overall Response as defined by the revised International Working Group (IWG) Criteria 2007, using the Investigator's assessment.

Percentage of Patients With Treatment Emergent Adverse Events (TEAEs) Selected for Comparability Assessment of BI 695500 and Rituximab (MabThera®)Adverse Events (AEs) that started or worsened on or after the first dose of study medication and prior to the last date of study medication + 4 months (120 days) inclusive.

This outcome measure presents percentage of patients with Treatment Emergent Adverse Events (TEAEs) selected for comparability assessment of BI 695500 and Rituximab (MabThera®).

Trial Locations

Locations (29)

UZ Leuven

🇧🇪

Leuven, Belgium

Haemato-Onkologie Hamburg

🇩🇪

Hamburg, Germany

Klinikum Kassel GmbH

🇩🇪

Kassel, Germany

Auckland Clinical Studies Ltd

🇳🇿

Auckland, New Zealand

The Canberra Hospital

🇦🇺

Canberra, Migration Data, Australia

Brussels - UNIV St-Luc

🇧🇪

Bruxelles, Belgium

St. Petersburg GUZ City Clinical Oncology Dispensary

🇷🇺

St. Petersburg, Russian Federation

Hospital Virgen del Rocío

🇪🇸

Sevilla, Spain

HOP Haut-Lévêque

🇫🇷

Pessac, France

Namur - HOSP Ste-Elisabeth

🇧🇪

Namur, Belgium

Universitätsklinikum Freiburg

🇩🇪

Freiburg, Germany

Semmelweis University, 1st Dept. Internal Medicine

🇭🇺

Budapest, Hungary

University Hospital Brno

🇨🇿

Brno, Czechia

AKH - Medical University of Vienna

🇦🇹

Wien, Austria

Clinical Hospital Centre Zagreb

🇭🇷

Zagreb, Croatia

INS Bergonié

🇫🇷

Bordeaux cedex, France

HOP Morvan

🇫🇷

Brest, France

University Hospital Ostrava

🇨🇿

Ostrava-Poruba, Czechia

Centre Hospitalier Départemental Les Oudairies

🇫🇷

La Roche sur Yon, France

Hôpital la Milétrie - CHU Poitiers

🇫🇷

Poitiers, France

Gesundheitszentrum Wetterau gGmbH

🇩🇪

Bad Nauheim, Germany

Universitätsklinikum Carl Gustav Carus Dresden

🇩🇪

Dresden, Germany

Vseobecna fakultni nemocnice V Praze

🇨🇿

Praha 2, Czechia

Hospital Puerta del Mar

🇪🇸

Cádiz, Spain

General Hospital of Athens "G. Gennimatas"

🇬🇷

Athens, Greece

Oncol Centre M Sklodowska-Curie, Dept of Lung & Chest Cancer

🇵🇱

Warszawa, Poland

BHI of Omsk region - Clinical Oncology Dispensary

🇷🇺

Omsk, Russian Federation

Fundación Jiménez Díaz

🇪🇸

Madrid, Spain

Hospital Germans Trias i Pujol

🇪🇸

Badalona, Spain

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