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

NCT01950273 | Completed Phase 1 Results

• 2 other identifiers: 1301.52013-001904-12
• Study Type: interventional
• Target: 95
• Locations: 12 countries
• Sites: 28

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).

Conditions

Lymphoma, Follicular

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

  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.

Secondary Outcomes (7)

• 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.

• Maximum Measured Concentration of BI 695500 and Rituximab (MabThera®) in Plasma (Cmax) Following Dose 1

  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.

• Maximum Measured Concentration of Rituximab (MabThera®) and BI 695500 in Plasma (Cmax) Following Dose 4

  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, 168, 336, 672, 1344, 2016 and 2880 hours from start of infusion 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.

• 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.

Study Arms (2)

BI695500

EXPERIMENTAL

BI695500, once a week for 4 weeks (4 administrations in total)

Drug: BI 695500

MabThera

ACTIVE COMPARATOR

MabThera, once a week for 4 weeks (4 administration in total)

Drug: MabThera

Interventions

BI 695500 DRUG

BI695500, once a week for 4 weeks (4 administrations in total)

BI695500

MabThera DRUG

MabThera, once a week for 4 weeks (4 administrations in total)

MabThera

Eligibility Criteria

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

You may qualify if:

• Must give written informed consent and be willing to follow this Clinical Trial Protocol.
• Male or female patients, at least 18 years of age at Screening.
• Histologically-confirmed, stage II - IV Non-Hodgkin's lymphoma (CD20+ FL of Grades 1, 2, or 3a).
• Low tumor burden according to the Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria - no nodal or extranodal involvement of more than 7 cm, no more than 3 nodal sites with a diameter \>3 cm, no B symptoms (i.e., fever \>38°C, weight loss - unexplained loss of \>10 % body weight over the past 6 months, and sweats - the presence of drenching night sweats), no significant splenomegaly, no significant serious effusion, no complications such as organ compression, and less than 5x10\^9/L circulating tumor cells.
• Availability of archived tumor sample prior to screening.
• Patients not previously treated for their FL.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have at least 1 measurable lesion as per the International Working Group (IWG) criteria 2007 at Screening (lesion clearly measurable in at least 2 perpendicular dimensions; see Appendix 10.1 for further details).
• Adequate hematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) within 28 days prior to randomization, including:
• \- hemoglobin =9.0 g/dL (=5.6 mmol/L).
• \- absolute neutrophil count =1.5 × 10\^9/L.
• \- platelet count =100 × 10\^9/L.
• Adequate renal and liver function:
• \- serum creatinine \<2.0 mg/dL (\<176.8 micromol/L).
• \- total bilirubin \<2.0 mg/dL (\<34 mcmol/L) except for patient with Gilbert's Syndrome or Hemolysis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3 x upper limit of normal (ULN) (\<5 x ULN is acceptable if abnormalities are thought to be related to hepatic infiltration by FL).

You may not qualify if:

• Transformation to high-grade lymphoma (secondary to low-grade lymphoma).
• Presence or history of central nervous system lymphoma.
• Patients receiving current treatment with corticosteroids must not be receiving a dose exceeding 20 mg/day prednisone or equivalent.
• Patients with prior or concomitant malignancies within 5 years prior to screening except non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix, adequately treated breast cancer in situ, localized prostate cancer stage T1c - provided that the patient underwent curative treatment, and remains relapse free.
• Major surgery (excluding lymph node biopsy) within 28 days prior to randomization.
• Active, chronic or persistent infection that might worsen with immunosuppressive treatment (e.g., Human Immunodeficiency Virus \[HIV\], Hepatitis C Virus \[HCV\], Herpes Zoster); positive for HIV or tuberculosis at Screening.
• Patients with serological evidence of Hepatitis B virus (HBV) infection. Patients seropositive because of HBV vaccine are eligible. HBV positive patients may participate following consultation with a hepatitis expert regarding monitoring and use of HBV antiviral therapy, and provided they agree to receive treatment as indicated.
• Serious underlying medical conditions, which, per the investigator's discretion, could impair the ability of the patient to participate in the trial (including but not limited to ongoing active infection, severe immunosuppression, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease); patients who have significant cardiac disease, including but not limited to congestive heart failure of Class III or IV of the NYHA classification; uncontrolled angina or arrhythmia; any uncontrolled or severe cardiovascular or cerebrovascular disease.
• Known hypersensitivity or allergy to murine products.
• History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the trial drug.
• Receipt of a live/attenuated vaccine within 12 weeks prior to the Screening Visit.
• Prior treatment with BI 695500 and/or rituximab.
• Patients who received any prior therapy using monoclonal antibodies will be excluded; this does not apply to other biological drugs such as growth factors or anticoagulants.
• Treatment within a clinical trial within 4 weeks prior to initiation of trial treatment. Patients who have received treatment with a drug that has not received regulatory approval for any indication within 4 weeks or a minimum of 5 half-lives, whichever is longer, of the initial dose of trial medication.
• Any other co-existing medical or psychological condition(s) that will preclude participation in the trial or compromise ability to give informed consent and/or comply with study procedures.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (29)

The Canberra Hospital

Canberra, Migration Data, 2605, Australia

Location

AKH - Medical University of Vienna

Vienna, 1090, Austria

Location

Brussels - UNIV St-Luc

Brussels, 1200, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Namur - HOSP Ste-Elisabeth

Namur, 5000, Belgium

Location

Clinical Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

University Hospital Brno

Brno, 625 00, Czechia

Location

University Hospital Ostrava

Ostrava-Poruba, 70852, Czechia

Location

Vseobecna fakultni nemocnice V Praze

Prague, 128 08, Czechia

Location

INS Bergonié

Bordeaux, 33076, France

Location

HOP Morvan

Brest, 29609, France

Location

Centre Hospitalier Départemental Les Oudairies

La Roche-sur-Yon, 85025, France

Location

HOP Haut-Lévêque

Pessac, 33600, France

Location

Hôpital la Milétrie - CHU Poitiers

Poitiers, 86021, France

Location

Gesundheitszentrum Wetterau gGmbH

Bad Nauheim, 61231, Germany

Location

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Haemato-Onkologie Hamburg

Hamburg, 21075, Germany

Location

Klinikum Kassel GmbH

Kassel, 34125, Germany

Location

General Hospital of Athens "G. Gennimatas"

Athens, 11527, Greece

Location

Semmelweis University, 1st Dept. Internal Medicine

Budapest, 1083, Hungary

Location

Auckland Clinical Studies Ltd

Auckland, 1010, New Zealand

Location

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

Warsaw, 02-781, Poland

Location

BHI of Omsk region - Clinical Oncology Dispensary

Omsk, 644013, Russia

Location

St. Petersburg GUZ City Clinical Oncology Dispensary

Saint Petersburg, 198255, Russia

Location

Hospital Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital Puerta del Mar

Cadiz, 11009, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; 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

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2013
• First Posted: September 25, 2013
• Study Start: September 27, 2013
• Primary Completion: December 22, 2015
• Study Completion: December 22, 2015
• Last Updated: September 5, 2018
• Results First Posted: September 5, 2018

Record last verified: 2018-08

Locations

GR (1); HU (1); CR (1); DE (5); PL (1); CZ (3); AU (1); NZ (1); RU (2); ES (4); FR (5); BE (3)