Rituximab With or Without Ibrutinib for Patients With Advanced Follicular Lymphoma

NCT02451111 | Terminated Phase 2 DMC

• 3 other identifiers: SAKK 35/142015-001487-19SNCTP000001327
• Study Type: interventional
• Target: 190
• Locations: 6 countries
• Sites: 42

Brief Summary

Follicular lymphomas FL has been traditionally approached either by an initial watch and wait policy in the asymptomatic patient, or with single agent treatments with the purpose of maintaining a good quality of life for a prolonged time.The combination of rituximab and ibrutinib has been tested in clinical trials and appeared to be well tolerated and active. Since ibrutinib seems to achieve better results when administered for prolonged time as shown in CLL, the investigators have chosen to compare its combination with rituximab to the prolonged rituximab-only schedule that was already shown to be very active in the SAKK 35/03 trial. The aim of the study is to investigate the efficacy, safety and tolerability of the treatment combination of Ibrutinib and Rituximab for patients with advanced follicular lymphoma in need of therapy.

Conditions

Follicular Lymphoma

Keywords

Rituximab; Ibrutinib; Follicular Lymphoma

Outcome Measures

Primary Outcomes (1)

• CR at 24 months determined by PET/CT scan by the IRR panel

  The evaluation of CR is outlined according to Cheson Criteria.. Any assessment within a window of week 102 to week 118 (inclusive) will be considered as the 24 months response assessment for determining the CR status. In addition, the CR status will be determined as follows for these specific cases:

  at 24 months

Secondary Outcomes (8)

• CR at 30 months determined by PET/CT scan by the IRR panel

  at 30 months

• MRD evaluation

  baseline and week 106

• Overall response (OR)

  at 24 weeks

• Duration of complete response (DUR)

  at 12 or 24 weeks or thereafter

• Progression-free survival (PFS) (PFS)

  at 12 or 24 weeks or thereafter

Study Arms (2)

Rituximab/Ibrutinib

ACTIVE COMPARATOR

Ibrutinib capsules for 24 months (104 weeks) daily (always at the same time) in a dose of 560 mg (4 x 140 mg capsules)

Drug: Ibrutinib; Drug: Rituximab

Rituximab/Placebo

PLACEBO COMPARATOR

Placebo as comparator for 24 months (4 capsules daily always at the same time)

Drug: Rituximab

Interventions

Ibrutinib DRUG

Patients will be instructed by the Investigator to take the amount of 560 mg Ibrutinib/Placebo (4 x 140 mg capsules) orally once daily with a glass of water at approximately the same time every day.

Also known as: Imbruvica®

Rituximab/Ibrutinib

Rituximab DRUG

Rituximab 375 mg/m2 has to be administered i.v. for the first four (4) infusions in all patients. After i.v. administration of Rituximab for the induction therapy, the administration mode can be changed to s.c. (1400 mg) in the maintenance phase dependent on the local standard of care.

Also known as: MabThera®

Rituximab/Ibrutinib; Rituximab/Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent according to ICH/GCP guidelines
• Histologically confirmed FL CD20+; grade 1, 2, 3a; stage III+IV; stage II not suitable for radiotherapy; all FLIPI
• Tumor specimens (slides or block) available for pathological review
• In need of systemic therapy (at least one of the following indications must be fulfilled):
• Symptomatic disease
• Bulky disease (≥ 6 cm)
• Steady, clinically significant progression over at least 3 months of any tumor lesion
• B-symptoms (weight loss \> 10% in 6 months, drenching night sweats, fever \> 38°C not due to infection)
• Anemia (hemoglobin \< 100 g/L) or thrombocytopenia (platelets 50-100 x 109/L) due to lymphoma
• At least one two-dimensionally measurable lesion with a longest diameter (LDi) ≥ 15 mm in contrast-enhanced 18F-FDG PET/CT\* scan
• FDG-avid tumor lesion in contrast-enhanced 18F-FDG PET/CT\* scan
• Age 18-85 years
• WHO performance status 0-2
• Adequate bone marrow function:
• Absolute neutrophil count (ANC) \> 1.0 x 109/L independent of growth factor support

You may not qualify if:

• Tumor bulk requiring fast response
• Known central nervous system lymphoma
• Previous systemic FL therapies
• Major surgery 4 weeks prior to randomization
• Previous or concomitant malignancy diagnosed within 3 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
• History of stroke or intracranial hemorrhage within 6 months prior to randomization
• Clinically significant cardiovascular diseases such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (i.v.) antibiotics
• Concomitant diseases that require anticoagulation with warfarin or equivalent vitamin K antagonists (eg. phenprocoumon), factor Xa inhibitors (e.g. rivaroxaban, apixaban), direct thrombin inhibitors (e.g. dabigatran) or platelet inhibitors/antiplatelet agents. Aspirin is allowed (up to 300 mg/d).
• Concomitant diseases that require treatment with strong or moderate CYP3A inhibitors (see http://medicine.iupui.edu/clinpharm/ddis/clinical-table/)
• Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information or known hypersensitivity to trial drugs
• Concurrent treatment with other experimental drugs or other anticancer therapy, treatment in a clinical trial within 30 days prior to trial entry
• Vaccinated with live, attenuated vaccines 4 weeks prior to randomization
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of Ibrutinib capsules, or put the study outcomes at undue risk
• Psychiatric disorder precluding understanding information of trial related topics, giving informed consent or interfering with compliance for oral drug intake

Sponsors & Collaborators

• Swiss Cancer Institute: lead
• Nordic Lymphoma Group: collaborator

Study Sites (42)

Akademisches Lehrkrankenhaus Feldkirch

Feldkirch, 6800, Austria

Location

Aalborg Universitetshospital

Aalborg, 9000, Denmark

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Odense Universitetshospital

Odense C, 5000, Denmark

Location

Helsinki University Hospital

Helsinki, 00029 HUS, Finland

Location

Kuopio University Hospital

Kuopio, 70029, Finland

Location

University Hospital Tampere Radius

Tampere, 33521, Finland

Location

Turku University Hospital

Turku, 20520, Finland

Location

Haukeland University Hospital

Bergen, 5021, Norway

Location

Oslo University Hospital

Oslo, 424, Norway

Location

Stavanger University Hospital

Stavanger, 4011, Norway

Location

Universitetssykehuset i Nord-Norge

Tromsø, 9038, Norway

Location

Sunderby Hospital

Luleå, 971 80, Sweden

Location

Skanes Universitetssjukhus

Lund, 221 85, Sweden

Location

Örebro University Hospital

Örebro, 701 85, Sweden

Location

Karolinska University Hospital

Solna, 17165, Sweden

Location

Karolinska University Hospital

Stockholm, 141 86, Sweden

Location

University Hospital of Umeå

Umeå, 901 85, Sweden

Location

Hirslanden Klinik Aarau

Aarau, CH-5001, Switzerland

Location

Kantonspital Aarau

Aarau, CH-5001, Switzerland

Location

Zuger Kantonsspital

Baar, 6340, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

St. Claraspital AG

Basel, CH-4016, Switzerland

Location

Universitaetsspital Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital, Bern

Bern, CH-3010, Switzerland

Location

Spitalzentrum Oberwallis - Brig

Brig, 3900, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, CH-4101, Switzerland

Location

Hopitaux Universitaires de Geneve

Geneva, 1211, Switzerland

Location

Centre de Chimiothérapie Anti-Cancéreuse SA (CCAC)

Lausanne, 1004, Switzerland

Location

Kantonsspital Baselland

Liestal, 4410, Switzerland

Location

Kantonsspital Luzern

Luzerne, CH-6000, Switzerland

Location

Spital Thurgau (Kantonsspital Münserlingen und Frauenfeld)

Münsterlingen, 8596, Switzerland

Location

Kantonsspital Olten

Olten, CH-4600, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Hôpital du Valais - CHCVR

Sion, 1951, Switzerland

Location

Spital STS AG

Thun, CH-3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Stadtspital Triemli

Zurich, 8063, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Onkozentrum Hirslanden

Zurich, CH-8032, Switzerland

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

ibrutinib; 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

Study Officials

• Emanuele Zucca, Prof

  Oncology Institute of Southern Switzerland IOSI, Bellinzona

  STUDY CHAIR

• Bjørn Østenstad, MD

  Oslo University Hospital

  STUDY CHAIR

• Björn Wahlin, MD

  Karolinska University Hospital, Stockholm

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2015
• First Posted: May 21, 2015
• Study Start: November 6, 2015
• Primary Completion: December 1, 2022
• Study Completion: July 15, 2023
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); NO (4); DK (4); FI (4); SE (6); CH (23)