Content - SAKK 35/14

SAKK 35/14 - Treatment of follicular lymphoma with rituximab and ibrutinib

Trial SAKK 35/14 is treating patients with advanced follicular lymphoma. A common sign of this type of cancer, which affects the immune cells, is enlargement of the lymph nodes. Many patients who are found to have follicular lymphoma do not display any symptoms at first, so immediate treatment is generally not needed. Once symptoms appear, patients begin chemotherapy supplemented by treatment with the antibody rituximab. When their chemotherapy is over, they continue to take rituximab as maintenance therapy. There are indications from clinical trials that supplementing rituximab with ibrutinib results in better outcomes. Trial SAKK 35/14 is setting out to investigate whether this is the case. In addition to their rituximab, participants will take one capsule of ibrutinib or placebo every day for 24 months.


Flyer

Study Chair:

Dr. Emanuele Zucca, IOSI, +41 91 811 91 47

  • Contacts at the hospitals

  • Inclusion criteria

    • 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* scanFDG-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

      • Platelets ≥ 100 x 109/L or ≥ 50 x 109/L if bone marrow involvement independent of transfusion support in either situation

    • Adequate hepatic function:

      • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN)

      • Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin

    • Adequate renal function:

      • Serum creatinine ≤ 2 x ULN and corrected calculated creatinine clearance ≥ 40 mL/min/1.73m2.

      • Women of childbearing potential have a negative serum (beta-human chorionic gonadotropin) or urine pregnancy test at Screening.

      • Patient compliance and geographic proximity allow proper staging and follow-up.

  • Exclusion criteria

    • 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 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

    • Women who are pregnant or breastfeeding

    • Patients regularly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to Prednisone ≤ 15 mg/day for indications other than lymphoma or lymphoma-related symptoms

Locations for this trial:

Hirslanden Klinik Aarau
Schänisweg
0 5001 Aarau
Kantonsspital Aarau
Tellstrasse 25
0 5001 Aarau
Kantonsspital Baden
Im Ergel 1
4600 Baden
St. Claraspital AG
Kleinriehenstrasse 30
0 4058 Basel
Universitätsspital Basel
Petersgraben 4
0 4031 Basel
Istituto Oncologico della Svizzera Italiana IOSI
Via Ospedale
0 6500 Bellinzona
Inselspital
Freiburgstrasse 8
3010 Bern
Spitalzentrum Oberwallis
Ueberlandstrasse 14
0 3902 Brig
Kantonsspital Bruderholz
-
0 4101 Bruderholz
Kantonsspital Graubünden
Loëstrasse 170
7000 Chur
Hôpitaux Universitaires de Genève HUG
Rue Gabrielle-Perret-Gentil 4
0 1205 Genève
Kantonsspital Liestal
Rheinstrasse 26
0 4410 Liestal
Kantonsspital Luzern
Spitalstrasse
0 6000 Luzern
Kantonsspital Olten
Baslerstrasse 150
0 4600 Olten
Hôpital du Valais Sion
Avenue du Grand-Champsec 80
0 1951 Sion
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen
Kantonsspital Winterthur
Brauerstrasse 15
0 8401 Winterthur
Klinik Hirslanden Zürich
Witellikerstrasse 40
0 8032 Zürich
Stadtspital Triemli
Birmensdorferstrasse 497
0 8063 Zürich
UniversitätsSpital Zürich
Rämistrasse 100
0 8091 Zürich