Content - SAKK 35/15

SAKK 35/15 - Safety and tolerability of a combination of obinutuzumab and venetoclax in patients with advanced follicular lymphoma

In this trial we are investigating the safety and tolerability of a combination of obinutuzumab and venetoclax in patients with advanced follicular lymphoma. B-cells are a subclass of white blood cells and therefore a constituent of blood (lymphocytes) and the immune system. Precursor cells of lymphocytes are derived from the bone marrow, and some of these cells ultimately mature in lymph nodes into antibody-producing B cells via various other precursor cells. Lymphomas form as a result of the degeneration and uncontrolled growth of B cells or B precursor cells during development. Follicular lymphoma occurs when precursor cells of B lymphocytes degenerate in lymph node follicles and replicate in an uncontrolled manner.

Obinutuzumab is a protein that detects and binds to receptors on the surface of B lymphocytes, causing them to die. Follicular lymphoma also involves the uncontrolled formation of the protein Bcl-2, which regulates cell death. Venetoclax inhibits this protein.

The combination of the two drugs has so far been tested in a small number of patients with follicular lymphoma. Laboratory data have shown that obinutuzumab and venetoclax can mutually potentiate their effects against various types of lymphoma, including follicular lymphoma. We believe that this combination will offer a more effective treatment for patients with follicular lymphoma.

Study Chair:

Dr. Anastasios Stathis, IOSI, +41 91 811 89 31

  • Contacts at the hospitals

  • Inclusion criteria

    • Written informed consent according to ICH/GCP regulations before registration.
    • Histological diagnosis of FL CD20+; grade 1, 2, 3a; stage III+IV; stage II not suitable for radiotherapy; all FLIPI
    • In need of first systemic therapy
    • At least one two-dimensionally measurable nodal lesion with a longest diameter (LDi) ˃15 mm or a measurable extra nodal lesion with a LDi ˃ 10 mm in CT, PET/CT scan (preferable) or MRI, according to Cheson et al, 2014
    • Bone marrow biopsy within 6 months.
    • Age18-80 years
    • WHO performance status 0-2
    • Adequate bone marrow function
    • Adequate hepatic function
    • Adequate renal function
    • Women of childbearing potential have a negative serum (beta-human chorionic gonadotropin [β-hCG]) pregnancy test within 3 days before inclusion into the trial.
  • Exclusion criteria

    • FL stage I

    • Known primary central nervous system (CNS) lymphoma

    • Known CNS or leptomeningeal involvement

    • Previous systemic FL therapies

    • History of other malignancy that could affect compliance with the protocol or interpretation of results

    • Concurrent treatment with other experimental drugs or other anticancer therapy in a clinical trial within 30 days prior to registration.

    • Live-virus vaccines treatment within 28 days prior to registration

    • Patients regularly taking corticosteroids during the last 30 days, unless administered at a dose equivalent to prednisone ≤ 15 mg/day for indications other than lymphoma or lymphoma-related symptoms

    • Women who are breastfeeding

    • Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV), unstable angina pectoris, history of myocardial infarction within the last six months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia), uncontrolled hypertension (sustained systolic blood pressure > 150 mm Hg and/or diastolic > 100 mm Hg despite antihypertensive therapy)

    • History of cerebrovascular accident or intracranial hemorrhage within 6 months prior to registration

    • Known history of

      • human immunodeficiency virus (HIV)

      • active/chronic Hepatitis C

      • active/chronic Hepatitis B Virus infection (HBsAg+ and/or HBcAb+)or

      • any active systemic infection requiring intravenous (iv) antimicrobial treatment.

    • Patients with a history of recurring or chronic infections may be included in the study but caution should be exercised and an infectious disease expert should be consulted before enrollment in the trial.

    • Requires anticoagulation with vitamin K antagonists (e.g. phenprocoumon, warfarin)

    • Coagulation parameters

      • INR ˃1.5x ULNPT or

      • PTT/aPTT ˃1.5x ULN

    • Requires treatment with strong CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) and strong CYP3A inducers (such as rifampin, carbamazepine, phenytoin, St. John's wort) 7 days prior to registration

    • Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information (if applicable) or most recent IB (if approved product information not available)

    • Known hypersensitivity to trial drugs or to any component of the trial drugs

    • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products

    • Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment, affect patient compliance or place the patient at high risk from treatment-related complications.

    • Psychiatric disorder precluding understanding information of trial-related topics, giving informed consent

Locations for this trial:

Universitätsspital Basel
Petersgraben 4
0 4031 Basel
Istituto Oncologico della Svizzera Italiana IOSI
Via Ospedale
0 6500 Bellinzona
Inselspital
Freiburgstrasse 8
3010 Bern
Kantonsspital Graubünden
Loëstrasse 170
7000 Chur
Hôpitaux Universitaires de Genève HUG
Rue Gabrielle-Perret-Gentil 4
0 1205 Genève
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen