Phase-I-Studie mit Obinutuzumab in Kombination mit Venetoclax bei bisher unbehandelten Patienten mit follikulärem Lymphom

Drug: Obinutuzumab;Drug: Venetoclax

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 [ß-hCG]) pregnancy test within 3 days before inclusion into the trial.

Exclusion Criteria:

- FL stage I

- Transformation to high-grade DLBCL prior to therapy

- FL grade 3 b

- Indolent lymphoma other than FL

- 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 ULN

- PT 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