Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-label, Multicentre, Nonrandomized, Dose-escalating Phase I/II Study, With a Randomized Phase II Part, to Investigate the Safety and Tolerability of RO5072759 Given as Monotherapy in Patients With CD20+ Malignant Disease.
Brief Summary: The primary objective for the phase I part of the study is to investigate the safety and tolerability of escalating intravenous (IV) doses of obinutuzumab given as monotherapy in participants with CD20+ (tumor-infiltrating lymphocytic) Malignant Disease, including B-cell chronic lymphocytic leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL). The primary objective for the phase II part of the study is to investigate the efficacy and safety of one dose of obinutuzumab in participants with relapsed/refractory CLL and NHL that is, in turn, either indolent (iNHL) or aggressive (aNHL).

It is an open label dose escalating study in phase I and open label in phase II, but the two doses in iNHL \& aNHL are randomized (to high or low dose of the same open label treatment). CLL was not randomized as only one dose level was used.

Participants with a response who might gain additional benefit from being treated again in the opinion of the investigator may be enrolled in a Retreatment Period.


Options:
A: Inclusion Criteria:

* ECOG performance status of 0-1.
* Diagnosis of CLL or SLL that meets IWCLL 2008 criteria.
* Active disease meeting at least 1 of the IWCLL 2008 criteria for requiring treatment.
* Must have received at least one prior therapy for CLL/SLL.
* Considered not appropriate for treatment or retreatment with purine analog based therapy.
* Measurable nodal disease by CT.
* Patients must be able to receive outpatient treatment and laboratory monitoring at the institution that administers study drug for the entire study.

Exclusion Criteria:

* Known CNS lymphoma or leukemia.
* No documentation of cytogenetic and/or FISH in patient records prior to first dose of study drug.
* Any history of Richter's transformation or prolymphocytic leukemia.
* Uncontrolled Autoimmune Hemolytic Anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP).
* Prior exposure to ofatumumab or to ibrutinib.
* Prior autologous transplant within 6 months prior to first dose of study drug.
* Prior allogeneic stem cell transplant within 6 months or with any evidence of active graft versus host disease or requirement for immunosuppressants within 28 days prior to first dose of study drug.
* History of prior malignancy, with the exception of certain skin cancers and malignancies treated with curative intent and with no evidence of active disease for more than 3 years.
* Serologic status reflecting active hepatitis B or C infection.
* Unable to swallow capsules or disease significantly affecting gastrointestinal function.
* Uncontrolled active systemic fungal, bacterial, viral, or other infection.
* History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug.
* Requires anticoagulation with warfarin.
B: Inclusion Criteria:

1. Documented CLL requiring treatment (irrespective if first- or relapse treatment) according to International Working Group on CLL (iwCLL) criteria

   In case of previously treated patients, these must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods before start of the study treatment in the CLL2-BIO trial:
   * chemotherapy within ≥ 28 days
   * antibody treatment within ≥ 14 days
   * kinase inhibitors, Bcl-2-antagonists or immunomodulatory agents within ≥ 3 days
   * corticosteroids may be applied until the start of the BIO-regimen, these have to be reduced to an equivalent of ≤ 20 mg prednisolone during treatment
2. Adequate hematologic function as indicated by a platelet count ≥ 25 x 109/L, a neutrophil count ≥ 1,0 x 109/L and a hemoglobin value ≥ 8.0 g/dL, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration)
3. Adequate renal function as indicated by a creatinine clearance ≥ 30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hrs urine collection
4. Adequate liver function as indicated by a total bilirubin ≤ 2x, aspartate aminotransferase (AST)/ alanin aminotransferase (ALT) ≤ 2.5x the institutional upper limit of normal (ULN) value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome
5. Negative serological testing for hepatitis B, negative testing for hepatitis-C RNA and negative HIV antibody test within 6 weeks prior to registration
6. Age ≥ 18 years
7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2, ECOG 3 is only permitted if related to CLL (e.g. due to anemia or severe constitutional symptoms)
8. Life expectancy ≥ 6 months
9. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

1. Transformation of CLL (i.e. Richter's transformation, pro-lymphocytic leukemia)
2. Known central nervous system (CNS) involvement
3. Patients with confirmed progressive multifocal leukoencephalopathy (PML)
4. Malignancies other than CLL currently requiring systemic therapy
5. Uncontrolled infection requiring systemic treatment
6. Any comorbidity or organ system impairment rated with a cumulative illness rating scale (CIRS) score of 4, excluding the eyes/ears/nose/throat/larynx organ system or any other life- threatening illness, medical condition or organ system dysfunction that - in the investigator´s opinion - could compromise the patients safety or interfere with the absorption or metabolism of the study drugs (e.g, inability to swallow tablets or impaired resorption in the gastrointestinal tract)
7. Use of investigational agents which might interfere with the study drug within 3 days prior to Registration
8. Known hypersensitivity to ofatumumab, ibrutinib or any of the excipients Please note: Patients with a known hypersensitivity to bendamustine are allowed to participate but will not receive a debulking with bendamustine
9. Requirement of treatment with strong CYP3A4-inhibitors/-inducers or anticoagulant with phenprocoumon (marcumar), warfarin, or other vitamin k antagonists
10. History of stroke or intracranial hemorrhage within 6 months prior to registration
11. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment and monthly during debulking, induction and maintenance therapy)
12. Fertile men or women of childbearing potential unless:

    * surgically sterile or ≥ 2 years after the onset of menopause, or
    * willing to use two methods of reliable contraception including one highly effective (Pearl Index \< 1) and one additional effective (barrier) method during study treatment and for 12 months after end of study treatment.
13. Vaccination with a live vaccine ≤ 28 days prior to registration
14. Legal incapacity
15. Prisoners or subjects who are institutionalized by regulatory or court order
16. Persons who are in dependence to the sponsor or an investigator
C: Inclusion Criteria:

* Specific Diagnosis of B-Cell CLL
* An absolute lymphocytosis of \> 5,000/μL
* Morphologically, the lymphocytes must appear mature with \< 55% prolymphocytes
* Bone marrow examination must include at least a unilateral aspirate and biopsy; the aspirate smear must show \> 30% of all nucleated cells to be lymphoid or the bone marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement by CLL; the overall cellularity must be normocellular or hypercellular
* Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the absence of other pan-T-cell markers; additionally, the B-cells must be monoclonal with regard to expression of either κ or λ and have surface immunoglobulin expression of low density; patients with bright surface immunoglobulin levels must have CD23 co-expression
* Patients must be in the intermediate- or high-risk categories of the modified three-stage Rai staging system (i.e., stages I, II, III, or IV)
* Patients in the intermediate-risk group must have evidence of active disease as demonstrated by at least one of the following criteria:

  * Massive or progressive splenomegaly, hepatomegaly and/or lymphadenopathy;
  * Presence of weight loss \> 10% over the preceding 6 month period;
  * Grade 2 or 3 fatigue;
  * Fevers \> 100.5°F or night sweats for greater than 2 weeks without evidence of infection;
  * Progressive lymphocytosis with an increase of \> 50% over a 2 month period or an anticipated doubling time of less than 6 months
* No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL
* No medical condition requiring chronic use of oral corticosteroids
* Performance Status 0 - 2
* Due to alterations in host immunity, patients with HIV may not be enrolled
* Due to the unknown teratogenic potential of alemtuzumab, pregnant or nursing women may not be enrolled; women and men of reproductive potential should agree to use an effective means of birth control
* Creatinine =\< 1.5 x upper limit of institutional normal value
* Coomb's Testing NEGATIVE
D: Inclusion Criteria:

* Adult patients, \>=18 years of age;
* Phase 1 only: CD20+ malignant disease (B-cell lymphoma or B-CLL);
* Phase 2 only: relapsed or refractory indolent NHL, relapsed or refractory aggressive NHL or relapsed or refractory B-CLL
* Have a clinical indication for treatment as determined by the investigator
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* Life expectancy \>12 weeks

Exclusion Criteria:

* Prior use of any investigational antibody therapy or other agent within 6 months of study start;
* Prior use of any anti-cancer vaccine;
* Prior use of standard anti-lymphoma/leukemia therapy or radiation therapy within 4 weeks of enrollment;
* Prior use of MabThera (rituximab) within 8 weeks of study entry;
* Prior administration of radioimmunotherapy 3 months prior to study entry;
* Central nervous system (CNS) lymphoma.

Answer: D