Please select the eligibility criteria that correspond to the clinical trial below.
Title: Single-agent Rituximab as Maintenance Treatment Versus Observation After Combined Induction Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab in Patients Older Than 65 Years With Previously Untreated Chronic Lymphocytic Leukemia: a Phase III Trial of FILO
Brief Summary: RATIONALE: Classical chemotherapy does not cure advanced chronic lymphocytic leukemia (CLL) despite new drugs. Rituximab is a monoclonal antibody directed against CD20 surface antigen on B lymphocytes and leads to apoptosis of CD20 positive B lymphocytes. The highest response rate yet published in the treatment of first-line CLL has been obtained by the association of fludarabine, cyclophosphamide and rituximab (FCR). Now, the question is whether this response can be improved, as some trials showed that eradication of minimal residual disease (MRD) in CLL is associated with a longer treatment-free and overall survival. Maintenance therapy using rituximab has been recently approved as a means of prolonging remission in patients with indolent non Hodgkin's lymphoma. Maintenance therapy with rituximab could be of interest in treatment of MRD in CLL and prolonging remission and survival times.

PURPOSE: The overall purpose of the study is to determine the value of immunotherapy maintenance with single agent rituximab in comparison with no further treatment (observation ) for previously untreated chronic lymphocytic leukaemia in elderly (\>65 years) patients who respond to induction immunochemotherapy with FCR.


Options:
A: Inclusion criteria

* B-CLL
* Matutes score 4 or 5
* Binet stages B or C
* Age \> 65 years old
* No previous treatment of CLL by chemotherapy, radiotherapy or immunotherapy, except glucocorticoids \< 1 month
* Patient's written informed consent
* Life expectancy \> 6 months

Exclusion criteria

* Binet stage A
* ECOG performance status 2 or more
* Presence of a 17p deletion by FISH (\> 10% positive cores)
* Clinically significant auto-immune cytopenia, Coombs-positive hemolytic anemia as judged by the treating physician
* Patients with a history of another malignancy in complete remission less than 5 years, except basal cell skin cancer or tumor treated curatively by surgery
* Concomitant disease requiring prolonged use of corticosteroids (\> 1 month)
* Any severe co-morbidities such as NYHA Class III or IV heart failure, myocardial infarction within 6 months, unstable angina, ventricular tachyarrhythmias requiring ongoing treatment, severe uncontrolled myocardiopathy, uncontrolled hypertension, severe chronic obstructive pulmonary disease with hypoxemia, or uncontrolled diabetes mellitus.
* CIRS (Cumulative Illness rating Scale) \> 6
* Known hypersensitivity to murine proteins or to any of the study drugs or to their components
* Transformation into an aggressive B-cell malignancy (e.g. diffuse large cell lymphoma, Hodgkin lymphoma) or prolymphocytic leukemia
* Active bacterial, viral or fungal infection
* Seropositivity HIV, hepatitis C or hepatitis B (unless clearly due to vaccination)
* Total bilirubin, alkaline phosphatases and aminotransferases \> 2 x ULN
* Creatinine clearance \< 60 ml/min calculated according to the formula of Cockcroft and Gault
* Any coexisting medical or psychological condition that would preclude participation to the required study procedures
* Patient with mental deficiency preventing proper understanding of the requirements of treatment

Inclusion criteria at randomization

* Patients having received the full induction phase with 4 FC and 6 rituximab courses (with/without dose adjustments as per protocol)
* Complete or partial response according to NCI and iwCLL criteria at the end of induction phase
* Recovery from FCR toxicities
* Patient willingness to continue on protocol
B: Key Inclusion Criteria:

* Previously treated recurrent CLL
* Measurable lymphadenopathy
* Requires therapy for CLL
* Has experienced CLL progression \< 36 months since the completion of the last prior therapy

Key Exclusion Criteria:

* Recent history of a major non-CLL malignancy
* Evidence of an ongoing infection
* CLL refractory to bendamustine
* Concurrent participation in another therapeutic clinical trial

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
C: Inclusion Criteria:

* Chronic Lymphocytic Leukemia
* Circulating lymphocytes above a specific level
* Circulating lymphocytes showing certain markers

Exclusion Criteria:

* Previous treatment with rituximab or alemtuzumab within 6 months prior to enrollment in study.
* Previous stem cell transplantation.
* Received any of the following treatments within 4 weeks prior to entering this trial: A) Anti-cancer therapy, B) Glucocorticoids unless less than 10 mg per day, C) Radiotherapy.
* HIV positivity.
* Hepatitis B or hepatitis C.
* Other cancerous diseases, except certain skin cancers and cervix cancer.
* Certain serious medical conditions, including kidney or liver disease, some psychiatric illnesses, and stomach, heart, hormonal, nerve or blood diseases.
* Participation in another trial with a different new drug 4 weeks prior to enrollment in study.
* Current participation in any other clinical study.
* Pregnant or breast-feeding women.
* Women of childbearing age who are unable or unwilling to use adequate contraception.
D: 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.

Answer: A