Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Double-blind, Placebo-controlled Phase 3 Study of Ibrutinib, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Combination With Bendamustine and Rituximab (BR) in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Brief Summary: The purpose of this study is to examine the safety and efficacy of Ibrutinib administered in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).


Options:
A: Inclusion Criteria:

* Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets protocol-defined criteria
* Active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic Leukemia 2008 criteria for requiring treatment
* Measurable nodal disease by computed tomography
* Relapsed or refractory CLL or SLL following at least 1 prior line of systemic therapy consisting of at least 2 cycles of a chemotherapy-containing regimen
* Eastern Cooperative Oncology Group Performance Status score of 0 or 1
* Hematology and biochemical values within protocol-defined limits
* Agrees to protocol-defined use of effective contraception
* Women of childbearing potential must have negative blood or urine pregnancy test at screening

Exclusion Criteria:

* Recent therapeutic interventions within 3 (chemotherapy/radiotherapy) to 10 weeks (immunotherapy)
* Prior treatment with ibrutinib or other Bruton's tyrosine kinase inhibitors or prior randomization in any other clinical study evaluating ibrutinib
* The presence of deletion of the short arm of chromosome 17
* Patients previously treated with a bendamustine-containing regimen who did not achieve a response or who relapsed and required treatment within 24 months of treatment with that regimen
* Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant
* Received a hematopoietic stem cell transplant
* Known central nervous system leukemia/lymphoma or Richter's transformation
* Patients with uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
* Chronic use of corticosteroids
* History of prior malignancy, except: malignancy treated with curative intent and with no known active disease present for \>=3 years before randomization; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated cervical carcinoma in situ without evidence of disease
* History of stroke or intracranial hemorrhage within 6 months prior to randomization; or clinically significant cardiovascular disease
* Requires anticoagulation with warfarin or equivalent vitamin K antagonists or treatment with strong CYP3A4/5 inhibitors
* Known history of human immunodeficiency virus or hepatitis C, or active infection with hepatitis B or C
* Any uncontrolled active systemic infection or any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
* A woman who is pregnant or breast feeding, or a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug
B: 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.
C: Inclusion Criteria:

* Adults with documented diagnosis of active CLL requiring treatment
* Bulky lymphadenopathy, defined as at least 1 lymph node \>5 cm
* Must be refractory to fludarabine treatment
* Age 18 yrs or older
* At least 2 prior therapies for CLL
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Signed written informed consent

Exclusion Criteria:

* Prior allogeneic stem cell transplant at any time, or autologous stem cell transplant within 6 months
* Treatment with any unapproved drug substance or experimental therapy within 4 weeks, or currently participating in another interventional clinical study
* CLL transformation, prolymphocytic leukemia, or central nervous system (CNS) involvement of CLL
* Active autoimmune hemolytic anemia (AIHA) requiring treatment except if associated with progressive disease requiring anti-CLL treatment
* Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
* Human immunodeficiency virus (HIV) positive
* Significant concurrent, uncontrolled medical condition
* Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry
* Non-protocol corticosteroid usage except a maintenance dose corresponding to less than or equal to 10 mg prednisone
* Abnormal lab values: Creatinine \> 2.0 times upper normal limit (unless normal creatinine clearance), or total bilirubin \> 2.0 times upper normal limit (unless due to liver involvement of CLL or due to Gilbert's syndrome), or alanine transaminase (ALT) \> 2.5 times upper normal limit (unless due to liver involvement of CLL)
* Known or suspected hypersensitivity to ofatumumab
* Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception
D: Inclusion Criteria:

* documented chronic lymphocytic leukemia (CLL) requiring treatment according to International Working Group on CLL (iwCLL) criteria
* adequate hematologic function: platelets ≥ 25.000/µl, neutrophils ≥ 1.000/µl and hemoglobin ≥8.0 g/dL, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration)
* adequate renal function: a creatinine clearance ≥30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hr. urine collection
* adequate liver function: total bilirubin ≤1,5x, 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
* negative serological testing for hepatitis B, negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
* age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2, ECOG 3 is only permitted if related to CLL
* life expectancy ≥ 6 months
* ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

* transformation of CLL (i.e. Richter's transformation, prolymphocytic leukemia)
* known central nervous system (CNS) involvement
* confirmed progressive multifocal leukoencephalopathy (PML)
* malignancies other than CLL currently requiring systemic therapies
* uncontrolled infection requiring systemic treatment
* 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)
* ongoing inflammatory bowel disease
* ongoing drug induced pneumonitis
* use of investigational agents which would interfere with the study drug ≤28 days prior to registration
* known hypersensitivity to GA101 (obinutuzumab), CAL-101 (idelalisib) or any of the excipients
* pregnant women and nursing mothers
* 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 18 months after end of study treatment
* vaccination with a live vaccine ≤28 days prior to registration
* legal incapacity
* prisoners or subjects who are institutionalized by regulatory or court order
* persons who are in dependence to the sponsor or an investigator

Answer: A