Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II Study of Fludarabine + Rituximab Induction Followed by Alemtuzumab (Campath-1H, NSC #715969, IND #10864) Administered Subcutaneously as Consolidation in Untreated Patients With B-Cell Chronic Lymphocytic Leukemia
Brief Summary: This phase II trial is studying how well giving fludarabine together with rituximab followed by alemtuzumab works in treating patients with chronic lymphocytic leukemia. Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others can find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving fludarabine together with rituximab followed by alemtuzumab may kill more cancer cells.


Options:
A: 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.
B: Inclusion:

* Adult subjects with previously treated recurrent CLL who have measurable lymphadenopathy
* Require therapy for CLL
* Have experienced CLL progression \< 24 months since the completion of the last prior therapy
* Currently not sufficiently fit to receive cytotoxic therapy because of chemotherapy-induced bone marrow damage or comorbidities.
C: 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
D: 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

Answer: D