Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Single-arm, International, Multi-center Trial Investigating the Efficacy and Safety of Ofatumumab Retreatment and Maintenance in CLL Patients Who Progressed Following Response or Stable Disease After Ofatumumab Treatment in Hx-CD20-406
Brief Summary: The purpose of the trial is to investigate the efficacy and safety of ofatumumab retreatment and maintenance in patients with chronic lymphocytic leukemia who have previously responded or had disease stabilization after ofatumumab in an ongoing trial (Hx-CD20-406).


Options:
A: Inclusion Criteria:

1. FOR TREATMENT-NAIVE GROUP ONLY: Men and women ≥ 65 years of age with confirmed diagnosis of CLL/SLL, who require treatment per NCI or International Working Group guidelines 15-18
2. FOR RELAPSED/REFRACTORY GROUP ONLY: Men and women ≥ 18 years of age with a confirmed diagnosis of relapsed/refractory CLL/SLL following previous therapy(ie, failed ≥ 2 previous treatments for CLL/SLL and at least 1 regimen had to have had a purine analog \[eg, fludarabine\] for subjects with CLL)
3. FOR HIGH-RISK RELAPSED/ REFRACTORYGROUP ONLY: Men and women ≥ 18 years of age with a confirmed diagnosis of relapsed/refractory CLL/SLL with suboptimal response to chemoimmunotherapy, defined as progression of disease within 24 months of initiation of a regimen containing at least a nucleoside analogue or bendamustine in combination with a monoclonal antibody or failure to respond to such a regimen. (Note: a minimum of 2 cycles of chemoimmunotherapy required for eligibility)
4. ECOG performance status of ≤ 2
5. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty

Exclusion Criteria:

1. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least 2 years or which will not limit survival to \< 2 years
2. Any immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 4 weeks before first dose of study drug (corticosteroids for disease-related symptoms allowed but require 1-week washout before study drug administration)
3. Central nervous system (CNS) involvement by lymphoma
4. Major surgery within 4 weeks before first dose of study drug
5. Concomitant use of medicines known to cause QT prolongation or torsades de pointes
6. Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, and QTc \> 470 msec
7. Lactating or pregnant
B: Inclusion Criteria:

1. 1.Patients must have a diagnosis of high-risk CLL/SLL and be previously treated with up to 3 lines of prior therapy. High-risk CLL and high-risk SLL is defined by the presence of a 17p deletion or 11q deletion or TP53 mutation. Any CLL and SLL patient who has a short remission duration of less than 3 years after prior first-line chemo-immunotherapy, such as the FCR regimen, also fulfills criteria of high-risk CLL/SLL, regardless of the presence or absence of cytogenetic abnormalities.
2. 2.CLL and SLL patients with 17p deletion or TP53 mutation will not be required to have received any prior therapy, given the poor outcome of CLL/SLL patients to standard frontline chemo-immunotherapy, such patients will be eligible if they are untreated or if they have received up to 3 lines of prior therapy.
3. Patients must have an indication for treatment by 2008 IWCLL Criteria.
4. Patients age \> 18 years at the time of signing informed consent. Understand and voluntarily sign an informed consent. Be able to comply with study procedures and follow-up examinations.
5. Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 0-1.
6. Patients of childbearing potential must be willing to practice highly effective birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], sexual abstinence, or sterilized partner) during the study and for 30 days after the last dose of study drug. Women of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as follows: Amenorrhea \>/= 12 consecutive months without another cause and a documented serum follicle stimulating hormone (FSH) level \>35 mIU/mL; a male of childbearing potential is any male that has not been surgically sterilized.
7. Adequate renal and hepatic function as indicated by all of the following: Total bilirubin \</=1.5 x institutional Upper Limit of Normal (ULN) except for patients with bilirubin elevation due to Gilbert's disease who will be allowed to participate; an Alanine (ALT) \</=2.5 x ULN; and an estimated creatinine clearance (CrCl) of \> 30 mL/min, as calculated by the Cockcroft-Gault equation unless disease related.
8. Free of prior malignancies for 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast.
9. A Urine Pregnancy Test (within 7 days of Day 1) is required for women with childbearing potential

Exclusion Criteria:

1. Pregnant or breast-feeding females.
2. Treatment including chemotherapy, chemo-immunotherapy , monoclonal antibody therapy, radiotherapy, high-dose corticosteroid therapy (more than 60 mg prednisone or equivalent daily), or immunotherapy within 21 days prior to enrollment or concurrent with this trial.
3. Investigational agent received within 30 days prior to the first dose of study drug or have previously taken PCI-32765. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 1 or less prior to first dose of study drug.
4. Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
5. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).
6. Patients with severe hematopoietic insufficiency, as defined by an absolute neutrophil count of less than 500/micro-L and/or a platelet count of less than 30,000/micro-L at time of screening for this protocol.
7. Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo therapy with PCI-32765 and rituximab.
8. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
9. Significant screening ECG abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, and QTc \> 470 msec.
10. Any serious medical condition, laboratory abnormality, or psychiatric illness that places the subject at unacceptable risk if he/she were to participate in the study.
11. History of stroke or cerebral hemorrhage within 6 months.
12. Evidence of bleeding diathesis or coagulopathy.
13. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study.
14. Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 1. Bone marrow aspiration and/or biopsy are allowed.
15. Serious, non-healing wound, ulcer, or bone fracture.
16. Treatment with Coumadin. Patients who recently received Coumadin must be off Coumadin for at least 7 days prior to start of the study.
17. Any chemotherapy (e.g., bendamustine, cyclophosphamide, pentostatin, or fludarabine), immunotherapy (e.g., alemtuzumab, or ofatumumab), bone marrow transplant, experimental therapy, or radiotherapy is prohibited during therapy on this study.
18. Use of medications known to prolong QTc interval or that may be associated with Torsades de Pointes (refer to Appendix F) are prohibited within 7 days of starting study drug and during study-drug treatment.
19. Requires treatment with strong CYP3A4/5 and/or CYP2D6 inhibitors.
C: Inclusion Criteria:

* Has responded to ofatumumab treatment (CR, nPR, PR) or has had SD at least up to and including visit number 14 (24 weeks after first infusion) in the Hx-CD20-406 trial.
* Has disease progression after visit number 14 (24 weeks after first infusion) in the Hx CD20 406 trial.
* Received at least eight ofatumumab infusions.
* Has active CLL with an indication for treatment.
* Has Eastern Cooperative Oncology Group (ECOG) performance status grade 0, 1 or 2.
* Provides signed informed consent, following receipt of verbal and written information about the trial, before any trial related activity is carried out.
* If previously treated in GEN416 (this trial), the patient must have achieved CR with subsequent disease progression 24 weeks or later after the first infusion in the GEN416 trial.

Exclusion Criteria:

* The disease has transformed to more aggressive B-cell malignancies (e.g. diffuse large B-cell lymphoma, Richter's syndrome or prolymphocytic leukemia).
* Has a suspected treatment requiring malignancy other than CLL.
* Has received treatment other than ofatumumab within two weeks prior to visit 2.
* Has clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from visit 1, congestive heart failure (NYHA III IV), and arrhythmia requiring therapy, with the exception of clinically non-significant extra systoles or minor conduction abnormalities.
* Has significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.
* Has a history of significant cerebrovascular disease.
* Is known HIV positive.
* Has positive serology for hepatitis B, defined as a positive test for HBsAg and/or positive tests for both anti-HBs and anti-HBc.
* Has known or suspected hypersensitivity to components of the IMP.
* Has received treatment with any non-marketed drug substance or experimental therapy other than ofatumumab within four weeks prior to visit 2.
* Currently participates in any other interventional clinical trial other than Hx-CD20-406.
* Known or suspected to not being able to comply with a trial protocol (e.g. due to alcoholism, drug dependency or psychiatric disorder).
* Is breast feeding (women only).
* Has a positive pregnancy test at screening (women only).
* Is not willing to use adequate contraception during the trial and one year after last dose of ofatumumab (women only). Adequate contraception is defined as hormonal birth control or intrauterine device. For patients in the US the use of double barrier method is considered adequate.
D: 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

Answer: C