DNA Plasmid Encoding a Modified Human Telomerase Reverse Transcriptase (hTERT), Invac-1 in Chronic Lymphocytic Leukemia

Group 1: Untreated high risk "watch and wait" Inclusion Criteria: 1. Age ≥ 18 years old 2. Rai stage 0 - II without active disease according to IWCLL 2018 criteria 3. Predicted time to first treatment of ≤3 years according to MDACC nomogram. 4. ECOG performance status of 0-2 5. Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) \< 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 1.5 x ULN except Gilbert's Syndrome where a direct bilirubin ≤ 1.5 ULN will be used. 6. Adequate renal function, defined as an estimated creatinine clearance ≥30 mL/min using the Cockcroft-Gault equation 7. Willingness to receive all outpatient treatment, all laboratory monitoring, and all radiological evaluations at the institution that administers study drug for the entire study 8. Willingness of male and female patients, if sexually active, to use an effective barrier method of contraception during the study and for 3 months following the last dose of study drug 9. Ability to provide written informed consent and to understand and comply with the requirements of the study Exclusion Criteria 1. Any investigational agent(s) within 4 weeks prior to entry 2. Uncontrolled autoimmune hemolytic anemia (Hgb \< 11g/deciliter) or idiopathic thrombocytopenic purpura (\< 100,000/µl) 3. Any previous treatment (chemotherapy, radiotherapy, and/or monoclonal antibodies) intended specifically to treat CLL 4. Treatment with corticosteroids other than physiological replacement within the previous week or treatment with immunosuppressive medication within the previous week. 5. Major surgery within 4 weeks prior to inclusion 6. Currently active, clinically significant cardiovascular disease or a history of myocardial infarction within 6 months prior to inclusion 7. Uncontrolled active systemic fungal, bacterial, viral, or other infection or requirement for intravenous (IV) antibiotics 8. Known history of infection with human immunodeficiency virus (HIV) 9. Serologic status reflecting active hepatitis B or C infection. 10. History of stroke or intracranial hemorrhage within 6 months prior to enrolment 11. Current life-threatening illness, medical condition, or organ-system dysfunction that could compromise patient safety or put the study at risk 12. Breast-feeding or pregnant women, or patients for whom there is a risk of conception and who are unable or unwilling to use appropriate contraception (for male and female patients up to 4 months after end of ibrutinib.) 13. Previous malignancy with life expectancy less than 6 months or requiring systemic treatment (except colorectal cancer, history of basal cell carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment) 14. Known drug abuse/ alcohol abuse 15. Severe organ failures or diseases, including: clinically relevant coronary disease, myocardial infarction or any other relevant cardiovascular disorder within 12 months before study entry, severe psychiatric illness and severe infection. Group 2: Ibrutinib treated patients Inclusion Criteria 1. Age ≥ 18 years old 2. Males or females with CLL diagnosed according to IWCLL diagnostic criteria who have been treated with ibrutinib therapy for at least 12 months and have had no more than 1 other treatment for CLL prior to receiving ibrutinib. 3. Currently in complete or partial remission (PR)/PR with lymphocytosis (PRL) 4. MRD positivity defined as \>0.5% CLL cells in the bone marrow by flow cytometry 5. ECOG performance status of 0-2 6. Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) \< 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 1.5 x ULN, unless Gilbert's Syndrome where a direct bilirubin ≤ 1.5 ULN will be used. 7. Adequate renal function, defined as estimated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation 8. Willingness to receive all outpatient treatment, all laboratory monitoring, and all radiological evaluations at the institution that administers study drug for the entire study 9. Willingness of male and female patients, if sexually active, to use an effective barrier method of contraception during the study and for 3 months following the last dose of study drug 10. Ability to provide written informed consent and to understand and comply with the requirements of the study Exclusion Criteria 1. Any investigational agent(s) within 4 weeks prior to entry 2. Known involvement of the central nervous system by lymphoma or leukemia 3. History or current evidence of Richter's transformation or prolymphocytic leukemia 4. Uncontrolled autoimmune hemolytic anemia (Hgb \< 11g/deciliter) or idiopathic thrombocytopenic purpura (\< 100,000/µl) 5. More than one previous treatment by chemotherapy or patients who previously received alemtuzumab intended specifically to treat CLL 6. Corticosteroid use within 1 week prior to first dose of study drug, with the exception of inhaled, topical, or other local administrations. Patients requiring systemic steroids at daily doses \> 20 mg prednisone (or corticosteroid equivalent), or those who are administered steroids for leukemia control or white blood cell (WBC)-count-lowering are excluded 7. Major surgery within 4 weeks prior to inclusion 8. Currently active, clinically significant cardiovascular disease or a history of myocardial infarction within 6 months prior to inclusion 9. Uncontrolled active systemic fungal, bacterial, viral, or other infection or requirement for intravenous (IV) antibiotics 10. Known history of infection with human immunodeficiency virus (HIV) 11. Serologic status reflecting active hepatitis B or C infection 12. History of stroke or intracranial hemorrhage within 6 months prior to enrollment 13. Current life-threatening illness, medical condition, or organ-system dysfunction that could compromise patient safety or put the study at risk 14. Requirement for anticoagulation with warfarin, or for treatment with a strong CYP3A4/5 and/or CYP2D6 inhibitor 15. Breast-feeding or pregnant women, or patients for whom there is a risk of conception and who are unable or unwilling to use appropriate contraception (for male and female patients up to 4 months after end of ibrutinib.) 16. Previous malignancy with life expectancy less than 6 months or requiring systemic treatment (except colorectal cancer, history of basal cell or squamous carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment) 17. Known drug abuse/ alcohol abuse 18. Severe organ failures or diseases, including: clinically relevant coronary disease, myocardial infarction or any other relevant cardiovascular disorder within 12 months before study entry, severe psychiatric illness and severe infection.