Lirilumab With Rituximab for Relapsed, Refractory or High-risk Untreated Chronic Lymphocytic Leukemia (CLL) Patients
Condition: Leukemia; Chronic Lymphocytic Leukemia; Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Lirilumab; Rituximab
Intervention description: 3 mg/kg by vein given on Day 1 of each 28 day cycle.; 375 mg/m2 by vein weekly for the first 4 weeks on Days 1,8, 15, and 22 of Cycle 1. After Cycle 1, given on Day 1 of Cycles 2 - 12.
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Chronic Lymphocytic Leukemia; CLL; Refractory/Relapsed; Untreated with high-risk molecular features; Small lymphocytic leukemia; SLL; Lirilumab; Rituximab; Rituxan

Summary:

      The goal of this clinical research study is to learn if lirilumab in combination with
      rituximab can help to control either CLL or Small lymphocytic lymphoma (SLL). The safety of
      the drug combination will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients will have a diagnosis of CLL or SLL who meet one or more criteria for active
             disease as defined by the International Working Group for CLL (IWCLL) and are: a.
             Cohort 1: refractory to and/or relapsed after at least one prior therapy OR b. Cohort
             2: untreated patients with high-risk molecular features such as del(17p), mutated
             TP53, del(11q), unmutated IGHV gene, or are >65 years of age

          2. Age 18 years or older

          3. Eastern Cooperative Oncology Group (ECOG) Performance Status </=2

          4. Patients must have adequate renal and hepatic function: Serum bilirubin </=1.5 x upper
             limit of normal (ULN). For patients with Gilbert's disease, serum bilirubin up to </=3
             x ULN is allowed provided normal direct bilirubin; Serum creatinine ≤1.5 x ULN;
             alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </=3 x ULN

          5. Females of childbearing potential must have a negative serum or urine beta human
             chorionic gonadotrophin (Beta-hCG) pregnancy test result within 24 hours prior to the
             first dose of treatment and must agree to use an effective contraception method during
             the study and for 12 months following the last dose of the study drugs. Females of
             non- childbearing potential are those who are postmenopausal greater than 1 year or
             who have had a bilateral tubal ligation or hysterectomy. Males who have partners of
             childbearing potential must agree to use an effective contraceptive method during the
             study and for 31 weeks following the last dose of study drugs.

          6. Patients or their legally authorized representative must provide written informed
             consent.

        Exclusion Criteria:

          1. Prior malignancy active within the previous 2 years except for locally curable cancers
             that have been apparently cured, such as basal or squamous cell skin cancer,
             superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized
             prostate cancer. If patients have another malignancy that was treated within the last
             2 years, such patients may be enrolled if the likelihood of requiring systemic therapy
             for this other malignancy within 2 years is less than 10%, as determined by an expert
             in that particular malignancy at MD Anderson Cancer Center and after consultation with
             the Principal Investigator.

          2. Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy,
             experimental therapy within 4 weeks prior to the first dose of the study drugs. For
             oral targeted therapies (such as ibrutinib, idelalisib, venetoclax), a washout of 3
             days is allowed. Note: Prior treatment with anti CD20 monoclonal antibody, anti CD52
             monoclonal antibody and lenalidomide are allowed. Prior treatment with anti-CTLA-4 and
             anti-PD1 therapies is allowed after a wash-out of 5 half-lives.

          3. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias,
             congestive heart failure, or myocardial infarction within 2 months of screening, or
             any Class 3 or 4 cardiac disease as defined by the New York Heart Association
             Functional Classification.

          4. History of stroke or cerebral hemorrhage within 2 months.

          5. Patients who have uncontrolled hypertension (defined as sustained systolic blood
             pressure >/= 160 mmHg or diastolic >/= 100 mmHg).

          6. Known evidence of active cerebral/meningeal CLL. Patients may have history of central
             nervous system (CNS) leukemic involvement if definitively treated with prior therapy
             and no evidence of active disease at the time of registration.

          7. Active, uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring
             steroid therapy.

          8. Patients with autoimmune diseases are excluded: Patients with a history of
             Inflammatory Bowel Disease (including Crohn's disease and ulcerative colitis) are
             excluded from this study as are patients with a history of autoimmune disease (e.g.,
             rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus,
             Wegener's granulomatosis).

          9. Patients with previous allogeneic stem cell transplant (SCT) within 6 months or with
             active acute or chronic graft-versus host disease are excluded. Patients must be off
             immunosuppression for graft versus host disease (GVHD) for at least 60 days before
             Cycle 1 Day 1.

         10. Patients with organ allografts (such as renal transplant) are excluded.

         11. History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis (NASH), auto
             immune, or grade 3-4 drug-related hepatitis).

         12. Patients who are on high-dose steroids (doses >10mg/day of prednisone or equivalent)
             or immune suppression medications. Note: Patients on high-dose steroids (doses
             >10mg/day of prednisone or equivalent) or immune suppression medications are eligible
             provided these drugs are discontinued at least 3 days prior to starting on the study
             drugs.

         13. Patients with uncontrolled active infection (viral, bacterial, and fungal) are not
             eligible.

         14. Current or chronic hepatitis B or C infection, or known seropositivity for HIV.

         15. Patient is pregnant or breast-feeding.

         16. Concurrent use of investigational therapeutic agent

         17. Patients may not receive other concurrent chemotherapy, radiotherapy, or
             immunotherapy. Localized radiotherapy to an area not compromising bone marrow function
             does not apply.

         18. Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that in the opinion of the investigator may increase the risk associated
             with study participation or investigational product administration or may interfere
             with the interpretation of study results and/or would make the patient inappropriate
             for enrollment into this study.