Clinical trial NCT02420938 (phase 2, status: withdrawn)
Conditions: leukemia
ICD codes: C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01
Drugs: rituximab, urelumab
SMILES: ClCCN(CCCl)P1(=O)NCCCO1
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 relapsed
             and/or refractory after at least one prior therapy.

          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, -- ALT and 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. Acceptable methods of
             contraception are condoms with contraceptive foam; oral, implantable or injectable
             contraceptives; contraceptive patch; intrauterine device; diaphragm with spermicidal
             gel; or a sexual partner who is surgically sterilized or post-menopausal.

          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,
             (third-degree AV block, ventricular tachycardia, atrial fibrillation with rapid
             ventricular rate (HR >100 bpm)),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 CNS
             leukemic involvement if definitively treated with prior therapy and no evidence of
             active disease at the time of registration.

          7. Known 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 GVHD for at least 30 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. Note:
             Patients with previous history of Hepatitis B (who have cleared the infection and have
             natural immunity, i.e. Hep B core antibody positive cases) are excluded if prophylaxis
             against Hep B reactivation with antiviral agents (such as entecavir) is recommended,
             after consultation with gastroenterologist/hepatologist or infectious disease team.

         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.

         19. Patients with Richter's transformation are not allowed in the study.