Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma - CLL/SLL
Conditions
Interventions
Subjects randomly assigned to Arm A (I+VEN) will receive ibrutinib (420 mg/day
orally) given as leadin treatment for 3 cycles. Starting at Cycle 4, venetoclax
dose ramp up (from 20 mg to 400 mg over
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Adult subjects who are: , a. >=65 years old or, , b. 18 to 64 years old and have at least 1 of the following:, - Cumulative Illness Rating Scale (CIRS) score >6, - Creatinine clearance (CrCl) estimated <70 mL/min using the Cockcroft-Gault equation., 2. Diagnosis of CLL or SLL that meets iwCLL criteria. , 3. Active CLL/SLL requiring treatment per the iwCLL criteria: , a. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia or thrombocytopenia or both;, b. Massive (ie, at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly;, c. Massive nodes (ie, at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy;, d. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time of less than six months;, e. Constitutional symptoms, defined as 1 or more of the following:, - Unintentional weight loss >=10% within the previous 6 months prior to the start of screening;, - Significant fatigue (inability to work or perform usual activities);, - Fevers higher than 100.5°F or 38.0°C for 2 or more weeks without evidence of infection; , - Night sweats for more than 1 month without evidence of infection., 4. Measurable nodal disease (by computed tomography [CT]) is defined as at least one lymph node >;1.5 cm in longest diameter. , 5. ECOG Performance Status Grade =750 cells/µL independent of growth factor support;, b. Platelets >=50,000 cells/µL independent of transfusion support for at least 7 days prior to randomization;, c. Hemoglobin >8.0 g/dL independent of transfusion support for at least 7 days prior to randomization;, d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =30 mL/min (Cockcroft-Gault equation).
Exclusion criteria
Exclusion criteria: 1. Prior anti-leukemic therapy for CLL or SLL., 2. Presence of del17p or known TP53 mutation., 3. Major surgery within 4 weeks of first dose of study treatment. , 4. Known bleeding disorders (eg, von Willebrand*s disease or hemophilia)., 5. Central nervous system (CNS) involvement or suspected Richter*s syndrome., 6. An individual organ/system impairment score of 4 as assessed by CIRS, except for the eyes, ears, nose, throat, and larynx system, limiting the ability to receive treatment in this study., 7. Uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia (Coombs positivity in the absence of hemolysis is not an exclusion)., 8. Chronic use of corticosteroids more than 20 mg/day of prednisone or its equivalent within 7 days of initiation of study treatment., 9. History of prior malignancy, except:, a. Malignancy treated with curative intent and with no known active disease present for >=24 months before randomization;, b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;, c. Adequately treated cervical carcinoma in situ without evidence of disease;, d. Malignancy, which is considered cured with minimal risk of recurrence., 10. Received live, attenuated vaccine within 4 weeks of randomization., 11. History of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic condition that in the opinion of the investigator would adversely affect a subject*s participation in the study., 12. Currently active, clinically significant Child-Pugh Class B or C hepatic impairment according to the Child Pugh classification (see Attachment 4 Child-Pugh classification), 13. Uncontrolled active systemic infection or any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator*s opinion, could compromise the subject*s safety or put the study outcomes at undue risk., 14. Inability or difficulty swallowing capsules/tablets, malabsorption syndrome, or any disease or medical condition significantly affecting gastrointestinal function.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy evaluations will include imaging, physical examinations, evaluation of blood and bone marrow, disease-related symptoms, and assessment of patient-reported outcomes (PRO). Safety evaluations will include adverse event (AE) monitoring, physical examinations, laboratory tests, and review of concomitant medications. | — |
Secondary
| Measure | Time frame |
|---|---|
| To better understand the molecular and protein markers associated with response to and relapse following study treatment, bone marrow and peripheral blood samples will be collected. For subjects assigned to the I+VEN treatment arm, sparse samples will be collected for pharmacokinetic (PK) analysis. | — |
Countries
Netherlands
Outcome results
None listed