A Randomized, Open-label, Phase 3 study of the Combination of Ibrutinib plus Venetoclax versus Chlorambucil plus Obinutuzumab for the First-line Treatment of Subjects with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
- Conditions
- Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma - CLL/SLL10024324
- Registration Number
- NL-OMON54563
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 23
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 <=2., 6. Adequate organ function defined as
follows:, a. Absolute neutrophil count (ANC) >=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) <=3.0 x upper limit of normal (ULN);, e. Total bilirubin
<=1.5 x ULN (unless due to Gilbert*s syndrome);, f. Estimated CrCl >=30 mL/min
(Cockcroft-Gault equation).
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Efficacy evaluations will include imaging, physical examinations, evaluation of<br /><br>blood and bone marrow, disease-related symptoms, and assessment of<br /><br>patient-reported outcomes (PRO). Safety evaluations will include adverse event<br /><br>(AE) monitoring, physical examinations, laboratory tests, and review of<br /><br>concomitant medications.</p><br>
- Secondary Outcome Measures
Name Time Method <p>To better understand the molecular and protein markers associated with response<br /><br>to and relapse following study treatment, bone marrow and peripheral blood<br /><br>samples will be collected. For subjects assigned to the I+VEN treatment arm,<br /><br>sparse samples will be collected for pharmacokinetic (PK) analysis.</p><br>