a study assessing adverse event and how oral abbv-453 moves through the body in adult participants with relapsed or refractory (r/r) chronic lymphocytic leukemia (cll)/small lymphocytic lymphoma (sll)

Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Summary: chronic lymphocytic leukemia (cll) is the most common leukemia in western countries. the purpose of this study is to assess how well abbv-453 works adult participants with relapsed/refractory (r/r) untreated cll/small lymphocytic lymphoma (sll). adverse events, pharmacokinetics, and change in disease activity will be assessed. abbv-453 is an investigational drug for the treatment of cll and sll. there are 2 parts to this study. in part a participants will be placed 1 of 5 cohorts with a specific target dose for each cohort and receive obinutuzumab during the debulking period followed escalating doses of abbv-453, until the appropriate target dose is achieved. in part b participants will be placed in 2 cohorts and receive up to the maximum dose in part a, with cohort 2.1 including a debulking period (obinutuzumab) as in part a. approximately 80 adult participants with previously r/r cll/sll will be enrolled in the study in approximately 40 sites across the world. participants in part a will placed into 1 of 5 cohorts with a specific target dose for each cohort and will receive intravenous (iv) obinutuzumab as part of the debulking period, followed by escalating doses of oral abbv-453 until the appropriate target dose is achieved. participants in part b will be place in one of 2 cohorts. participants in cohort 2.1 will receive iv obinutuzumab as part of the debulking period, followed by escalating doses of oral abbv-453 until the maximum target dose from part a is achieved. participants in cohort 2.2 will receive no treatment during the the debulking period, followed by escalating doses of oral abbv-453 until the maximum target dose from part a is achieved. the estimated study duration is 5 years. there may be higher treatment burden for participants in this trial compared to their standard of care. participants will attend regular visits during the study at a hospital or clinic. the effect of the treatment will be checked by medical assessments, blood tests, and checking for side effects.


Eligibility criteria:
inclusion criteria: * relapsed/refractory (r/r) chronic lymphocytic leukemia (cll)/ small lymphocytic lymphoma (sll) that has received at least 2 prior systemic therapies and have no available (or established) therapies known to provide clinical benefit and to which the participant would consent to receiving. * laboratory values meeting those listed in the protocol. exclusion criteria: * qt interval corrected for heart rate (qtc) using fridericia's correction of \> 470 msec (females) or \> 450 msec (males), grade 3 arrythmia, and/or other clinically significant cardiac abnormalities. * known to be b-cell leukemia/lymphoma 2 inhibitor (bcl-2i) refractory or has received a bcl-2i-containing regimen within (6 months) of starting study drug (e.g., venetoclax, lisaftoclax, bgv-11417). * has active human immunodeficiency virus (hiv) infection. hiv testing is not required unless required locally. * recent history (within 6 months) of: * congestive heart failure (defined as new york heart association, class 2 or higher). * ischemic cardiovascular event. * cardiac arrhythmia requiring pharmacological or surgical intervention. * pericardial effusion. * pericarditis. * consumes known moderate or strong inhibitors of cytochrome p450 3a isoform subfamily (cyp3a) within 14 day or 5 half-lives of the drug (whichever is shorter) before the first dose of abbv-453.

Keywords: chronic lymphocytic leukemia: small lymphocytic lymphoma sll cll abbv-453