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 LeukemiaSmall Lymphocytic Lymphoma
- Interventions
- Registration Number
- NCT06291220
- Lead Sponsor
- AbbVie
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
- 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.
-
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.
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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).
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Has active human immunodeficiency virus (HIV) infection. HIV testing is not required unless required locally.
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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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Cohort 1.1 ABBV-453 Dose A ABBV-453 Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose A is achieved, during the 5 year study duration. Part A: Cohort 1.2 ABBV-453 Dose B Obinutuzumab Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose B is achieved, during the 5 year study duration. Part A: Cohort 1.2 ABBV-453 Dose B ABBV-453 Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose B is achieved, during the 5 year study duration. Part A: Cohort 1.3 ABBV-453 Dose C ABBV-453 Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose C is achieved, during the 5 year study duration. Part A: Cohort 1.4 ABBV-453 Dose D Obinutuzumab Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose D is achieved, during the 5 year study duration. Part A: Cohort 1.4 ABBV-453 Dose D ABBV-453 Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose D is achieved, during the 5 year study duration. Part A: Cohort 1.5 ABBV-453 Dose E Obinutuzumab Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose E is achieved, during the 5 year study duration. Part B: Cohort 2.1 ABBV-453 Dose E Obinutuzumab Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose E is achieved, during the 5 year study duration. Part A: Cohort 1.5 ABBV-453 Dose E ABBV-453 Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose E is achieved, during the 5 year study duration. Part B: Cohort 2.1 ABBV-453 Dose E ABBV-453 Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose E is achieved, during the 5 year study duration. Part B: Cohort 2.2 ABBV-453 Dose E ABBV-453 Participants will no participate in the debulking period and receive escalating doses of ABBV-453, until the dose E is achieved, during the 5 year study duration. Part A: Cohort 1.1 ABBV-453 Dose A Obinutuzumab Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose A is achieved, during the 5 year study duration. Part A: Cohort 1.3 ABBV-453 Dose C Obinutuzumab Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose C is achieved, during the 5 year study duration.
- Primary Outcome Measures
Name Time Method Part A and B: Percentage of Participants With Adverse Events (AEs) Up to 5 Years An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
Part A: Maximum Administered Dose (MAD) of ABBV-453 Up to 18 Months MAD is defined as the highest administered dose if no maximum tolerated dose (MTD) is determined.
Part A: Maximum Tolerated Dose (MTD) of ABBV-453 Up to 18 Months MTD is defined as the highest dose administered that does not result in a final determination of de-escalate at that dose level.
- Secondary Outcome Measures
Name Time Method Part A and B: Maximum Observed Plasma Concentration (Cmax) of ABBV-453 Up to 30 Months Cmax is defined as the maximum observed plasma/serum concentration of ABBV-453.
Part A and B: Overall Response Rate (ORR) Up to 5 Years Percentage of participants achieving a complete response (CR), complete response with incomplete count recovery (CRi), partial response (PR), or nodular partial response (nPR) using disease-specific criteria per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL, 2018).
Part A and B: Duration of Response (DOR) for Participants with PR/nPR or Better Up to 5 Years DOR is defined as the time between the initial PR or better response assessment per Investigator according to iwCLL criteria to the time of progressive disease (PD) or death of any cause, whichever occurs earlier.
Part A and B: Time to Maximum Observed Concentration (Tmax) of ABBV-453 Up to 30 Months Tmax is defined as the time to maximum observed concentration of ABBV-453.
Part A and B: Area Under the Plasma/Serum Concentration Versus Time Curve (AUC) of ABBV-453 Up to 30 Months Area under the plasma/serum concentration versus time curve (AUC) of ABBV-453.
Part A and B: Complete response rate (CRR) Up to 5 Years CRR is defined as the percentage of participants with a best overall response (BOR) of CR or CRi per Investigator review according to iwCLL for participants with relapsed or refractory CLL/SLL, regardless of reasons for study drug discontinuation, and prior to start of subsequent anti-cancer therapies in the participants receiving at least one dose of ABBV-453 monotherapy.
Part A and B: Duration of Complete Response (DOCR) Up to 5 Years DOCR is defined as the time between the initial CR/CRi response assessment per Investigator according to iwCLL criteria to the time of PD or death of any cause, whichever occurs earlier.
Part A and B: Percentage of Participants Achieving an Minimal Residual Disease (MRD) Negativity Among Participants Achieving a PR, nPR, CR, or CRi Up to 5 Years MRD response is defined as \< 1 cell in 10,000 leukocytes (\< 10\^-4).
Part A and B: Progression-free survival (PFS) Up to 5 Years PFS is defined as time from first study treatment to a documented PD (based on iwCLL criteria) as determined by the Investigator, or death due to any cause, whichever occurs earlier.
Part A and B: Overall survival (OS) Up to 5 Years OS is defined as the time from the first date of study treatment until date of death due to any cause.
Trial Locations
- Locations (21)
Universitaetsklinikum Ulm /ID# 263148
🇩🇪Ulm, Baden-Wuerttemberg, Germany
City of Hope /ID# 253904
🇺🇸Duarte, California, United States
City of Hope Orange County Lennar Foundation Cancer Center /ID# 267158
🇺🇸Irvine, California, United States
Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana /ID# 264622
🇺🇸Billings, Montana, United States
Atrium Health /ID# 265136
🇺🇸Charlotte, North Carolina, United States
Duke Cancer Center /ID# 258707
🇺🇸Durham, North Carolina, United States
MD Anderson Cancer Center /ID# 253713
🇺🇸Houston, Texas, United States
Royal Prince Alfred Hospital /ID# 263129
🇦🇺Sydney, New South Wales, Australia
Gold coast University Hospital /ID# 255785
🇦🇺SouthPort, Queensland, Australia
Austin Health /ID# 256776
🇦🇺Heidelberg, Victoria, Australia
Royal Perth Hospital /ID# 256464
🇦🇺Perth, Western Australia, Australia
Universitaetsklinikum Schleswig-Holstein - Campus Kiel /ID# 263150
🇩🇪Kiel, Schleswig-Holstein, Germany
Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin /ID# 263433
🇩🇪Berlin, Germany
Universitaetsklinikum Halle (Saale) /ID# 263299
🇩🇪Halle (Saale), Germany
Universitaetsklinikum Hamburg-Eppendorf /ID# 263730
🇩🇪Hamburg, Germany
Yitzhak Shamir Medical Center /ID# 257626
🇮🇱Zerifin, HaMerkaz, Israel
The Chaim Sheba Medical Center /ID# 254383
🇮🇱Ramat Gan, Tel-Aviv, Israel
Hadassah Medical Center-Hebrew University /ID# 254721
🇮🇱Jerusalem, Yerushalayim, Israel
IRCCS Ospedale San Raffaele /ID# 263064
🇮🇹Milan, Milano, Italy
IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 263065
🇮🇹Bologna, Italy
Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia /ID# 263062
🇮🇹Perugia, Italy