Clinical trial NCT06291220: 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)
Official title: A Phase 1 Study Evaluating Safety, Pharmacokinetics, and Efficacy of ABBV-453 in Adult Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Keywords: Chronic Lymphocytic Leukemia: Small Lymphocytic Lymphoma
SLL
CLL
ABBV-453
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2024-03-04
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Part A and B: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to 5 Years
measure: Part A: Maximum Administered Dose (MAD) of ABBV-453
timeFrame: Up to 18 Months
measure: Part A: Maximum Tolerated Dose (MTD) of ABBV-453
timeFrame: Up to 18 Months
Secondary outcomes:
measure: Part A and B: Maximum Observed Plasma Concentration (Cmax) of ABBV-453
timeFrame: Up to 30 Months
measure: Part A and B: Time to Maximum Observed Concentration (Tmax) of ABBV-453
timeFrame: Up to 30 Months
measure: Part A and B: Area Under the Plasma/Serum Concentration Versus Time Curve (AUC) of ABBV-453
timeFrame: Up to 30 Months
measure: Part A and B: Overall Response Rate (ORR)
timeFrame: Up to 5 Years
measure: Part A and B: Duration of Response (DOR) for Participants with PR/nPR or Better
timeFrame: Up to 5 Years
measure: Part A and B: Complete response rate (CRR)
timeFrame: Up to 5 Years
measure: Part A and B: Duration of Complete Response (DOCR)
timeFrame: Up to 5 Years
measure: Part A and B: Percentage of Participants Achieving an Minimal Residual Disease (MRD) Negativity Among Participants Achieving a PR, nPR, CR, or CRi
timeFrame: Up to 5 Years
measure: Part A and B: Progression-free survival (PFS)
timeFrame: Up to 5 Years
measure: Part A and B: Overall survival (OS)
timeFrame: Up to 5 Years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope /ID# 253904
state: California
city: Irvine
country: United States
facility: City of Hope Orange County Lennar Foundation Cancer Center /ID# 267158
state: California
city: Billings
country: United States
facility: Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana /ID# 264622
state: Montana
city: Charlotte
country: United States
facility: Atrium Health /ID# 265136
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Center /ID# 258707
state: North Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center /ID# 253713
state: Texas
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital /ID# 263129
state: New South Wales
city: SouthPort
country: Australia
facility: Gold coast University Hospital /ID# 255785
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health /ID# 256776
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital /ID# 256464
state: Western Australia
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm /ID# 263148
state: Baden-Wuerttemberg
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein - Campus Kiel /ID# 263150
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin /ID# 263433
city: Halle (Saale)
country: Germany
facility: Universitaetsklinikum Halle (Saale) /ID# 263299
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf /ID# 263730
city: Zerifin
country: Israel
facility: Yitzhak Shamir Medical Center /ID# 257626
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 254383
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 254721
state: Yerushalayim
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele /ID# 263064
state: Milano
city: Bologna
country: Italy
facility: IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 263065
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia /ID# 263062
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: