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)

NCT06291220 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: M24-2912023-507637-19
• Study Type: interventional
• Target: 4
• Locations: 5 countries
• Sites: 21

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. Participants will be enrolled with a specific target dose and receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the appropriate target dose is achieved. Approximately 60 adult participants with previously R/R CLL/SLL will be enrolled in the study in approximately 40 sites across the world. Participants 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. The estimated study duration is 3 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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

Chronic Lymphocytic Leukemia: Small Lymphocytic Lymphoma; SLL; CLL; ABBV-453

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Adverse Events (AEs)

  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.

  Up to 3 Years

• Maximum Administered Dose (MAD) of ABBV-453

  MAD is defined as the highest administered dose if no maximum tolerated dose (MTD) is determined.

  Up to 18 Months

• Maximum Tolerated Dose (MTD) of ABBV-453

  MTD is defined as the highest dose administered that does not result in a final determination of de-escalate at that dose level.

  Up to 18 Months

Secondary Outcomes (10)

• Maximum Observed Plasma Concentration (Cmax) of ABBV-453

  Up to 30 Months

• Time to Maximum Observed Concentration (Tmax) of ABBV-453

  Up to 30 Months

• Area Under the Plasma/Serum Concentration Versus Time Curve (AUC) of ABBV-453

  Up to 30 Months

• Overall Response Rate (ORR)

  Up to 3 Years

• Duration of Response (DOR) for Participants with PR/nPR or Better

  Up to 3 Years

Study Arms (1)

Part A: Cohort 1.1 ABBV-453 Dose A

EXPERIMENTAL

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.

Drug: Obinutuzumab; Drug: ABBV-453

Interventions

Obinutuzumab DRUG

Intravenous Infusion

Part A: Cohort 1.1 ABBV-453 Dose A

ABBV-453 DRUG

Oral; Tablet

Part A: Cohort 1.1 ABBV-453 Dose A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (21)

City of Hope /ID# 253904

Duarte, California, 91010, United States

Location

City of Hope - Orange County Lennar Foundation Cancer Center /ID# 267158

Irvine, California, 92618, United States

Location

Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana /ID# 264622

Billings, Montana, 59102, United States

Location

Atrium Health /ID# 265136

Charlotte, North Carolina, 28204-2963, United States

Location

Duplicate_Duke Cancer Center /ID# 258707

Durham, North Carolina, 27710-3000, United States

Location

MD Anderson Cancer Center /ID# 253713

Houston, Texas, 77030, United States

Location

Royal Prince Alfred Hospital /ID# 263129

Sydney, New South Wales, 2050, Australia

Location

Gold coast University Hospital /ID# 255785

Southport, Queensland, 4215, Australia

Location

Austin Health /ID# 256776

Heidelberg, Victoria, 3084, Australia

Location

Royal Perth Hospital /ID# 256464

Perth, Western Australia, 6000, Australia

Location

Universitaetsklinikum Ulm /ID# 263148

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Universitaetsklinikum Halle (Saale) /ID# 263299

Halle, Saxony-Anhalt, 06120, Germany

Location

Universitaetsklinikum Schleswig-Holstein - Campus Kiel /ID# 263150

Kiel, Schleswig-Holstein, 24105, Germany

Location

Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin /ID# 263433

Berlin, 12203, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf /ID# 263730

Hamburg, 20246, Germany

Location

Yitzhak Shamir Medical Center /ID# 257626

Ẕerifin, Central District, 70300, Israel

Location

Hadassah Medical Center-Hebrew University /ID# 254721

Jerusalem, Jerusalem, 91120, Israel

Location

The Chaim Sheba Medical Center /ID# 254383

Ramat Gan, Tel Aviv, 5265601, Israel

Location

IRCCS Ospedale San Raffaele /ID# 263064

Milan, Milano, 20132, Italy

Location

IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 263065

Bologna, 40138, Italy

Location

Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia /ID# 263062

Perugia, 06156, Italy

Location

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

obinutuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: March 4, 2024
• Study Start: January 27, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); IL (3); DE (5); AU (4); US (6)