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NCT Number: 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)

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Royal Prince Alfred Hospital /ID# 263129, Sydney, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Obinutuzumab

Drug

Intravenous Infusion

ABBV-453

Drug

Oral; Tablet

Primary outcomes

  1. Percentage of Participants With Adverse Events (AEs)

    Time frame: Up to 3 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.

  2. Maximum Administered Dose (MAD) of ABBV-453

    Time frame: Up to 18 Months

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

  3. Maximum Tolerated Dose (MTD) of ABBV-453

    Time frame: 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 outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of ABBV-453

    Time frame: Up to 30 Months

    Cmax is defined as the maximum observed plasma/serum concentration of ABBV-453.

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

    Time frame: Up to 30 Months

    Tmax is defined as the time to maximum observed concentration of ABBV-453.

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

    Time frame: Up to 30 Months

    Area under the plasma/serum concentration versus time curve (AUC) of ABBV-453.

  4. Overall Response Rate (ORR)

    Time frame: Up to 3 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).

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

    Time frame: Up to 3 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.

  6. Complete response rate (CRR)

    Time frame: Up to 3 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.

  7. Duration of Complete Response (DOCR)

    Time frame: Up to 3 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.

  8. Percentage of Participants Achieving an Minimal Residual Disease (MRD) Negativity Among Participants Achieving a PR, nPR, CR, or CRi

    Time frame: Up to 3 Years

    MRD response is defined as < 1 cell in 10,000 leukocytes (< 10^-4).

  9. Progression-free survival (PFS)

    Time frame: Up to 3 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.

  10. Overall survival (OS)

    Time frame: Up to 3 Years

    OS is defined as the time from the first date of study treatment until date of death due to any cause.

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Registry information

Official study 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)

Acronym: 453 Ph1 CLL

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Mar 4, 2024
Registry last updated
Jan 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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