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) (453 Ph1 CLL)

AbbVie

Status and phase: Active, not recruiting; Phase 1

Conditions: Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Treatments: Drug: ABBV-453; Drug: Obinutuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06291220

M24-291

2023-507637-19 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 4 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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4 participants in 1 patient group

Part A: Cohort 1.1 ABBV-453 Dose A

Experimental group

Description:

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.

Treatment:

Drug: Obinutuzumab

Drug: ABBV-453