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)

AbbVie

Status and phase: Enrolling; Phase 1

Conditions: Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Treatments: Drug: Obinutuzumab; Drug: ABBV-453

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. 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 28 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.

Enrollment: 80 estimated 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 anti-cancer systemic therapies and does not have another therapy that is more appropriate at the judgement of the Investigator.
• 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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80 participants in 7 patient groups

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: ABBV-453

Drug: Obinutuzumab

Part A: Cohort 1.2 ABBV-453 Dose B

Experimental group

Description:

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.

Treatment:

Drug: ABBV-453

Drug: Obinutuzumab

Part A: Cohort 1.3 ABBV-453 Dose C

Experimental group

Description:

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.

Treatment:

Drug: ABBV-453

Drug: Obinutuzumab

Part A: Cohort 1.4 ABBV-453 Dose D

Experimental group

Description:

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.

Treatment:

Drug: ABBV-453

Drug: Obinutuzumab

Part A: Cohort 1.5 ABBV-453 Dose E

Experimental group

Description:

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.

Treatment:

Drug: ABBV-453

Drug: Obinutuzumab

Part B: Cohort 2.1 ABBV-453 Dose E

Experimental group

Description:

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.

Treatment:

Drug: ABBV-453

Drug: Obinutuzumab

Part B: Cohort 2.2 ABBV-453 Dose E

Experimental group

Description:

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.

Treatment:

Drug: ABBV-453