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)

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: ABBV-453; Drug: Obinutuzumab

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Cohort 1.1 ABBV-453 Dose A; 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: ABBV-453; Oral; Tablet; Drug: Obinutuzumab; Intravenous Infusion
Experimental: Part A: Cohort 1.2 ABBV-453 Dose B; 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.	Drug: ABBV-453; Oral; Tablet; Drug: Obinutuzumab; Intravenous Infusion
Experimental: Part A: Cohort 1.3 ABBV-453 Dose C; 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.	Drug: ABBV-453; Oral; Tablet; Drug: Obinutuzumab; Intravenous Infusion
Experimental: Part A: Cohort 1.4 ABBV-453 Dose D; 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.	Drug: ABBV-453; Oral; Tablet; Drug: Obinutuzumab; Intravenous Infusion
Experimental: Part A: Cohort 1.5 ABBV-453 Dose E; 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.	Drug: ABBV-453; Oral; Tablet; Drug: Obinutuzumab; Intravenous Infusion
Experimental: Part B: Cohort 2.1 ABBV-453 Dose E; 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.	Drug: ABBV-453; Oral; Tablet; Drug: Obinutuzumab; Intravenous Infusion
Experimental: Part B: Cohort 2.2 ABBV-453 Dose E; 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.	Drug: ABBV-453; Oral; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A and B: 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 5 Years
Part A: 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
Part A: 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A and B: Maximum Observed Plasma Concentration (Cmax) of ABBV-453	Cmax is defined as the maximum observed plasma/serum concentration of ABBV-453.	Up to 30 Months
Part A and B: Time to Maximum Observed Concentration (Tmax) of ABBV-453	Tmax is defined as the time to maximum observed concentration of ABBV-453.	Up to 30 Months
Part A and B: Area Under the Plasma/Serum Concentration Versus Time Curve (AUC) of ABBV-453	Area under the plasma/serum concentration versus time curve (AUC) of ABBV-453.	Up to 30 Months
Part A and B: Overall Response Rate (ORR)	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).	Up to 5 Years
Part A and B: Duration of Response (DOR) for Participants with PR/nPR or Better	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.	Up to 5 Years
Part A and B: Complete response rate (CRR)	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.	Up to 5 Years
Part A and B: Duration of Complete Response (DOCR)	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.	Up to 5 Years
Part A and B: Percentage of Participants Achieving an Minimal Residual Disease (MRD) Response among Participants Achieving a PR, nPR, CR, or CRi	MRD response is defined as < 1 cell in 10,000 leukocytes (< 10^-4).	Up to 5 Years
Part A and B: Progression-free survival (PFS)	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.	Up to 5 Years
Part A and B: Overall survival (OS)	OS is defined as the time from the first date of study treatment until date of death due to any cause.	Up to 5 Years

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): June 2, 2024
• Primary Completion (Estimated): July 21, 2029
• Study Completion (Estimated): July 21, 2029

Study Registration Dates

• First Submitted: February 27, 2024
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Estimated): March 4, 2024

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: CLL; SLL; ABBV-453; Chronic Lymphocytic Leukemia: Small Lymphocytic Lymphoma
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia, B-Cell; Chronic Disease; Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Antineoplastic Agents, Immunological; Obinutuzumab
• Other Study ID Numbers: M24-291; 2023-507637-19 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No