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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06291220




Registration number
NCT06291220
Ethics application status
Date submitted
27/02/2024
Date registered
4/03/2024
Date last updated
5/11/2024

Titles & IDs
Public title
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)
Scientific 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)
Secondary ID [1] 0 0
2023-507637-19
Secondary ID [2] 0 0
M24-291
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - ABBV-453

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.

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.

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.

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.

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.

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.

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.


Treatment: Drugs: Obinutuzumab
Intravenous Infusion

Treatment: Drugs: ABBV-453
Oral; Tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A and B: Percentage of Participants With Adverse Events (AEs)
Timepoint [1] 0 0
Up to 5 Years
Primary outcome [2] 0 0
Part A: Maximum Administered Dose (MAD) of ABBV-453
Timepoint [2] 0 0
Up to 18 Months
Primary outcome [3] 0 0
Part A: Maximum Tolerated Dose (MTD) of ABBV-453
Timepoint [3] 0 0
Up to 18 Months
Secondary outcome [1] 0 0
Part A and B: Maximum Observed Plasma Concentration (Cmax) of ABBV-453
Timepoint [1] 0 0
Up to 30 Months
Secondary outcome [2] 0 0
Part A and B: Time to Maximum Observed Concentration (Tmax) of ABBV-453
Timepoint [2] 0 0
Up to 30 Months
Secondary outcome [3] 0 0
Part A and B: Area Under the Plasma/Serum Concentration Versus Time Curve (AUC) of ABBV-453
Timepoint [3] 0 0
Up to 30 Months
Secondary outcome [4] 0 0
Part A and B: Overall Response Rate (ORR)
Timepoint [4] 0 0
Up to 5 Years
Secondary outcome [5] 0 0
Part A and B: Duration of Response (DOR) for Participants with PR/nPR or Better
Timepoint [5] 0 0
Up to 5 Years
Secondary outcome [6] 0 0
Part A and B: Complete response rate (CRR)
Timepoint [6] 0 0
Up to 5 Years
Secondary outcome [7] 0 0
Part A and B: Duration of Complete Response (DOCR)
Timepoint [7] 0 0
Up to 5 Years
Secondary outcome [8] 0 0
Part A and B: Percentage of Participants Achieving an Minimal Residual Disease (MRD) Response among Participants Achieving a PR, nPR, CR, or CRi
Timepoint [8] 0 0
Up to 5 Years
Secondary outcome [9] 0 0
Part A and B: Progression-free survival (PFS)
Timepoint [9] 0 0
Up to 5 Years
Secondary outcome [10] 0 0
Part A and B: Overall survival (OS)
Timepoint [10] 0 0
Up to 5 Years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
21/07/2029
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital /ID# 263129 - Sydney
Recruitment hospital [2] 0 0
Austin Health /ID# 256776 - Heidelberg
Recruitment postcode(s) [1] 0 0
2050 - Sydney
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Montana
Country [3] 0 0
Germany
State/province [3] 0 0
Hamburg
Country [4] 0 0
Israel
State/province [4] 0 0
HaMerkaz
Country [5] 0 0
Israel
State/province [5] 0 0
Tel-Aviv
Country [6] 0 0
Israel
State/province [6] 0 0
Yerushalayim

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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. 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.
Trial website
https://clinicaltrials.gov/study/NCT06291220
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
844-663-3742
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06291220