Study to Evaluate Adverse Events and Change in Disease Activity in Adult Participants With B-Cell Malignancies Receiving Oral ABBV-525 Tablets

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A First-in-Human Study of ABBV-525 (MALT1 Inhibitor) in B-Cell Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05618028
• Other study ID #: M23-324
• Status: Recruiting
• Phase: Phase 1
• Start date: April 4, 2023
• Est. completion date: June 27, 2027

Study information

• Verified date: April 2024
• Source: AbbVie
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

B-cell malignancies are a group of cancers of B lymphocytes, a type of white blood cell responsible for fighting infections. The purpose of this study is to assess safety, tolerability, pharmacokinetics and preliminary efficacy of ABBV-525 as a monotherapy.

ABBV-525 is an investigational drug being developed for the treatment of B-Cell Malignancies. Study doctors put the participants in groups called treatment arms. Participants will receive ABBV-525 at different doses. Approximately 100 adult participants will be enrolled in the study across sites worldwide.

In part 1 (dose escalation), participants will receive escalating oral doses of ABBV-525. In part 2 (dose optimization), participants will receive one of two oral doses of ABBV-525, until the recommended phase 2 dose (RP2D) is determined. In part 3 (dose expansion), participants will receive the RP2D oral dose of ABBV-525. The estimated duration of the study is up to 64 months.

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 and may require frequent medical assessments, blood tests, and scans.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 27, 2027
• Est. primary completion date: June 27, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Dose Escalation (Part 1) Only: Participants with a documented diagnosis of one of the following third line or later of treatment (3L)+ mature B-cell malignancies, from the World Health Organization (WHO)-defined histologies as defined in the protocol.

• Dose Optimization (Part 2) Only: Participants with documented diagnosis of chronic lymphocytic leukemia (CLL) who are 3L+, +/- cysteine-to-serine point mutation at residue 481 of BTK-domain active site (C481S with histology based on WHO criteria, with measurable disease requiring treatment as defined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL).

• Dose Expansion (Part 3) Only: Participants with documented diagnosis of non-germinal center B cell (GCB) Diffuse large B-cell lymphoma (DLBCL) who are 3L+ chimeric antigen receptor T-cells (CAR-T)/Hematopoietic cell transplant (HCT) relapsed/refractory (R/R) and/or ineligible with histology based on WHO criteria, with measurable disease requiring treatment.

• Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.

• Participant has a life expectancy >= 12 weeks.

• Adequate hematological and hepatic function as defined in the protocol.

• Must have archival or freshly collected tumor tissue for correlative studies before study enrollment.

• Participants with prior central nervous system (CNS) disease that has been effectively treated may be eligible.

• Participants with resolved coronavirus disease 2019 (COVID-19) infection are eligible.

Exclusion Criteria:

• Known active CNS disease, or primary CNS lymphoma.

• Known bleeding disorders.

• Known history of stroke or intracranial hemorrhage within 12 months prior to first dose of study treatment.

• Uncontrolled active systemic infection, or active cytomegalovirus infection.

• Active hepatitis B or C infection.

• Known history of human immunodeficiency virus (HIV).

• Known active COVID-19 infection. Participant must not have signs/symptoms associated with COVID-19 infection or known exposure to a confirmed case of COVID-19 infection during screening. If participant has signs/symptoms suggestive of COVID-19 infection, the participant must have a negative molecular (eg, polymerase chain reaction) test or 3 negative antigen test results at least 24 hours apart.

Related Conditions & MeSH terms

• B Cell Malignancies
• Chronic Lymphocytic Leukemia
• Diffuse Large B-Cell Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Neoplasms
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• ABBV-525
Oral; Tablet

Locations

Country	Name	City	State
Australia	Monash University /ID# 246366	Clayton	Victoria
Australia	Alfred Health /ID# 248592	Melbourne	Victoria
Belgium	UZ Gent /ID# 246462	Gent	Oost-Vlaanderen
Belgium	Universitair Ziekenhuis Leuven /ID# 246461	Leuven	Vlaams-Brabant
France	CHRU Lille - Hopital Claude Huriez /ID# 252054	Lille	Nord
France	IUCT Oncopole /ID# 259409	Toulouse Cedex 9
Israel	Shamir Medical Center (Assaf Harofeh) /ID# 257711	Be'er Yaakov	HaMerkaz
Israel	Rabin Medical Center /ID# 257665	Haifa	H_efa
Israel	Hadassah Medical Center-Hebrew University /ID# 251441	Jerusalem	Yerushalayim
Israel	The Chaim Sheba Medical Center /ID# 251442	Ramat Gan	Tel-Aviv
Spain	Hospital Clinic de Barcelona /ID# 246543	Barcelona
Spain	Hospital Universitario Ramon y Cajal /ID# 246540	Madrid
United Kingdom	The Christie Hospital /ID# 250325	Manchester
United States	Levine Cancer Institute /ID# 246363	Charlotte	North Carolina
United States	Fort Wayne Medical Oncology and Hematology, Inc /ID# 250113	Fort Wayne	Indiana
United States	START Midwest /ID# 252359	Grand Rapids	Michigan
United States	University of Texas MD Anderson Cancer Center /ID# 245463	Houston	Texas
United States	University of California Los Angeles /ID# 246357	Los Angeles	California
United States	Mount Sinai Medical Center-Miami Beach /ID# 248251	Miami Beach	Florida
United States	Tulane Cancer Center Clinic /ID# 249586	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center-Koch Center /ID# 245459	New York	New York
United States	Northwest Medical Specialties - Tacoma /ID# 260376	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Israel,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AE)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is defined as any untoward medical occurrence, whether associated with study drug or not, that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event requiring medical or surgical intervention to prevent serious outcome.	Up to Approximately 64 Months
Primary	Number of Participants With Dose-Limiting Toxicities (DLT)	A DLT is defined as any AE for which a clear alternative cause cannot be established (eg, attributed to the disease under study, another disease, or to a concomitant medication by the study investigators or medical monitor).	Up to Approximately 28 Days
Primary	Number of Tumor Lysis Syndrome (TLS)	TLS is confirmed by evaluation of electrolyte and fluid status and renal status including urine output.	Up to Approximately 64 Months
Primary	Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters	Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator will assess the results for clinical significance.	Up to Approximately 64 Months
Primary	Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters	Vital sign parameters included body temperature, systolic and diastolic blood pressure, pulse rate, and respiratory rate. The investigator will assess the results for clinical significance.	Up to Approximately 64 Months
Primary	Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)	A standard 12-lead ECG will be performed. The investigator will assess the results for clinical significance.	Up to Approximately 64 Months
Primary	Maximum Observed Plasma Concentration (Cmax) of ABBV-525	Maximum observed plasma concentration of ABBV-525.	Up to 12 Months
Primary	Time to Cmax (Tmax) of ABBV-525	Time to Cmax of ABBV-525.	Up to 12 Months
Primary	Area Under the Plasma Concentration-Time Curve (AUC) of ABBV-525	Area under the plasma concentration-time curve of ABBV-525.	Up to 12 Months
Secondary	Overall Response Rate (ORR)	ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR)/very good partial response (VGPR)/partial response (PR) in participants receiving at least 1 dose of study drug.	Up to Approximately 64 Months
Secondary	Duration of Response (DOR)	DOR is defined for participants achieving CR/VGPR/PR as the time from the initial response per Investigator review to disease progression or death of any cause, whichever occurs earlier.	Up to Approximately 64 Months