Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies

Hematologic Cancer Clinical Trial

Official title:

First-in-Human Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of the BTK Degrader, ABBV-101, in Participants With B-cell Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05753501
• Other study ID #: M23-647
• Secondary ID: 2023-503594-38-0
• Status: Recruiting
• Phase: Phase 1
• Start date: June 9, 2023
• Est. completion date: June 7, 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

Non-Hodgkin's lymphoma (NHL) is a cancer that arises from the transformation of normal B and T lymphocytes (white blood cells). The purpose of this study is to assess the safety, pharmacokinetics, and preliminary efficacy of ABBV-101 in adult participants in relapsed or refractory (R/R) non-Hodgkin's lymphomas: third line or later of treatment (3L) + chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large b-cell lymphoma (DLBCL), non-germinal center B cell (GCB) DLBCL, mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), or transformed indolent NHL. Adverse events will be assessed. ABBV-101 is an investigational drug being developed for the treatment of NHL. This study will include a dose escalation phase to determine the maximum administered dose (MAD)/Maximum tolerated dose (MTD) of ABBV-101 and a dose expansion phase to determine the change in disease activity in participants with CLL or non-GCB DLBCL. Approximately 128 adult participants with multiple NHL subtypes will be enrolled in the study in sites world wide. In the Dose Escalation phase of the study participants will receive escalating oral doses of ABBV-101, until the MAD/MTD is determined, as part of the approximately 60 month study duration. In the dose expansion phase of the study participants receive oral ABBV-101, as part of the approximately 60 month study duration . 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 an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 128
• Est. completion date: June 7, 2027
• Est. primary completion date: June 7, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• For Dose Escalation (Part 1) only: Participants with documented diagnosis for one of the following 3L+ B-cell malignancies, from one of the following WHO-defined

histologies (Swerdlow et al 2016):

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Chimeric antigen receptor T-cells (CAR-T)/hematopoietic cell transplant (HCT) relapsed/refractory (R/R) or ineligible diffuse large b-cell lymphoma (DLBCL) from the following histologies: DLBCL not otherwise specified (NOS) (germinal center B cell [GCB] and non-GCB DLBCL), T-cell/histiocyte-rich large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, anaplastic lymphoma kinase positive (ALK+) large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma NOS.
• Mantle cell lymphoma (MCL)
• Follicular lymphoma [FL] (grades 1-3b)
• Marginal zone lymphoma [MZL] (splenic, extranodal, and nodal)
• Waldenström macroglobulinemia (WM)
• Transformed indolent non-Hodgkin's lymphoma (iNHL)
• For Dose Expansion (Part 2) only: Participants with documented diagnosis of CLL who are 3L+ including those with Bruton's tyrosine kinase (BTK) mutations or CAR-T/HCT R/R or ineligible non-GCB DLBCL who are 3L+ with histology based on criteria established by the World Health Organization (WHO).
• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2.
• Participant has a life expectancy >= 12 weeks.
• Prior Bruton's tyrosine kinase inhibitor (BTKi) is allowed.
• Adequate hematologic, renal, and hepatic function per the protocol.
• Participants with prior central nervous system (CNS) disease that have been effectively treated may be eligible.

Exclusion Criteria:

• Previously treated with a Bruton's tyrosine kinase (BTK) degrader.
• Known active CNS disease, or primary CNS lymphoma.
• Uncontrolled active systemic infection, or active cytomegalovirus infection, known history of human immunodeficiency virus (HIV), active hepatitis B or C infection.

Related Conditions & MeSH terms

• Hematologic Cancer
• Hematologic Neoplasms

Intervention

Drug:
• ABBV-101
Oral:Tablet

Locations

Country	Name	City	State
Israel	Hadassah Medical Center-Hebrew University /ID# 251123	Jerusalem	Yerushalayim
Israel	The Chaim Sheba Medical Center /ID# 251122	Ramat Gan	Tel-Aviv
Israel	Tel Aviv Sourasky Medical Center /ID# 259608	Tel Aviv	Tel-Aviv
Israel	Assaf Harofeh Medical Center /ID# 254566	Zerifin	HaMerkaz
Japan	National Cancer Center Hospital /ID# 250680	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East /ID# 250684	Kashiwa-shi	Chiba
Japan	The Cancer Institute Hospital Of JFCR /ID# 260375	Koto-ku	Tokyo
Japan	Kyoto University Hospital /ID# 261837	Kyoto-shi	Kyoto
United States	New York Oncology Hematology - Albany Cancer Center /ID# 252240	Albany	New York
United States	Oncology Assoc. of Oregon PC - WVCI and Research Ctr - Springfield /ID# 249309	Eugene	Oregon
United States	MD Anderson Cancer Center /ID# 249293	Houston	Texas
United States	Northwell Health - Monter Cancer Center /ID# 250422	Lake Success	New York
United States	Rocky Mountain Cancer Centers /ID# 252237	Lone Tree	Colorado
United States	Rutgers Cancer Institute of New Jersey /ID# 249323	New Brunswick	New Jersey
United States	University of Pennsylvania /ID# 250341	Philadelphia	Pennsylvania
United States	University of Rochester Medical Center /ID# 249324	Rochester	New York
United States	Arizona Oncology Associates, PC-HOPE /ID# 252351	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Israel,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events (AE)	AE is defined as 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.	Up to Approximately Two Years
Primary	Change in Laboratory Parameters	Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.	Up to Approximately Two Years
Primary	Change in Vital Signs	Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.	Up to Approximately Two Years
Primary	Change in Electrocardiogram (ECG)	12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.	Up to Approximately Two Years
Secondary	Maximum Observed Serum Concentration (Cmax) of ABBV-101	Maximum observed serum concentration of ABBV-101.	Up to Approximately One Year
Secondary	Time to Cmax (Tmax) of ABBV-101	Time to Cmax of ABBV-101.	Up to Approximately One Year
Secondary	Area Under the Serum Concentration Versus Time Curve (AUC) of ABBV-101	Area under the serum concentration versus time curve (AUC) of ABBV-101.	Up to Approximately One Year
Secondary	Number of Participants with Response of Partial Response (PR) or Better per Disease-Specific Criteria	Number of participants with response of PR or better per disease-specific criteria.	Up to Approximately Two Years
Secondary	Duration of Response (DOR)	DOR is defined for participants achieving PR or better as the time from the initial response per Investigator review to disease progression or death of any cause, whichever occurs earlier.	Up to Approximately Two Years

External Links

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