Back to resultsStudy to Evaluate Adverse Events and Change in Disease Activity in Adult Participants With B-Cell Malignancies Receiving Oral ABBV-525 Tablets
Primary Purpose
Diffuse Large B-Cell Lymphoma, Chronic Lymphocytic Leukemia, B Cell Malignancies
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ABBV-525
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring Diffuse Large B-Cell Lymphoma, B-cell Malignancies, Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma, ABBV-525, Cancer
Eligibility Criteria
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.
Sites / Locations
- Mount Sinai Medical Center-Miami Beach /ID# 248251
- Norton Healthcare /ID# 246362
- Tulane Cancer Center Clinic /ID# 249586Recruiting
- Cancer & Hematology Centers /ID# 252359Recruiting
- Memorial Sloan Kettering Cancer Center-Koch Center /ID# 245459Recruiting
- Levine Cancer Ins, Carolina Me /ID# 246363
- University of Texas MD Anderson Cancer Center /ID# 245463Recruiting
- Paratus Clinical Research Woden /ID# 247859
- Alfred Health /ID# 248592
- Monash University /ID# 246366
- UZ Gent /ID# 246462
- Universitair Ziekenhuis Leuven /ID# 246461
- CHRU Lille - Hopital Claude Huriez /ID# 252054
- CHU Toulouse /ID# 252193
- Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 252062
- University of Cologne /ID# 246646
- The Chaim Sheba Medical Center /ID# 251442
- Hadassah Medical Center-Hebrew University /ID# 251441
- Hospital Universitario Vall d'Hebron /ID# 245475
- Hospital Clinic de Barcelona /ID# 246543
- Institut Catala d'Oncologia -Hospital Duran i Reynals /ID# 246537
- Hospital Universitario Ramon y Cajal /ID# 246540
- Hospital Universitario 12 de Octubre /ID# 246538
- Leeds Teaching Hospitals NHS Trust /ID# 245470
- The Royal Marsden NHS Foundation Trust /ID# 250324
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
ABBV-525 Dose Escalation
ABBV-525 Dose Optimization
ABBV-525 Dose Expansion
Arm Description
Participants will receive escalating doses of ABBV-525 until doses for optimization are determined, as part of an approximately 64 month study period.
Participants will receive one of two doses of ABBV-525 until the recommended phase 2 dose (RP2D) is determined, as part of an approximately 64 month study period.
Participants will receive the RP2D dose of ABBV-525, as part of an approximately 64 month study period.
Outcomes
Primary Outcome Measures
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.
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).
Number of Tumor Lysis Syndrome (TLS)
TLS is confirmed by evaluation of electrolyte and fluid status and renal status including urine output.
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.
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.
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.
Maximum Observed Plasma Concentration (Cmax) of ABBV-525
Maximum observed plasma concentration of ABBV-525.
Time to Cmax (Tmax) of ABBV-525
Time to Cmax of ABBV-525.
Area Under the Plasma Concentration-Time Curve (AUC) of ABBV-525
Area under the plasma concentration-time curve of ABBV-525.
Secondary Outcome Measures
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05618028
Brief Title
Study to Evaluate Adverse Events and Change in Disease Activity in Adult Participants With B-Cell Malignancies Receiving Oral ABBV-525 Tablets
Official Title
A First-in-Human Study of ABBV-525 (MALT1 Inhibitor) in B-Cell Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 4, 2023 (Actual)
Primary Completion Date
July 2, 2027 (Anticipated)
Study Completion Date
July 2, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma, Chronic Lymphocytic Leukemia, B Cell Malignancies, Non-Hodgkin's Lymphoma
Keywords
Diffuse Large B-Cell Lymphoma, B-cell Malignancies, Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma, ABBV-525, Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ABBV-525 Dose Escalation
Arm Type
Experimental
Arm Description
Participants will receive escalating doses of ABBV-525 until doses for optimization are determined, as part of an approximately 64 month study period.
Arm Title
ABBV-525 Dose Optimization
Arm Type
Experimental
Arm Description
Participants will receive one of two doses of ABBV-525 until the recommended phase 2 dose (RP2D) is determined, as part of an approximately 64 month study period.
Arm Title
ABBV-525 Dose Expansion
Arm Type
Experimental
Arm Description
Participants will receive the RP2D dose of ABBV-525, as part of an approximately 64 month study period.
Intervention Type
Drug
Intervention Name(s)
ABBV-525
Intervention Description
Oral; Tablet
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AE)
Description
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.
Time Frame
Up to Approximately 64 Months
Title
Number of Participants With Dose-Limiting Toxicities (DLT)
Description
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).
Time Frame
Up to Approximately 28 Days
Title
Number of Tumor Lysis Syndrome (TLS)
Description
TLS is confirmed by evaluation of electrolyte and fluid status and renal status including urine output.
Time Frame
Up to Approximately 64 Months
Title
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters
Description
Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator will assess the results for clinical significance.
Time Frame
Up to Approximately 64 Months
Title
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters
Description
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.
Time Frame
Up to Approximately 64 Months
Title
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)
Description
A standard 12-lead ECG will be performed. The investigator will assess the results for clinical significance.
Time Frame
Up to Approximately 64 Months
Title
Maximum Observed Plasma Concentration (Cmax) of ABBV-525
Description
Maximum observed plasma concentration of ABBV-525.
Time Frame
Up to 12 Months
Title
Time to Cmax (Tmax) of ABBV-525
Description
Time to Cmax of ABBV-525.
Time Frame
Up to 12 Months
Title
Area Under the Plasma Concentration-Time Curve (AUC) of ABBV-525
Description
Area under the plasma concentration-time curve of ABBV-525.
Time Frame
Up to 12 Months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
Up to Approximately 64 Months
Title
Duration of Response (DOR)
Description
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.
Time Frame
Up to Approximately 64 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
ABBVIE CALL CENTER
Phone
844-663-3742
Email
abbvieclinicaltrials@abbvie.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ABBVIE INC.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Mount Sinai Medical Center-Miami Beach /ID# 248251
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140-2948
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Norton Healthcare /ID# 246362
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207-4700
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Tulane Cancer Center Clinic /ID# 249586
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Individual Site Status
Recruiting
Facility Name
Cancer & Hematology Centers /ID# 252359
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 245459
City
New York
State/Province
New York
ZIP/Postal Code
10065-6007
Country
United States
Individual Site Status
Recruiting
Facility Name
Levine Cancer Ins, Carolina Me /ID# 246363
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Texas MD Anderson Cancer Center /ID# 245463
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Paratus Clinical Research Woden /ID# 247859
City
Phillip
State/Province
Australian Capital Territory
ZIP/Postal Code
2606
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Alfred Health /ID# 248592
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Monash University /ID# 246366
City
Clayton
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
UZ Gent /ID# 246462
City
Gent
State/Province
Oost-Vlaanderen
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Not yet recruiting
Facility Name
Universitair Ziekenhuis Leuven /ID# 246461
City
Leuven
State/Province
Vlaams-Brabant
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Not yet recruiting
Facility Name
CHRU Lille - Hopital Claude Huriez /ID# 252054
City
Lille
State/Province
Hauts-de-France
ZIP/Postal Code
59037
Country
France
Individual Site Status
Not yet recruiting
Facility Name
CHU Toulouse /ID# 252193
City
Toulouse
State/Province
Occitanie
ZIP/Postal Code
31300
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 252062
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
University of Cologne /ID# 246646
City
Cologne
ZIP/Postal Code
50923
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
The Chaim Sheba Medical Center /ID# 251442
City
Ramat Gan
State/Province
Tel-Aviv
ZIP/Postal Code
5265601
Country
Israel
Individual Site Status
Not yet recruiting
Facility Name
Hadassah Medical Center-Hebrew University /ID# 251441
City
Jerusalem
State/Province
Yerushalayim
ZIP/Postal Code
91120
Country
Israel
Individual Site Status
Not yet recruiting
Facility Name
Hospital Universitario Vall d'Hebron /ID# 245475
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Hospital Clinic de Barcelona /ID# 246543
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Institut Catala d'Oncologia -Hospital Duran i Reynals /ID# 246537
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Hospital Universitario Ramon y Cajal /ID# 246540
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Hospital Universitario 12 de Octubre /ID# 246538
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Leeds Teaching Hospitals NHS Trust /ID# 245470
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
The Royal Marsden NHS Foundation Trust /ID# 250324
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Individual Site Status
Not yet recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.abbvieclinicaltrials.com/study/?id=M243-324
Description
Related Info.
Learn more about this trial
Study to Evaluate Adverse Events and Change in Disease Activity in Adult Participants With B-Cell Malignancies Receiving Oral ABBV-525 Tablets
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