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
Study Details
Study Description
Brief 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 in 28-day cycles, until the MAD/MTD is determined. In the dose expansion phase of the study participants receive oral ABBV-101 in 28-day cycles.
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Escalation ABBV-101 Participants with relapsed or refractory (R/R) Non-Hodgkin's lymphoma (NHL) will receive escalating doses of ABBV-101 in 28-day cycles, until the maximum administered dose (MAD)/Maximum tolerated dose (MTD) is determined. |
Drug: ABBV-101
Oral:Tablet
|
| Experimental: Dose Expansion ABBV-101 R/R Chronic Lymphocytic Lymphoma (CLL) Participants with R/R CLL will receive ABBV-101 at the dose determined in the dose escalation arm in 28-day cycles. |
Drug: ABBV-101
Oral:Tablet
|
| Experimental: Dose Expansion ABBV-101 R/R non-GCB DLBCL Participants with R/R non-germinal center B cell (GCB) diffuse large B-cell lymphoma (DLBCL) will receive ABBV-101 at the dose determined in the dose escalation arm in 28-day cycles. |
Drug: ABBV-101
Oral:Tablet
|
Outcome Measures
Primary Outcome Measures
- Number of Participants with Adverse Events (AE) [Up to Approximately Two Years]
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.
- Change in Laboratory Parameters [Up to Approximately Two Years]
Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.
- Change in Vital Signs [Up to Approximately Two Years]
Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.
- Change in Electrocardiogram (ECG) [Up to Approximately Two Years]
12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.
Secondary Outcome Measures
- Maximum Observed Serum Concentration (Cmax) of ABBV-101 [Up to Approximately One Year]
Maximum observed serum concentration of ABBV-101.
- Time to Cmax (Tmax) of ABBV-101 [Up to Approximately One Year]
Time to Cmax of ABBV-101.
- Area Under the Serum Concentration Versus Time Curve (AUC) of ABBV-101 [Up to Approximately One Year]
Area under the serum concentration versus time curve (AUC) of ABBV-101.
- Number of Participants with Response of Partial Response (PR) or Better per Disease-Specific Criteria [Up to Approximately Two Years]
Number of participants with response of PR or better per disease-specific criteria.
- Duration of Response (DOR) [Up to Approximately Two Years]
DOR is defined for participants achieving a complete response (CR)/PR as the time from the initial response per investigator review to disease progression or death of any cause, whichever occurs earlier.
Eligibility Criteria
Criteria
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)
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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).
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Has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or
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Participant has a life expectancy >= 12 weeks.
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Prior Bruton's tyrosine kinase inhibitor (BTKi) is allowed.
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Adequate hematologic, renal, and hepatic function per the protocol.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rocky Mountain Cancer Centers /ID# 252237 | Lone Tree | Colorado | United States | 80124 |
| 2 | New York Oncology Hematology - Albany Cancer Center /ID# 252240 | Albany | New York | United States | 12206-5013 |
| 3 | Northwell Health - Monter Cancer Center /ID# 250422 | Lake Success | New York | United States | 11042 |
| 4 | University of Rochester Cancer Center /ID# 249324 | Rochester | New York | United States | 14642-0001 |
| 5 | University of Pennsylvania /ID# 250341 | Philadelphia | Pennsylvania | United States | 19104 |
| 6 | MD Anderson Cancer Center /ID# 249293 | Houston | Texas | United States | 77030 |
| 7 | The Chaim Sheba Medical Center /ID# 251122 | Ramat Gan | Tel-Aviv | Israel | 5265601 |
| 8 | Hadassah Medical Center-Hebrew University /ID# 251123 | Jerusalem | Yerushalayim | Israel | 91120 |
Sponsors and Collaborators
- AbbVie
Investigators
- Study Director: ABBVIE INC., AbbVie
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- M23-647
- 2023-503594-38-00