Hematologic Cancer
Conditions
Keywords
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), Mantle cell lymphoma (MCL), Follicular lymphoma (FL), Marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), Transformed Indolent non-Hodgkin's lymphoma (INHL), Hematologic Cancer, ABBV-101
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: 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. Dose expansion part 2A will follow to further determine the safety and change in disease activity in participants with first line treatment (1L\[non-US only\]), second line or later of treatment (2L)+ CLL/SLL or third line or later of treatment (3L+) non-GCB DLBCL receiving ABBV-101 alone. Dose expansion Part 2B (non-US only) will follow to determine the safety and change in disease activity in participants with 1L or 2L+ CLL/SLL receiving ABBV-101 in combination with oral venetoclax. Approximately 390 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 100 month study duration. In the dose expansion phase of the study participants receive oral ABBV-101 alone or oral ABBV-101 at a dose determined in the dose escalation phase in combination with oral venetoclax, as part of the approximately 100 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.
Interventions
DRUGABBV-101
Oral:Tablet
DRUGVenetoclax
Oral
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For Dose Escalation (Part 1) only (including backfill): Participants have received at least two prior systemic therapies, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), have measurable disease requiring treatment, and have a documented diagnosis for one of the following third line or later B-cell malignancies, from one of the following world health organization (WHO)-defined histologies (Swerdlow et al 2016): * Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) 1. For Dose Escalation (Part 1) backfill only - Bruton's tyrosine kinase inhibitor (BTKi)/Bruton's tyrosine kinase degrader (BTKd)-naïve CLL/SLL. Participants with a documented diagnosis of CLL/SLL who have received at least one prior systemic therapy that cannot be a BTK inhibitor or degrader, and, with the exception of BTK pathway agents, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), and have measurable disease requiring treatment. 2. For Dose Escalation (Part 1) backfill only - BTKi/BCL-2i combination regimen-exposed 2L CLL/SLL. Participants with a documented diagnosis of CLL/SLL who have received one prior systemic therapy with a BTKi and BCL-2i combination regimen, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), and have measurable disease requiring treatment. * 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 2a) CLL/SLL only: Participants with a documented diagnosis of CLL/SLL in their first-line or later treatment. * For Dose Expansion (Part 2a) DLBCL only: Participants have received at least two prior systemic therapies, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), have measurable disease requiring treatment, and have documented diagnosis of CAR-T/HCT R/R or ineligible non-GCB DLBCL who are in their third line or later treatment with histology based on criteria established by the WHO. * For Dose Exploration of ABBV-101 combination with venetoclax (Part 2b) CLL/SLL only: Participants with a documented diagnosis of CLL/SLL in their first-line or later treatment: In safety lead-in for each dose level, participants must have received at least one prior systemic therapy. * Has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2. For EU only: Participant has an ECOG PS of 0 or 1. * 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.
Exclusion criteria
* Previously treated with a Bruton's tyrosine kinase (BTK) degrader. * Known active central nervous system (CNS) disease, or primary CNS lymphoma. Participants with prior CNS disease that have been effectively treated may be eligible. * Uncontrolled active systemic infection requiring systemic treatment that is ongoing or was completed \<= 14 days before the first dose of study drug, or active cytomegalovirus infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events (AE) | Up to Approximately 100 Months | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Maximum Observed Serum Concentration (Cmax) of Venetoclax | Up to Approximately One Year | Maximum observed serum concentration of venetoclax. |
| Time to Cmax (Tmax) of Venetoclax | Up to Approximately One Year | Time to Cmax of venetoclax. |
| Area Under the Serum Concentration Versus Time Curve (AUC) of Venetoclax | Up to Approximately One Year | Area under the serum concentration versus time curve (AUC) of venetoclax. |
| Number of Participants with Response of Partial Response (PR) or Better Response (Overall Response) per Disease-Specific Criteria | Up to Approximately Two Years | Number of participants with response of PR or better response (overall response) per disease-specific criteria. |
| Duration of Response (DOR) | Up to Approximately Two Years | 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. |
Countries
Canada, France, Germany, Israel, Italy, Japan, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed