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
- Registration Number
- NCT05753501
- Lead Sponsor
- AbbVie
- 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 244 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 88 month study duration. In the dose expansion phase of the study participants receive oral ABBV-101, as part of the approximately 88 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 244
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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 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.
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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.
- 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 or less than 12 weeks since achieving undetectable viral load in cases of prior active hepatitis C.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation ABBV-101 ABBV-101 Participants with relapsed or refractory (R/R) Non-Hodgkin's lymphoma (NHL) will receive escalating doses of ABBV-101, until the maximum administered dose (MAD)/Maximum tolerated dose (MTD) is determined, as part of the approximately 88 month study duration. Dose Expansion ABBV-101 R/R Chronic Lymphocytic Lymphoma (CLL) ABBV-101 Participants with R/R CLL will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 88 month study duration. Dose Expansion ABBV-101 R/R non-GCB DLBCL ABBV-101 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, as part of the approximately 88 month study duration.
- Primary Outcome Measures
Name Time Method Number of Participants with Adverse Events (AE) Up to Approximately 88 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 Outcome Measures
Name Time Method 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 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.
Trial Locations
- Locations (44)
A.O.U. CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO - Ospedale Molinette /ID# 253530
🇮🇹Torino, Piemonte, Italy
Arizona Oncology Associates, PC-HOPE /ID# 252351
🇺🇸Tempe, Arizona, United States
University College London Hospital /ID# 260202
🇬🇧London, Greater London, United Kingdom
UC Irvine Medical Center /ID# 263020
🇺🇸Orange, California, United States
Stanford Cancer Center - Palo Alto /ID# 249683
🇺🇸Palo Alto, California, United States
Rocky Mountain Cancer Centers - Lone Tree /ID# 252237
🇺🇸Lone Tree, Colorado, United States
Northwestern University Feinberg School of Medicine /ID# 249347
🇺🇸Chicago, Illinois, United States
Beth Israel Deaconess Medical Center /ID# 249302
🇺🇸Boston, Massachusetts, United States
Rutgers Cancer Institute of New Jersey /ID# 249323
🇺🇸New Brunswick, New Jersey, United States
New York Oncology Hematology - Albany Cancer Center /ID# 252240
🇺🇸Albany, New York, United States
Northwell Health - Monter Cancer Center /ID# 250422
🇺🇸Lake Success, New York, United States
University of Rochester Medical Center /ID# 249324
🇺🇸Rochester, New York, United States
UC Health - Cincinnati /ID# 249299
🇺🇸Cincinnati, Ohio, United States
MD Anderson Cancer Center /ID# 249293
🇺🇸Houston, Texas, United States
CHUM Notre-Dame Hospital /ID# 253428
🇨🇦Montreal, Quebec, Canada
Oncology Assoc. of Oregon PC - WVCI and Research Ctr - Springfield /ID# 249309
🇺🇸Eugene, Oregon, United States
Institut Bergonie /ID# 253664
🇫🇷Bordeaux, Gironde, France
University of Pennsylvania /ID# 250341
🇺🇸Philadelphia, Pennsylvania, United States
CHU Montpellier - Hopital Saint Eloi /ID# 253666
🇫🇷Montpellier Cedex 5, Herault, France
CHU de Nantes, Hotel Dieu -HME /ID# 256248
🇫🇷Nantes, Pays-de-la-Loire, France
Institut Gustave Roussy /ID# 253662
🇫🇷Villejuif Cedex, Val-de-Marne, France
Hôpital Saint-Louis /ID# 253663
🇫🇷Paris, France
Universitaetsklinikum Ulm /ID# 253742
🇩🇪Ulm, Baden-Wuerttemberg, Germany
Universitaetsklinikum Wuerzburg /ID# 254636
🇩🇪Wuerzburg, Bayern, Germany
Universitaetsmedizin Rostock /ID# 259657
🇩🇪Rostock, Mecklenburg-Vorpommern, Germany
CHRU Lille - Hopital Claude Huriez /ID# 253665
🇫🇷Lille, Nord, France
Universitaetsklinikum des Saarlandes /ID# 257435
🇩🇪Homburg, Saarland, Germany
Charite Universitaetsklinikum Berlin - Campus Benjamin Franklin /ID# 257431
🇩🇪Berlin, Germany
Yitzhak Shamir Medical Center /ID# 254566
🇮🇱Zerifin, HaMerkaz, 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
Hadassah Medical Center-Hebrew University /ID# 251123
🇮🇱Jerusalem, Yerushalayim, Israel
IRCCS Ospedale San Raffaele /ID# 253531
🇮🇹Milan, Milano, Italy
National Cancer Center Hospital East /ID# 250684
🇯🇵Kashiwa-shi, Chiba, Japan
Kyoto University Hospital /ID# 261837
🇯🇵Kyoto-shi, Kyoto, Japan
National Cancer Center Hospital /ID# 250680
🇯🇵Chuo-ku, Tokyo, Japan
The Cancer Institute Hospital Of JFCR /ID# 260375
🇯🇵Koto-ku, Tokyo, Japan
Hospital Universitario Puerta de Hierro - Majadahonda /ID# 260196
🇪🇸Majadahonda, Madrid, Spain
Hospital Universitario Vall d'Hebron /ID# 260447
🇪🇸Barcelona, Spain
Hospital Universitario Ramon y Cajal /ID# 260450
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca /ID# 253656
🇪🇸Salamanca, Spain
Addenbrooke's Hospital /ID# 256242
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Leicester Royal Infirmary /ID# 255171
🇬🇧Leicester, England, United Kingdom
King's College Hospital NHS Foundation Trust /ID# 253670
🇬🇧London, United Kingdom