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

NCT05753501 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: M23-6472023-503594-38-00
• Study Type: interventional
• Target: 135
• Locations: 9 countries
• Sites: 51

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 and a dose expansion phase to determine the change in disease activity in participants with first line treatment (1L), second line or later of treatment (2L)+ CLL/SLL or third line or later of treatment (3L) non-GCB DLBCL. Approximately 340 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.

Conditions

Hematologic Cancer

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

Outcome Measures

Primary Outcomes (4)

• 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 88 Months

• 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

• 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

• 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 Outcomes (5)

• Maximum Observed Serum Concentration (Cmax) of ABBV-101

  Up to Approximately One Year

• Time to Cmax (Tmax) of ABBV-101

  Up to Approximately One Year

• Area Under the Serum Concentration Versus Time Curve (AUC) of ABBV-101

  Up to Approximately One Year

• Number of Participants with Response of Partial Response (PR) or Better Response (Overall Response) per Disease-Specific Criteria

  Up to Approximately Two Years

• Duration of Response (DOR)

  Up to Approximately Two Years

Study Arms (3)

Dose Escalation ABBV-101

EXPERIMENTAL

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.

Drug: ABBV-101

Dose Expansion ABBV-101 R/R CLL/SLL

EXPERIMENTAL

Participants with R/R chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL) will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 88 month study duration.

Drug: ABBV-101

Dose Expansion ABBV-101 R/R non-GCB DLBCL

EXPERIMENTAL

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.

Drug: ABBV-101

Interventions

ABBV-101 DRUG

Oral:Tablet

Dose Escalation ABBV-101; Dose Expansion ABBV-101 R/R CLL/SLL; Dose Expansion ABBV-101 R/R non-GCB DLBCL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For Dose Escalation (Part 1) 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 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)
• 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 Escalation (Part 1) - BTKi/BTKd-naïve CLL/SLL backfill only: 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.
• For Dose Escalation (Part 1) - BTKi/BTKd-naïve CLL/SLL backfill only: 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.
• For Dose Expansion (Part 2) CLL/SLL only: Participants with a documented diagnosis of CLL/SLL who have received at least one prior systemic therapy.
• For Dose Expansion (Part 2) 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 a documented diagnosis of CAR-T/HCT R/R or ineligible non-GCB DLBCL in their third line or later treatment 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. For EU only: Participant has an ECOG PS of 0 or 1.
• Participant has a life expectancy \>= 12 weeks.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (51)

Arizona Oncology Associates, PC-HOPE /ID# 252351

Tempe, Arizona, 85284-1812, United States

Location

UC Irvine Medical Center /ID# 263020

Orange, California, 92868-3201, United States

Location

Stanford University /ID# 249683

Palo Alto, California, 94304, United States

Location

Rocky Mountain Cancer Centers - Lone Tree /ID# 252237

Lone Tree, Colorado, 80124, United States

Location

Northwestern University Feinberg School of Medicine /ID# 249347

Chicago, Illinois, 60611-2927, United States

Location

Beth Israel Deaconess Medical Center /ID# 249302

Boston, Massachusetts, 02215-5400, United States

Location

Rutgers Cancer Institute of New Jersey /ID# 249323

New Brunswick, New Jersey, 08901, United States

Location

New York Oncology Hematology - Albany Cancer Center /ID# 252240

Albany, New York, 12206-5013, United States

Location

Northwell Health - Monter Cancer Center /ID# 250422

Lake Success, New York, 11042, United States

Location

University of Rochester Medical Center /ID# 249324

Rochester, New York, 14642-0001, United States

Location

UC Health - Cincinnati /ID# 249299

Cincinnati, Ohio, 45267-2800, United States

Location

Oncology Assoc. of Oregon PC - WVCI and Research Ctr - Springfield /ID# 249309

Eugene, Oregon, 97401-6036, United States

Location

University of Pennsylvania /ID# 250341

Philadelphia, Pennsylvania, 19104, United States

Location

MD Anderson Cancer Center /ID# 249293

Houston, Texas, 77030, United States

Location

University Health Network_Princess Margaret Cancer Centre /ID# 253483

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM Notre-Dame Hospital /ID# 253428

Montreal, Quebec, H2L 4M1, Canada

Location

Institut Bergonie /ID# 253664

Bordeaux, Gironde, 33000, France

Location

CHU Montpellier - Hopital Saint Eloi /ID# 253666

Montpellier, Herault, 34295, France

Location

CHRU Lille - Hopital Claude Huriez /ID# 253665

Lille, Nord, 59037, France

Location

Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 256248

Nantes, Pays de la Loire Region, 44000, France

Location

Institut Gustave Roussy /ID# 253662

Villejuif, Val-de-Marne, 94805, France

Location

Hopital Saint-Louis /ID# 253663

Paris, 75010, France

Location

Universitaetsklinikum Ulm /ID# 253742

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Universitaetsklinikum Wuerzburg /ID# 254636

Würzburg, Bavaria, 97080, Germany

Location

Universitaetsmedizin Rostock /ID# 259657

Rostock, Mecklenburg-Vorpommern, 18057, Germany

Location

Universitaetsklinikum des Saarlandes /ID# 257435

Homburg, Saarland, 66424, Germany

Location

Charite Universitaetsklinikum Berlin - Campus Benjamin Franklin /ID# 257431

Berlin, 12203, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf /ID# 264566

Hamburg, 20246, Germany

Location

Yitzhak Shamir Medical Center /ID# 254566

Ẕerifin, Central District, 70300, Israel

Location

Hadassah Medical Center-Hebrew University /ID# 251123

Jerusalem, Jerusalem, 91120, Israel

Location

The Chaim Sheba Medical Center /ID# 251122

Ramat Gan, Tel Aviv, 5265601, Israel

Location

Tel Aviv Sourasky Medical Center /ID# 259608

Tel Aviv, Tel Aviv, 6423906, Israel

Location

IRCCS Ospedale San Raffaele /ID# 253531

Milan, Milano, 20132, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda /ID# 253532

Milan, Milano, 20162, Italy

Location

A.O.U. CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO - Ospedale Molinette /ID# 253530

Turin, Piedmont, 10126, Italy

Location

ASST Papa Giovanni XXIII /ID# 260317

Bergamo, 24127, Italy

Location

IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 255172

Bologna, 40138, Italy

Location

National Cancer Center Hospital East /ID# 250684

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Kyoto University Hospital /ID# 261837

Kyoto, Kyoto, 606-8507, Japan

Location

National Cancer Center Hospital /ID# 250680

Chuo-ku, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital Of JFCR /ID# 260375

Koto-ku, Tokyo, 135-8550, Japan

Location

Hospital Universitario Puerta de Hierro - Majadahonda /ID# 260196

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Vall de Hebron /ID# 260447

Barcelona, 08035, Spain

Location

Hospital Universitario Ramon y Cajal /ID# 260450

Madrid, 28034, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz /ID# 253654

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro /ID# 253655

Madrid, 28050, Spain

Location

Hospital Universitario de Salamanca /ID# 253656

Salamanca, 37711, Spain

Location

Addenbrookes Hospital /ID# 256242

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

Location

Leicester Royal Infirmary /ID# 255171

Leicester, England, LE1 5WW, United Kingdom

Location

University College London Hospital /ID# 260202

London, Greater London, NW1 2BU, United Kingdom

Location

Kings College Hospital NHS Foundation Trust /ID# 253670

London, Greater London, SE5 9RS, United Kingdom

Location

Related Links

• Related info

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2023
• First Posted: March 3, 2023
• Study Start: June 9, 2023
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): March 1, 2031
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (6); IL (4); CA (2); FR (6); JP (4); ES (6); GB (4); US (14); IT (5)