Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Heart and Blood Diseases

Rare Diseases

Leukemia

Lymphoma, Large B-Cell, Diffuse

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

Waldenstrom Macroglobulinemia

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

Marginal Zone Lymphoma

Participants with Relapsed/Refractory (R/R) B-cell malignancies will receive escalating doses of ABBV-623.

Participants with R/R B-cell malignancies will receive escalating doses of ABBV-992.

Participants with R/R B-cell malignancies will receive escalating doses of ABBV-623 and ABBV-992.

Participants with R/R B-cell malignancies will receive ABBV-623 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.

Participants with R/R B-cell malignancies will receive ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.

Participants with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) will receive ABBV-623 and ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.

ABBV-623

ABBV-992

ABBVIE INC.

B-cell cancer is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). The main objective of this study is to evaluate the safety and efficacy of ABBV-623 and ABBV-992 given alone and in combination in treating B-cell cancers. Adverse events, change in disease activity and how the drug moves through the body of adult participants with B-cell cancers will be evaluated.

ABBV-623 and ABBV-992 are investigational drugs being developed for the treatment of B-cell cancer. Study doctors assign participants to one of six groups, called treatment arms. Approximately 105 adult participants with a diagnosis of B-cell cancer will be enrolled in the study at approximately 50 sites worldwide.

Participants in the combination expansion treatment arms will receive oral tablets of ABBV-623 and/or ABBV-992 once daily for 24 months. All other arms are treated until progression.

Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be evaluated by medical assessments and blood tests. Adverse events will be collected and assessed throughout the clinical trial.

Study to Evaluate Adverse Events, Change in Disease Activity, Movement of Oral ABBV-623 and ABBV-992 Tablets in the Body of Adult Participants With B-cell Cancers

A Phase 1 First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of ABBV-623 and ABBV-992 in Subjects With B-cell Malignancies

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.

The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that ABBV-623 achieves in the blood after administration in a dosing interval.

The area under the plasma concentration-time curve (AUC; measured in h\*ng/mL/mg) is a method of measurement of the total exposure of ABBV-623 in blood plasma.

The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that ABBV-992 achieves in the blood after administration in a dosing interval.

The area under the plasma concentration-time curve (AUC; measured in h\*ng/mL/mg) is a method of measurement of the total exposure of ABBV-992 in blood plasma.

ORR is the proportion of R/R CLL/SLL participants achieving a response of PR or better per IWCLL without the use of new anti-cancer therapy.

Partial response (PR) as per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) , Lugano, International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria in protocol.

Duration of Response (DOR) is defined as the time from the date of the participant's documented first response of PR or better to the date of documented disease progression or death due to the disease, whichever occurs first.

Time to response, defined as the length of time from the date of first dose of study drug to the date of first response of PR or better per disease-specific response criteria.

Undetectable minimal residual disease (uMRD) is described as less than one myeloma cell per million bone marrow cells.

Peripheral blood Undetectable minimal residual disease (uMRD) is described as less than one CLL cell per 10,000 leukocytes (or below 10\^-4) or as specified in the protocol.

Duration of response is defined as the time from the initial objective response to disease progression or death, whichever occurs first.

Time to response is defined by the time between the date of the first drug intake and the date of the first assessment having documented the response.

Progression free survival (PFS) is defined as the duration from start of the treatment to disease progression or death (regardless of cause of death), whichever comes first.

Overall Survival is defined as the number of days from the date the participant was randomized to the date of death.

AbbVie

Behaviors and Mental Disorders

Hematologic Neoplasms

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Quality of Life

Patients with CLL receiving systemic treatment (physician's choice)

Patients with DLBCL receiving systemic treatment (physician's choice)

Patients with FL receiving systemic treatment (physician's choice)

Patients with MCL receiving systemic treatment (physician's choice)

Patients with MZL receiving systemic treatment (physician's choice)

Patients with WM receiving systemic treatment (physician's choice)

Physician's choice according to patient's needs.

Routine care as per site standard.

Martina Jänicke, Dr.

Rainer Claus, Prof. Dr.

Tobias Dechow

Paul Graf La Rosée, Prof. Dr.

Jens Kisro, Dr.

Patrick Marschner, Dr.

Ingo Tamm, PD Dr.

Robert Zeiser, Prof. Dr.

The purpose of the project is to set up a national, prospective, longitudinal, multicenter registry platform to document uniform data on characteristics, molecular diagnostics, treatment and course of disease, to collect patient-reported outcomes and to establish a decentralized biobank for patients with hematological malignancies in Germany.

RUBIN is a national, observational, prospective, longitudinal, multicenter registry platform with the purpose to record information on the antineoplastic treatment of hematological malignancies in Germany.

It will identify common therapeutic sequences and changes in the treatment of the disease, and will analyse the impact of novel treatments on the outcome of patients in routine care. Unmet needs and areas with the potential for improvement in routine care are to be identified.

At inclusion, data in patient characteristics, comorbidities, clinical characteristics and previous treatments, if applicable, are collected. During the course of observation data on all systemic treatments, radiotherapies, surgeries, and clinical outcome are documented.

Health-realted quality of life in patients with hematological malignancies will be evaluated for up to one year.

Registry Platform Hematologic Malignancies (RUBIN) - Extension of Tumor Registry Lymphatic Neoplasms

Clinical Research Platform on Treatment, Quality of Life and Outcome of Patients With Hematologic Malignancies (RUBIN) - Extension of Tumor Registry Lymphatic Neoplasms

Documentation of anamnestic data and therapy sequences. Documentation of anamnestic data and therapy sequences

Documentation of response rates per line of treatment.

Documentation of progression-free survival per line of treatment.

iOMEDICO AG

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Zanubrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity

Study Director

This was a single-arm, multicenter Phase 2 study in Chinese participants with relapsed or refractory Waldenström's macroglobulinemia who exhibited one or more of the criteria for requiring treatment based on consensus guidelines from the Seventh International Workshop on Waldenström's Macroglobulinemia (IWWM). The study comprised an initial screening phase (up to 28 days), a single-arm treatment phase, and a follow-up phase.

Study of BTK Inhibitor BGB-3111 in Chinese Subjects With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)

A Phase 2, Single-Arm, Open-Label, Multicenter Study of Bruton's Tyrosine Kinase (BTK) Inhibitor BGB-3111 in Chinese Subjects With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)

MRR is defined as the percentage of participants who achieved complete response (CR) + very good partial response (VGPR) + partial response (PR), as assessed by an independent review committee according to modified Owen's criteria

PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by an independent review committee using modified Owen's criteria

Progression/death event-free rates were estimated by Kaplan-Meier method with 95% confidence intervals (CIs) estimated using Greenwood's formula

ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response, as assessed by an independent review committee using modified Owen's criteria

DOMR is defined as the time from the date that the major response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever comes first, as assessed by an independent review committee using modified Owen's criteria

DOMR event-free rates were estimated by Kaplan-Meier method with 95% CIs estimated using Greenwood's formula

Number of participants with resolution of treatment-precipitating symptoms, defined as any resolution (from "Yes" at baseline to "No" at any postbaseline point onwards during study) of the indications for initiation of therapy in WM signs and symptoms evaluation.

Number of participants with an anti-lymphoma effect, defined as any reduction during the course of study in bone marrow involvement by lymphoplasmacytoid lymphocytes and/or size of lymphadenopathy and/or splenomegaly by computed tomography scan as assessed by an independent review committee; lymphadenopathy is defined as any node with longest diameter (LDi) \> 1.5 cm and splenomegaly is defined as vertical spleen length \> 13 cm

Number of participants with treatment-emergent adverse events (TEAEs), grade 3 or higher TEAEs, serious adverse events (SAEs), treatment-related adverse events (AEs), adverse events of special interest, and TEAEs leading to study drug discontinuation, dose reduction and treatment interruption

BeiGene

A treatment-emergent adverse event (TEAE) was defined as an adverse event that had an onset or worsening in severity from baseline (pretreatment) on or after the date of first dose of study drug up to 30 days after the last dose of study drug or initiation of new anticancer therapy, whichever occurred first. Worsening of an event to Grade 5 beyond 30 days after the last dose of study drug was also considered a TEAE (if prior to start of new anticancer therapy).

Age, Continuous

Sex: Female, Male

Chinese

Race/Ethnicity, Customized

Zanubrutinib versus historical control estimate of 30%

Efficacy Analysis Set includes participants with confirmed Waldenström's macroglobulinemia based on central pathologic review among those who received at least one dose of study drug and with a baseline IgM (or M-protein) ≥ 5 g/L

Major Response Rate (MRR) as Assessed by the Independent Review Committee

Progression Free Survival (PFS)

6 months

9 months

12 months

PFS: Event-free Rate

Overall Response Rate (ORR)

Duration of Major Response (DOMR)

DOMR: Event-free Rate

Number of Participants With Resolution of Treatment-precipitating Symptoms

Number of Participants With an Anti-lymphoma Effect

At least one TEAE

Grade 3 or higher TEAEs

Serious TEAEs

Treatment-related TEAEs

TEAEs of special interest

TEAEs leading to study drug discontinuation

TEAEs leading to treatment interruption

TEAEs leading to dose reduction

The Safety Analysis Set included all participants who received ≥ 1 dose of study drug

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Evaluate Adverse Events, Change in Disease Activity, Movement of Oral ABBV-623 and ABBV-992 Tablets in the Body of Adult Participants With B-cell Cancers	NCT04804254	B-cell Lymphoma	ABBV-623 ABBV-992	18 Years -	AbbVie
Registry Platform Hematologic Malignancies (RUBIN) - Extension of Tumor Registry Lymphatic Neoplasms	NCT06043011	Chronic Lymphoc... Diffuse Large B... Follicular Lymp... Mantle Cell Lym... Marginal Zone L... Waldenström's M...	Routine care as...	18 Years -	iOMEDICO AG
Study of BTK Inhibitor BGB-3111 in Chinese Subjects With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)	NCT03332173	Waldenström's M...	Zanubrutinib	18 Years -	BeiGene
Study to Evaluate Adverse Events, Change in Disease Activity, Movement of Oral ABBV-623 and ABBV-992 Tablets in the Body of Adult Participants With B-cell Cancers	NCT04804254	B-cell Lymphoma	ABBV-623 ABBV-992	18 Years -	AbbVie

Spots Global Cancer Trial Database for waldenström's macroglobulinemia (wm)