Back to resultsStudy 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
Primary Purpose
B-cell Lymphoma
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ABBV-623
ABBV-992
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Lymphoma focused on measuring ABBV-623, ABBV-992, B-cell lymphoma, Cancer, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Waldenström's Macroglobulinemia (WM), Diffuse Large B-cell Lymphoma, Follicular Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Participants must have documented diagnosis for one of the following B-cell malignancies: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Waldenström's macroglobulinemia (WM), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), with measurable disease requiring treatment.
- Participants have relapsed or refractory to at least 2 prior systemic therapies.
- Combination Dose Expansion Only: Participants with documented diagnosis of CLL/SLL with measurable disease requiring treatment per by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- CLL/SLL, MCL, WM, MZL only: Prior Bruton's tyrosine kinase inhibitor (BTKi) exposure will be allowed if participant did not progress on active treatment and there is no evidence of resistance mutations.
- Renal, liver and hematological function lab values as determined in the protocol.
- For participants with prior BTK inhibitor exposure, no evidence of mutations which confer resistance to covalent BTK inhibitors.
Exclusion Criteria:
- Participants with indolent forms of non-Hodgkin lymphoma (NHL) that require immediate cytoreduction.
- Participants with prior B-cell lymphoma 2 (BCL2) inhibitor (BCL2i) exposure (except for participants in the ABBV-992 monotherapy cohort).
Sites / Locations
- The Chaim Sheba Medical Center /ID# 226754
- Tel Aviv Sourasky Medical Center /ID# 226755
- Hospital del Centro Comprensivo de Cancer de la UPR /ID# 225646
- Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 226087
- Dokuz Eylul University Medical Faculty /ID# 226085
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Monotherapy in Dose Escalation: ABBV-623
Monotherapy in Dose Escalation: ABBV-992
Combination in Dose Escalation
Monotherapy in Dose Expansion: ABBV-623
Monotherapy in Dose Expansion: ABBV-992
Combination in Dose Expansion
Arm Description
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.
Outcomes
Primary Outcome Measures
Percentage of Participants With Adverse Events (AEs)
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.
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-623
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.
Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-623
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.
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-992
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.
Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-992
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.
Combination Dose Expansion: Overall Response Rate (ORR) (PR or Better by IWCLL Criteria) in Participants With R/R CLL/SLL
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.
Secondary Outcome Measures
Dose Escalation in Participants With R/R B-cell Malignancies: Percentage of Participants Achieving a Response of Partial Response (PR) or Better per Disease-Specific Response Criteria (e.g., IWCLL, Lugano, IWWM)
Partial response (PR) as per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) , Lugano, International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria in protocol.
Dose Escalation in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better
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.
Dose Escalation in Participants With R/R B-cell Malignancies: Time to Response (TTR)
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.
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Achievement of a Response of PR or Better
Partial response (PR) as per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) , Lugano, International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria in protocol.
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better
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.
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Time to Response (TTR)
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.
Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)
Undetectable minimal residual disease (uMRD) is described as less than one myeloma cell per million bone marrow cells.
Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)
Undetectable minimal residual disease (uMRD) is described as less than one myeloma cell per million bone marrow cells.
Combination Dose Expansion in Participants With CLL/SLL: Percentage of Participants With Achievement of Peripheral Blood uMRD
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.
Combination Dose Expansion in Participants With CLL/SLL: Duration of Response for Participants With a Response of PR or Better
Duration of response is defined as the time from the initial objective response to disease progression or death, whichever occurs first.
Combination Dose Expansion in Participants With CLL/SLL: Time to Response
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.
Combination Dose Expansion in Participants with CLL/SLL: Progression Free Survival
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.
Combination Dose Expansion in Participants With CLL/SLL: Overall Survival
Overall Survival is defined as the number of days from the date the participant was randomized to the date of death.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04804254
Brief Title
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
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
Strategic considerations
Study Start Date
April 27, 2021 (Actual)
Primary Completion Date
January 11, 2023 (Actual)
Study Completion Date
January 11, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Lymphoma
Keywords
ABBV-623, ABBV-992, B-cell lymphoma, Cancer, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Waldenström's Macroglobulinemia (WM), Diffuse Large B-cell Lymphoma, Follicular Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Monotherapy in Dose Escalation: ABBV-623
Arm Type
Experimental
Arm Description
Participants with Relapsed/Refractory (R/R) B-cell malignancies will receive escalating doses of ABBV-623.
Arm Title
Monotherapy in Dose Escalation: ABBV-992
Arm Type
Experimental
Arm Description
Participants with R/R B-cell malignancies will receive escalating doses of ABBV-992.
Arm Title
Combination in Dose Escalation
Arm Type
Experimental
Arm Description
Participants with R/R B-cell malignancies will receive escalating doses of ABBV-623 and ABBV-992.
Arm Title
Monotherapy in Dose Expansion: ABBV-623
Arm Type
Experimental
Arm Description
Participants with R/R B-cell malignancies will receive ABBV-623 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.
Arm Title
Monotherapy in Dose Expansion: ABBV-992
Arm Type
Experimental
Arm Description
Participants with R/R B-cell malignancies will receive ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.
Arm Title
Combination in Dose Expansion
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ABBV-623
Intervention Description
Oral Tablets
Intervention Type
Drug
Intervention Name(s)
ABBV-992
Intervention Description
Oral Tablets
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (AEs)
Description
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.
Time Frame
Up to approximately 25 months.
Title
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-623
Description
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.
Time Frame
Up to approximately 96 weeks
Title
Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-623
Description
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.
Time Frame
Up to approximately 96 weeks
Title
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-992
Description
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.
Time Frame
Up to approximately 96 weeks.
Title
Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-992
Description
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.
Time Frame
Up to approximately 96 weeks
Title
Combination Dose Expansion: Overall Response Rate (ORR) (PR or Better by IWCLL Criteria) in Participants With R/R CLL/SLL
Description
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.
Time Frame
Up to approximately 2 years
Secondary Outcome Measure Information:
Title
Dose Escalation in Participants With R/R B-cell Malignancies: Percentage of Participants Achieving a Response of Partial Response (PR) or Better per Disease-Specific Response Criteria (e.g., IWCLL, Lugano, IWWM)
Description
Partial response (PR) as per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) , Lugano, International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria in protocol.
Time Frame
Up to approximately 2 years
Title
Dose Escalation in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better
Description
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 Frame
Up to approximately 2 years
Title
Dose Escalation in Participants With R/R B-cell Malignancies: Time to Response (TTR)
Description
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.
Time Frame
Up to approximately 2 years
Title
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Achievement of a Response of PR or Better
Description
Partial response (PR) as per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) , Lugano, International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria in protocol.
Time Frame
Up to approximately 2 years
Title
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better
Description
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 Frame
Up to approximately 2 years
Title
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Time to Response (TTR)
Description
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.
Time Frame
Up to approximately 2 years
Title
Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)
Description
Undetectable minimal residual disease (uMRD) is described as less than one myeloma cell per million bone marrow cells.
Time Frame
Up to approximately 6 months
Title
Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)
Description
Undetectable minimal residual disease (uMRD) is described as less than one myeloma cell per million bone marrow cells.
Time Frame
Up to approximately 1 Year
Title
Combination Dose Expansion in Participants With CLL/SLL: Percentage of Participants With Achievement of Peripheral Blood uMRD
Description
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.
Time Frame
Up to approximately 96 weeks
Title
Combination Dose Expansion in Participants With CLL/SLL: Duration of Response for Participants With a Response of PR or Better
Description
Duration of response is defined as the time from the initial objective response to disease progression or death, whichever occurs first.
Time Frame
Up to approximately 2 years
Title
Combination Dose Expansion in Participants With CLL/SLL: Time to Response
Description
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.
Time Frame
Up to approximately 2 years
Title
Combination Dose Expansion in Participants with CLL/SLL: Progression Free Survival
Description
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.
Time Frame
Approximately 2 years after study drug discontinuation
Title
Combination Dose Expansion in Participants With CLL/SLL: Overall Survival
Description
Overall Survival is defined as the number of days from the date the participant was randomized to the date of death.
Time Frame
Approximately 2 years after study drug discontinuation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants must have documented diagnosis for one of the following B-cell malignancies: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Waldenström's macroglobulinemia (WM), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), with measurable disease requiring treatment.
Participants have relapsed or refractory to at least 2 prior systemic therapies.
Combination Dose Expansion Only: Participants with documented diagnosis of CLL/SLL with measurable disease requiring treatment per by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria.
Eastern Cooperative Oncology Group performance status of 0 or 1.
CLL/SLL, MCL, WM, MZL only: Prior Bruton's tyrosine kinase inhibitor (BTKi) exposure will be allowed if participant did not progress on active treatment and there is no evidence of resistance mutations.
Renal, liver and hematological function lab values as determined in the protocol.
For participants with prior BTK inhibitor exposure, no evidence of mutations which confer resistance to covalent BTK inhibitors.
Exclusion Criteria:
Participants with indolent forms of non-Hodgkin lymphoma (NHL) that require immediate cytoreduction.
Participants with prior B-cell lymphoma 2 (BCL2) inhibitor (BCL2i) exposure (except for participants in the ABBV-992 monotherapy cohort).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ABBVIE INC.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
The Chaim Sheba Medical Center /ID# 226754
City
Ramat Gan
State/Province
Tel-Aviv
ZIP/Postal Code
5265601
Country
Israel
Facility Name
Tel Aviv Sourasky Medical Center /ID# 226755
City
Tel Aviv-Yafo
State/Province
Tel-Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Hospital del Centro Comprensivo de Cancer de la UPR /ID# 225646
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico
Facility Name
Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 226087
City
Ankara
ZIP/Postal Code
06200
Country
Turkey
Facility Name
Dokuz Eylul University Medical Faculty /ID# 226085
City
Izmir
ZIP/Postal Code
35340
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this 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
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