Clinical Trials /

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

Description:

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.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Small Lymphocytic Lymphoma
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: M20-208
  • SECONDARY ID: 2020-005196-12
  • NCT ID: NCT04804254

Conditions

  • B-cell Lymphoma

Interventions

DrugSynonymsArms
ABBV-623Combination in Dose Escalation
ABBV-992Combination in Dose Escalation

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Monotherapy in Dose Escalation: ABBV-623ExperimentalParticipants with Relapsed/Refractory (R/R) B-cell malignancies will receive escalating doses of ABBV-623.
  • ABBV-623
Monotherapy in Dose Escalation: ABBV-992ExperimentalParticipants with R/R B-cell malignancies will receive escalating doses of ABBV-992.
  • ABBV-992
Combination in Dose EscalationExperimentalParticipants with R/R B-cell malignancies will receive escalating doses of ABBV-623 and ABBV-992.
  • ABBV-623
  • ABBV-992
Monotherapy in Dose Expansion: ABBV-623ExperimentalParticipants with R/R B-cell malignancies will receive ABBV-623 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.
  • ABBV-623
Monotherapy in Dose Expansion: ABBV-992ExperimentalParticipants with R/R B-cell malignancies will receive ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.
  • ABBV-992
Combination in Dose ExpansionExperimentalParticipants 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

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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Adverse Events (AEs)
Time Frame:Up to approximately 25 months.
Safety Issue:
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.

Secondary Outcome Measures

Measure: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)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Partial response (PR) as per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) , Lugano, International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria in protocol.
Measure:Dose Escalation in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better
Time Frame:Up to approximately 2 years
Safety Issue:
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.
Measure:Dose Escalation in Participants With R/R B-cell Malignancies: Time to Response (TTR)
Time Frame:Up to approximately 2 years
Safety Issue:
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.
Measure:Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Achievement of a Response of PR or Better
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Partial response (PR) as per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) , Lugano, International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria in protocol.
Measure:Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better
Time Frame:Up to approximately 2 years
Safety Issue:
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.
Measure:Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Time to Response (TTR)
Time Frame:Up to approximately 2 years
Safety Issue:
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.
Measure:Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)
Time Frame:Up to approximately 6 months
Safety Issue:
Description:Undetectable minimal residual disease (uMRD) is described as less than one myeloma cell per million bone marrow cells.
Measure:Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)
Time Frame:Up to approximately 1 Year
Safety Issue:
Description:Undetectable minimal residual disease (uMRD) is described as less than one myeloma cell per million bone marrow cells.
Measure:Combination Dose Expansion in Participants With CLL/SLL: Percentage of Participants With Achievement of Peripheral Blood uMRD
Time Frame:Up to approximately 96 weeks
Safety Issue:
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.
Measure:Combination Dose Expansion in Participants With CLL/SLL: Duration of Response for Participants With a Response of PR or Better
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Duration of response is defined as the time from the initial objective response to disease progression or death, whichever occurs first.
Measure:Combination Dose Expansion in Participants With CLL/SLL: Time to Response
Time Frame:Up to approximately 2 years
Safety Issue:
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.
Measure:Combination Dose Expansion in Participants with CLL/SLL: Progression Free Survival
Time Frame:Approximately 2 years after study drug discontinuation
Safety Issue:
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.
Measure:Combination Dose Expansion in Participants With CLL/SLL: Overall Survival
Time Frame:Approximately 2 years after study drug discontinuation
Safety Issue:
Description:Overall Survival is defined as the number of days from the date the participant was randomized to the date of death.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AbbVie

Trial 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

Last Updated

May 27, 2021