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 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: M20-2082020-005196-12
• Study Type: interventional
• Target: 5
• Locations: 3 countries
• Sites: 5

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.

Conditions

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

Outcome Measures

Primary Outcomes (6)

• 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.

  Up to approximately 25 months.

• 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.

  Up to approximately 96 weeks

• 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.

  Up to approximately 96 weeks

• 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.

  Up to approximately 96 weeks.

• 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.

  Up to approximately 96 weeks

• 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.

  Up to approximately 2 years

Secondary Outcomes (13)

• 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)

  Up to approximately 2 years

• Dose Escalation in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better

  Up to approximately 2 years

• Dose Escalation in Participants With R/R B-cell Malignancies: Time to Response (TTR)

  Up to approximately 2 years

• Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Achievement of a Response of PR or Better

  Up to approximately 2 years

• Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better

  Up to approximately 2 years

Study Arms (6)

Monotherapy in Dose Escalation: ABBV-623

EXPERIMENTAL

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

Drug: ABBV-623

Monotherapy in Dose Escalation: ABBV-992

EXPERIMENTAL

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

Drug: ABBV-992

Combination in Dose Escalation

EXPERIMENTAL

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

Drug: ABBV-623; Drug: ABBV-992

Monotherapy in Dose Expansion: ABBV-623

EXPERIMENTAL

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

Drug: ABBV-623

Monotherapy in Dose Expansion: ABBV-992

EXPERIMENTAL

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

Drug: ABBV-992

Combination in Dose Expansion

EXPERIMENTAL

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.

Drug: ABBV-623; Drug: ABBV-992

Interventions

ABBV-623 DRUG

Oral Tablets

Combination in Dose Escalation; Combination in Dose Expansion; Monotherapy in Dose Escalation: ABBV-623; Monotherapy in Dose Expansion: ABBV-623

ABBV-992 DRUG

Oral Tablets

Combination in Dose Escalation; Combination in Dose Expansion; Monotherapy in Dose Escalation: ABBV-992; Monotherapy in Dose Expansion: ABBV-992

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• AbbVie: lead

Study Sites (5)

The Chaim Sheba Medical Center /ID# 226754

Ramat Gan, Tel Aviv, 5265601, Israel

Location

Tel Aviv Sourasky Medical Center /ID# 226755

Tel Aviv, Tel Aviv, 6423906, Israel

Location

Hospital del Centro Comprensivo de Cancer de la UPR /ID# 225646

San Juan, 00927, Puerto Rico

Location

Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 226087

Ankara, 06200, Turkey (Türkiye)

Location

Dokuz Eylul University Medical Faculty /ID# 226085

Izmir, 35340, Turkey (Türkiye)

Location

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: March 18, 2021
• Study Start: April 27, 2021
• Primary Completion: January 11, 2023
• Study Completion: January 11, 2023
• Last Updated: February 3, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2); TU (2); PR (1)