A Study of Venetoclax and ABBV-838 Combination Therapy With Dexamethasone in Participants With Multiple Myeloma Whose Cancer Has Come Back or Had No Response to Recent Cancer Treatment

NCT ID: NCT02951117

Last Updated: 2017-06-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-31
• Study Completion Date: 2021-04-28

Brief Summary

This is an open-label, multicenter clinical trial designed to evaluate the safety and potential efficacy of venetoclax and ABBV-838 combination therapy with dexamethasone in participants with relapsed or refractory multiple myeloma (MM) who have received 2 or more prior lines of therapy for multiple myeloma (MM). The study will consist of 2 arms: Arm A and Arm B (if applicable). Each arm will have a dose escalation and dose expansion portion.

Detailed Description

The study will consist of 2 arms: Arm A and Arm B (if applicable). Arm A dose escalation will investigate up to 3 doses of ABBV-838 at 3-week dosing intervals (Q3W) in combination with venetoclax and dexamethasone. Arm A dose expansion portion will investigate the ABBV-838 Q3W dosing interval with venetoclax and dexamethasone at the recommended phase two dose (RPTD) combination defined from the Dose Escalation portion.

Based on data from the ongoing ABBV-838 monotherapy study (Study M14-467) Arm B dose escalation may be conducted, if deemed necessary. If conducted, Arm B dose excalation will investigate up to 3 doses of ABBV-838 at either weekly (Q1W) or bi-weekly (Q2W) dosing intervals in combination with venetoclax and dexamethasone. Arm B dose expansion portion will investigate either the ABBV-838 Q1W or Q2W dosing interval in combination with venetoclax and dexamethasone at the RPTD combination defined from the Dose Escalation portion.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A Venetoclax QD + ABBV-838 Q3W + Dexamethasone

ABBV-838 administered at cohort-defined doses every 3 weeks (Q3W; starting dose 4.0 mg/kg) in combination with venetoclax (400 mg or 800 mg once daily \[QD\]) and dexamethasone (40 mg once weekly \[Q1W\]); once the maximum-tolerated-dose (MTD) and recommended phase two dose (RPTD) are determined, ABBV-838 in combination with venetoclax and dexamethasone at RPTD will be administered in a dose expansion phase of the study.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Tablet

ABBV-838

Intervention Type: DRUG

Intravenous infusion

Dexamethasone

Intervention Type: DRUG

Tablet or intravenous infusion

Arm B Venetoclax QD + ABBV-838 Q1W or Q2W + Dexamethasone Q1W

Dose escalation portion will investigate either the ABBV-838 weekly (Q1W) or bi-weekly (Q2W) dosing interval in combination with venetoclax (400 or 800 mg QD) and dexamethasone (40 mg Q1W).

The dose expansion portion will investigate either the ABBV-838 weekly (Q1W) or bi-weekly (Q2W) dosing interval in combination with venetoclax and dexamethasone at the RPTD combination defined from the Dose Escalation portion.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Tablet

ABBV-838

Intervention Type: DRUG

Intravenous infusion

Dexamethasone

Intervention Type: DRUG

Tablet or intravenous infusion

Interventions

Venetoclax

Tablet

Intervention Type: DRUG

ABBV-838

Intravenous infusion

Intervention Type: DRUG

Dexamethasone

Tablet or intravenous infusion

Intervention Type: DRUG

Other Intervention Names

ABT-199

Eligibility Criteria

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 for participants in the dose escalation portion of the study and ECOG less than or equal to 2 in the dose expansion portion.
• Received at least 2 prior therapies including an Immunomodulatory Thalidomide Derivative Compounds (IMiD) and a proteasome inhibitor.
• Documented relapsed or progressive multiple myeloma on or after any regimen or is refractory to the most recent line of therapy.
• Received at least 2 prior therapies including an IMiD and a proteasome inhibitor.
• Documented relapsed or progressive multiple myeloma on or after any regimen or is refractory to the most recent line of therapy.
• Eligible for and agree to bone marrow (BM) aspirate prior to treatment start and at designated times per protocol.
• Measurable disease at Screening, defined as at least one of the following M component in serum (greater than or equal to 0.5 g/dL) and/or urine (greater than or equal to 0.2 g excreted in a 24 hour collection sample) or serum free light chain greater than or equal to 100 mg/dL with an abnormal κ/λ ratio of less than 0.26 or greater than 1.65.

Exclusion Criteria

• Received any anti-myeloma therapy (other than monoclonal antibodies), including chemotherapy, radiotherapy, biological, immunotherapy or an investigational therapy, including targeted small molecule agents within 5 half-lives (or 14 days if half-live unknown) prior to first dose of first dose of venetoclax, ABBV-838, and dexamethasone.
• Received anti-myeloma monoclonal antibodies within 6 weeks prior to first dose of venetoclax, ABBV-838, and dexamethasone.
• Has a significant history of renal, neurologic (peripheral neuropathy), psychiatric, endocrinologic (diabetes mellitus), metabolic, immunologic, cardiovascular, pulmonary or hepatic disease within the last 6 months.
• Received corticosteroid therapy at a dose equivalent to greater than or equal to 4 mg/day of dexamethasone within 3 weeks prior to first dose.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Orlando Bueno, MD

Role: STUDY_DIRECTOR

AbbVie

Locations

St Vincent´s Hospital /ID# 153022

Darlinghurst, , Australia

St. Vincents Hospital Melbourne /ID# 157925

Fitzroy, , Australia

The Alfred Hospital /ID# 150202

Prahran, , Australia

Countries

Australia

Other Identifiers

2016-001300-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M15-655

Identifier Type: -

Identifier Source: org_study_id