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

NCT02951117 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: M15-6552016-001300-28
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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.

Conditions

Multiple Myeloma

Keywords

lymphoid malignancies; Next generation sequencing; Refractory Multiple Myeloma; Relapsed Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of venetoclax and ABBV-838 combination therapy when administered with dexamethasone

  The MTD and the RPTD of venetoclax and ABBV-838 combination therapy with dexamethasone will be determined during the dose escalation phase of the study. Once the RPTD combination has been determined, the dose expansion portion will begin.

  Minimum first cycle of dosing (21 or 28 days, depending on arm)

• Number of participants with adverse events

  Up to approximately 2 years following the first dose of the last subject enrolled

Secondary Outcomes (12)

• Maximum observed plasma concentration (Cmax) of venetoclax

  Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

• Time to Cmax (Tmax) of venetoclax

  Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

• Area under the plasma concentration-time curve over the 24-hour dose interval (AUC0-24) of venetoclax

  Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

• Objective Response Rate (ORR)

  Cycle 2 Day 1 and Day 1 of every cycle thereafter for up to 2 years following the first dose of the last subject enrolled

• Cmax of ABBV-838

  Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

Study Arms (2)

Arm A Venetoclax QD + ABBV-838 Q3W + Dexamethasone

EXPERIMENTAL

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.

Drug: Venetoclax; Drug: ABBV-838; Drug: Dexamethasone

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

EXPERIMENTAL

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.

Drug: Venetoclax; Drug: ABBV-838; Drug: Dexamethasone

Interventions

Venetoclax DRUG

Tablet

Also known as: ABT-199

Arm A Venetoclax QD + ABBV-838 Q3W + Dexamethasone; Arm B Venetoclax QD + ABBV-838 Q1W or Q2W + Dexamethasone Q1W

ABBV-838 DRUG

Intravenous infusion

Arm A Venetoclax QD + ABBV-838 Q3W + Dexamethasone; Arm B Venetoclax QD + ABBV-838 Q1W or Q2W + Dexamethasone Q1W

Dexamethasone DRUG

Tablet or intravenous infusion

Arm A Venetoclax QD + ABBV-838 Q3W + Dexamethasone; Arm B Venetoclax QD + ABBV-838 Q1W or Q2W + Dexamethasone Q1W

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (3)

St Vincent´s Hospital /ID# 153022

Darlinghurst, 2010, Australia

Location

St. Vincents Hospital Melbourne /ID# 157925

Fitzroy, 3065, Australia

Location

The Alfred Hospital /ID# 150202

Prahran, 3181, Australia

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

venetoclax; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Orlando Bueno, MD

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2016
• First Posted: November 1, 2016
• Study Start: August 31, 2017
• Primary Completion: July 28, 2020
• Study Completion: April 28, 2021
• Last Updated: June 5, 2017

Record last verified: 2017-06

Locations

AU (3)