Dose-Escalation Study of ABBV-838, an Antibody Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma

September 12, 2018 updated by: AbbVie

A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABBV-838, an Antibody Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma

This is a Phase 1/1b, open-label, dose-escalation study designed to evaluate the safety, pharmacokinetics, and to determine the recommended Phase 2 dose of ABBV-838 in subjects with relapsed and refractory multiple myeloma.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lille Cedex, France, 59037
        • CHRU de Lille, Hopital Claude Huriez /ID# 133634
      • Nantes Cedex 1, France, 44093
        • CHU de Nantes, Hotel Dieu - HME /ID# 133633
      • Poitiers, France, 86021
        • CHU de la miletrie, Centre d'investigation clinique /ID# 147542
  • Germany
      • Cologne, Germany, 50937
        • Universitaetsklinikum Koeln /ID# 141535
      • Dresden, Germany, 01307
        • Universitaetklinikum Dresden /ID# 141860
      • Heidelberg, Germany, 69210
        • Universitaetsklinikum Heidelberg /ID# 140046
      • Kiel, Germany, 24105
        • Universitaetsklinikum Schleswig-Holstein /ID# 141534
      • Tuebingen, Germany, 72076
        • Universitaetsklinikum Tuebingen /ID# 141074
      • Wuerzburg, Germany, 97080
        • Universitaetsklinikum Wuerzburg /ID# 141533
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona /ID# 141643
      • Madrid, Spain, 28006
        • Hospital Universitario de la Princesa /ID# 140881
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre /ID# 140878
      • Pamplona-Navarra, Spain, 31008
        • Clinica Universitaria de Navarra /ID# 141411
      • Salamanca, Spain, 37007
        • Hospital Clinico Universitario Salamanca /ID# 140880
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago Medical Center /ID# 139403
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Medical Center /ID# 139402
    • Missouri
      • Saint Louis, Missouri, United States, 63110-1093
        • Washington University School of Medicine /ID# 135708
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center /ID# 133569
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • The Sarah Cannon Research Institute /ID# 135814

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Eastern Cooperative Oncology Group Performance Status of 0 to 2
  • Not eligible for stem cell/bone marrow transplant or have refused stem cell/bone marrow transplant or have relapsed after autologous or allogeneic stem cell/bone marrow transplant
  • Eligible for and agree to BM aspirate prior to treatment start
  • Measurable disease M component in serum (≥ 0.5 g/dL) and/or urine (≥ 0.2 g excreted in a 24 hour collection sample)
  • Must have received at least 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or those who are double refractory to a PI and an immunomodulatory agent and have demonstrated disease progression (DP) on or within 60 days of completion of the last therapy; participants previously treated with an alkylating agent, in addition to an IMiD or proteasome inhibitor, are allowed to enroll in the trial
  • Participants must have adequate liver, kidney, and bone morrow function
  • Participants with a history of chronic heart failure must have cardiac ECHO indicating left ventricular ejection fraction (LVEF) ≥ 45% within 21 days prior to first dose of study drug
  • Participants in the combination therapy arms must be eligible to receive pomalidomide/dexamethasone, bortezomib/dexamethasone or lenalidomide/dexamethasone or other approved agents per current prescribing information for MM.
  • Participants who will receive combination therapy with Pomalidomide/Dexamethasone must have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy

Exclusion Criteria:

  • Received anti-cancer therapy including chemotherapy, immunotherapy, radiation, biologic, any investigational therapy or herbal therapy within a period of 21 days prior to the first dose of ABBV-838, and have unresolved toxicities ≥ grade 2
  • Concurrent metastatic solid tumors
  • Non-Measurable M Protein (serum or urine) and measurable sFLC (< 100 mg/mL)
  • Major surgery within 21 days prior to the first dose of ABBV-838
  • Clinically significant uncontrolled condition(s) including but not limited to the following:

Grade ≥ 3 peripheral neuropathy or grade 2 peripheral neuropathy with pain Uncontrolled hypercalcemia Active uncontrolled infection Symptomatic congestive heart failure Unstable angina pectoris or cardiac arrhythmia Psychiatric illness/social situation that would limit compliance with the study

  • Major immunologic reaction to any IgG containing agent or auristatin based agent
  • Participants who are taking strong CYP3A4 inhibitors
  • Positive for HIV (Human Immunodeficiency Virus) or with active hepatitis B and/or C
  • Corneal pathology that would limit evaluation of loss in visual acuity associated with corneal deposits.
  • Prior exposure to pomalidomide for subjects enrolling in the pomalidomide/dexamethasone combination arm.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: ABBV-838 dose escalation
Varying doses of ABBV-838
Drug: ABBV-838
Varying doses of ABBV-838
EXPERIMENTAL: ABBV-838 plus pomalidomide/dexamethasone
ABBV-838 to be evaluated with pomalidomide/dexamethasone.
Drug: ABBV-838
Varying doses of ABBV-838
Drug: Pomalidomide
Administered orally per the label.
Drug: Dexamethasone
Administered orally per the label.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum plasma concentration (Cmax) of ABBV-838
Time Frame: Cycle 1 Day 1 (C1D1) and C3D1 pre- and post-dose; C1D4, C1D8, C1D15, C2D1, C2D15, C3D4, C3D8, C3D15, C4D1, and all subsequent ABBV-838 pre-dose dosing cycles
The maximum plasma concentration (Cmax: measured in ng/ml) is the highest concentration that a drug achieves in the blood after the first dose, but before administration of a second dose.
Cycle 1 Day 1 (C1D1) and C3D1 pre- and post-dose; C1D4, C1D8, C1D15, C2D1, C2D15, C3D4, C3D8, C3D15, C4D1, and all subsequent ABBV-838 pre-dose dosing cycles
Maximum tolerated dose of ABBV-838
Time Frame: Up to 2 years from first dose of study
The highest dose level at which less than 2 of 6 subjects or less than 33% of (if cohort is expanded beyond 6) subjects experience a dose limiting toxicity.
Up to 2 years from first dose of study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preliminary activity of ABBV-838 monotherapy
Time Frame: At screening, Cycle 1 Day 15 (C1D15), C3D15, C4D1, and for subjects who have been on ABBV-838 for ≥ 6 cycles, radiologic tumor assessments may be performed every 3 cycles per Investigator discretion up to approximately 3 years
Response evaluation will be based on International Myeloma Working Group (IMWG) Response Criteria.
At screening, Cycle 1 Day 15 (C1D15), C3D15, C4D1, and for subjects who have been on ABBV-838 for ≥ 6 cycles, radiologic tumor assessments may be performed every 3 cycles per Investigator discretion up to approximately 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 6, 2015

Primary Completion (ACTUAL)

December 6, 2017

Study Completion (ACTUAL)

December 6, 2017

Study Registration Dates

First Submitted

May 26, 2015

First Submitted That Met QC Criteria

June 2, 2015

First Posted (ESTIMATE)

June 4, 2015

Study Record Updates

Last Update Posted (ACTUAL)

September 13, 2018

Last Update Submitted That Met QC Criteria

September 12, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M14-467
  • 2014-002609-39 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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