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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02462525
• Other study ID #: M14-467
• Secondary ID: 2014-002609-39
• Status: Terminated
• Phase: Phase 1
• Start date: May 6, 2015
• Est. completion date: December 6, 2017

Study information

• Verified date: September 2018
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 74
• Est. completion date: December 6, 2017
• Est. primary completion date: December 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• ABBV-838
Varying doses of ABBV-838
• Pomalidomide
Administered orally per the label.
• Dexamethasone
Administered orally per the label.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration (Cmax) of ABBV-838	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
Primary	Maximum tolerated dose of ABBV-838	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	Preliminary activity of ABBV-838 monotherapy	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