Dose-Escalation Study of ABBV-838, an Antibody Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT02462525
- Lead Sponsor
- AbbVie
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 74
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ABBV-838 plus pomalidomide/dexamethasone ABBV-838 ABBV-838 to be evaluated with pomalidomide/dexamethasone. ABBV-838 dose escalation ABBV-838 Varying doses of ABBV-838 ABBV-838 plus pomalidomide/dexamethasone Dexamethasone ABBV-838 to be evaluated with pomalidomide/dexamethasone. ABBV-838 plus pomalidomide/dexamethasone Pomalidomide ABBV-838 to be evaluated with pomalidomide/dexamethasone.
- Primary Outcome Measures
Name Time Method Maximum tolerated dose of ABBV-838 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.
Maximum plasma concentration (Cmax) of ABBV-838 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.
- Secondary Outcome Measures
Name Time Method Preliminary activity of ABBV-838 monotherapy 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.
Trial Locations
- Locations (19)
Washington University School of Medicine /ID# 135708
🇺🇸Saint Louis, Missouri, United States
Mount Sinai Medical Center /ID# 133569
🇺🇸New York, New York, United States
The University of Chicago Medical Center /ID# 139403
🇺🇸Chicago, Illinois, United States
Universitaetsklinikum Wuerzburg /ID# 141533
🇩🇪Wuerzburg, Germany
Universitaetsklinikum Schleswig-Holstein /ID# 141534
🇩🇪Kiel, Germany
Universitaetsklinikum Heidelberg /ID# 140046
🇩🇪Heidelberg, Germany
Clinica Universitaria de Navarra /ID# 141411
🇪🇸Pamplona-Navarra, Spain
Hospital Universitario 12 de Octubre /ID# 140878
🇪🇸Madrid, Spain
Hospital Universitario de la Princesa /ID# 140881
🇪🇸Madrid, Spain
Hospital Clinic de Barcelona /ID# 141643
🇪🇸Barcelona, Spain
Hospital Clinico Universitario Salamanca /ID# 140880
🇪🇸Salamanca, Spain
CHU de Nantes, Hotel Dieu - HME /ID# 133633
🇫🇷Nantes Cedex 1, France
Universitaetsklinikum Tuebingen /ID# 141074
🇩🇪Tuebingen, Germany
CHU de la miletrie, Centre d'investigation clinique /ID# 147542
🇫🇷Poitiers, France
CHRU de Lille, Hopital Claude Huriez /ID# 133634
🇫🇷Lille Cedex, France
Universitaetsklinikum Koeln /ID# 141535
🇩🇪Cologne, Germany
Universitaetklinikum Dresden /ID# 141860
🇩🇪Dresden, Germany
University of Michigan Medical Center /ID# 139402
🇺🇸Ann Arbor, Michigan, United States
The Sarah Cannon Research Institute /ID# 135814
🇺🇸Nashville, Tennessee, United States