Overview

This trial is active, not recruiting.

Condition relapsed/refractory multiple myeloma
Treatments abt-199, bortezomib, dexamethasone
Phase phase 1
Targets BCL-2, proteasome
Sponsor AbbVie (prior sponsor, Abbott)
Collaborator Genentech, Inc.
Start date November 2012
End date January 2017
Trial size 66 participants
Trial identifier NCT01794507, 2011-004626-10, M12-901

Summary

The primary objectives of this study are to assess the safety profile, characterize pharmacokinetics (PK) and determine the dosing schedule, maximum tolerated dose (MTD), and the recommended phase two dose (RPTD) of ABT-199 when administered in subjects with relapsed /refactory multiple myeloma who are receiving bortezomib and dexamethasone as their standard therapy.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Evaluate the safety and pharmacokinetics profile of ABT-199 administered with standard therapy bortezomib and dexamethasone in a dose escalation scheme in approximately 18 subjects.
abt-199
ABT-199 at cohort-defined dosing schedules and dose levels. ABT-199 at defined dose and schedule for Safety Expansion cohort
bortezomib
Bortezomib at cohort-defined dosing schedules and dose levels. Bortezomib at defined dose and schedule for Safety Expansion cohort
dexamethasone
Dexamethasone at cohort-defined dosing schedules and dose levels. Dexamethasone at defined dose and schedule for Safety Expansion cohort.
(Experimental)
Safety expansion cohort to further evaluate recommended phase two dose (RPTD) of ABT-199 administered with standard therapy bortezomib and dexamethasone in approximately 12 subjects.
abt-199
ABT-199 at cohort-defined dosing schedules and dose levels. ABT-199 at defined dose and schedule for Safety Expansion cohort
bortezomib
Bortezomib at cohort-defined dosing schedules and dose levels. Bortezomib at defined dose and schedule for Safety Expansion cohort
dexamethasone
Dexamethasone at cohort-defined dosing schedules and dose levels. Dexamethasone at defined dose and schedule for Safety Expansion cohort.

Primary Outcomes

Measure
Number and percentage of subjects with adverse events
time frame: From subject's first dose of ABT-199 until 30 days after subject's last dose of ABT-199; up to 2 years following last subject first dose.
Change in physical exam findings, including vital signs
time frame: From subject's baseline (prior to subject's first dose) assessed up to 2 years following the last subject first dose.
Determine dosing schedule, maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of ABT-199
time frame: Minimum first cycle of dosing (21 days) plus any lead-in period dosing (if used)
Change in clinical laboratory test results
time frame: From subject's baseline (prior to subject's first dose) assessed up to 2 years following the last subject first dose.
Change in cardiac assessment findings
time frame: From subject's baseline (prior to subject's first dose) assessed up to 2 years following the last subject first dose.
Determination of peak concentration (Cmax), trough concentration (Ctrough) and area under the concentration versus time curve (AUC) of ABT-199
time frame: Dose Escalation: Once on Lead-in D1; 5 times on Lead-in D7; twice on Cycle 1 D1; 5 times C1 D11; once on C1 D12 & on Day 1 of Cycles 2, 4, 6 & 8. Safety Exp: Once on Lead-in Day1; 5 times Cycle 1 D1; once on Cycle 1 D2 & on Day 1 of Cycles 2, 4, 6 & 8.

Secondary Outcomes

Measure
Exploratory pharmacodynamic studies: Change in bone marrow aspirate and core biopsy samples for Cytogenetics/FISH, Bcl-2 Family Member mRNA Analysis, Bcl-2 Family Member Protein Analysis
time frame: From subject's baseline (prior to subject's first dose) assessed up to 2 years following the last subject first dose.
Calculation of Objective Response Rate
time frame: Measured at Day 0, Cycle 3 Day 1, Cycle 5 Day 1, Cycle 9 Day 1 and Day 1 every other Cycle thereafter (e.g., 11, 13, 15, etc.) up to 48 months
Calculation of Time to Disease Progression
time frame: Measured at Day 0, Cycle 3 Day 1, Cycle 5 Day 1, Cycle 9 Day 1 and Day 1 every other Cycle thereafter (e.g., 11, 13, 15, etc.) up to 48 months
Calculation of Duration of Response
time frame: Measured at Day 0, Cycle 3 Day 1, Cycle 5 Day 1, Cycle 9 Day 1 and Day 1 every other Cycle thereafter (e.g., 11, 13, 15, etc.) up to 48 months
Exploratory pharmacodynamic studies: Change in Serum Markers and Plasma Markers Blood Samples
time frame: From subject's baseline (prior to subject's first dose) assessed up to 2 years following the last subject first dose.
Exploratory pharmacogenetic study: Evaluate blood samples to define relationship between drug concentration and disease status
time frame: Screening (prior to subject's first dose)

Eligibility Criteria

Male or female participants from 18 years up to 99 years old.

Inclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 1 - Diagnosis of multiple myeloma previously treated with at least 1 prior line of therapy (dose escalation only) or (safety expansion only) received treatment with a proteasome inhibitor or an IMiD(r) or immunomodulatory agent (e.g., thalidomide, lenalidomide). Induction therapy and following stem cell transplant are considered a single line of therapy. - Measurable disease at Screening: Serum monoclonal protein greater than or equal to 1 g/dL by protein electrophoresis, or greater than or equal to 200 mg monoclonal protein in the urine on 24-hr electrophoresis, or serum immunoglobulin free light chain greater than or equal to 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio. - Subject has a history of autologous or allogenic stem cell transplant, have adequate bone marrow independent of any growth factor support, and have recovered from any transplant related toxicity(s); and either greater than 100 days post-autologous transplant (prior to first dose of study drug) or greater than or equal to 6 months post-allogenic transplant (prior to first dose of study drug) and not have active graft-versus-host disease (i.e., requiring treatment). - Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening. Exclusion Criteria: - Exhibits evidence of other clinically significant uncontrolled condition(s), including, but not limited to: uncontrolled systemic infection (viral, bacterial, or fungal), diagnosis of fever and neutropenia within 1 week prior to first dose of study drug - Cardiovascular disability status of New York Heart Association Class greater than 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea or anginal pain. - Significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, pulmonary or hepatic disease, that in the opinion of the investigator, would adversely affect his/her participation in the study. - History of other active malignancies other than multiple myeloma within the past 3 years prior to study entry, with the following exceptions: adequately treated in situ carcinoma of the cervix uteri, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. - Tested positive for HIV or hepatitis.

Additional Information

Official title A Phase 1b Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Relapsed or Refractory Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Their Standard Therapy
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by AbbVie.