A Study Evaluating ABT-199 in Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Standard Therapy

Relapsed/Refractory Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01794507
• Other study ID #: M12-901
• Secondary ID: 2011-004626-10
• Status: Completed
• Phase: Phase 1
• Start date: November 19, 2012
• Est. completion date: July 16, 2019

Study information

• Verified date: July 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: July 16, 2019
• Est. primary completion date: July 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

• Subjects with a history of autologous or allogenic stem cell transplant must 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 or equal to 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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Ctr /ID# 79553	Melbourne	Victoria
Australia	Royal Melbourne Hospital /ID# 79533	Parkville	Victoria
France	CHRU Lille - Hôpital Claude Huriez /ID# 77234	Lille CEDEX	Hauts-de-France
France	CHU de Nantes, Hotel Dieu -HME /ID# 78773	Nantes
United States	University of Michigan Hospitals /ID# 80353	Ann Arbor	Michigan
United States	Northwestern University Feinberg School of Medicine /ID# 117477	Chicago	Illinois
United States	Mayo Clinic /ID# 121495	Jacksonville	Florida
United States	Mayo Clinic - Rochester /ID# 77235	Rochester	Minnesota
United States	University of Arizona Cancer Center - North Campus /ID# 117876	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  France, 

References & Publications (1)

Moreau P, Chanan-Khan A, Roberts AW, Agarwal AB, Facon T, Kumar S, Touzeau C, Punnoose EA, Cordero J, Munasinghe W, Jia J, Salem AH, Freise KJ, Leverson JD, Enschede SH, Ross JA, Maciag PC, Verdugo M, Harrison SJ. Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM. Blood. 2017 Nov 30;130(22):2392-2400. doi: 10.1182/blood-2017-06-788323. Epub 2017 Aug 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of peak concentration (Cmax) of ABT-199	Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints	Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8
Primary	Determine maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of ABT-199	ABT-199 will be dose-escalated until the largest dose is reached that is determined to be safe based on adverse event reporting and dose-limiting toxicities information from all subjects.	Minimum first cycle of dosing (21 days)
Primary	Number of participants with adverse events	Collect all adverse events at each visit.	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.
Primary	Determination of trough concentration (Ctrough) of ABT-199	Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints	Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8
Primary	Determination of area under the concentration versus time curve (AUC) of ABT-199	Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints	Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8
Primary	Determine recommended phase two dose (RPTD) of ABT-199	ABT-199 will be dose-escalated until the largest dose is reached that is determined to be safe based on adverse event reporting and dose-limiting toxicities information from all subjects.	Minimum first cycle of dosing (21 days
Secondary	Duration of Response	Number of days from the day of initial response is objectively documented to the day that disease progression is objectively documented	Measured up to 48 months after the last subject has enrolled in the study
Secondary	Objective Response Rate	The proportion of subjects with response using International Myeloma Working Group (IMWG) response criteria will be computed for all subjects with active disease at baseline (in the opinion of the investigator)	Measured up to 48 months after the last subject has enrolled in the study
Secondary	Time to Disease Progression	Number of days from the date of the first dose of ABT-199 to the date of the subject's disease progression.	Measured up to 48 months after the last subject has enrolled in the study