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

NCT ID: NCT01794507

Last Updated: 2021-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-19
• Study Completion Date: 2019-07-16

Brief 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.

Conditions

Relapsed/Refractory Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ABT-199 + BTZ/Dex Dose Escalation Cohorts

Evaluate the safety and pharmacokinetics profile of ABT-199 administered with standard therapy bortezomib and dexamethasone in a dose escalation scheme in approximately 54 subjects.

Group Type: EXPERIMENTAL

ABT-199

Intervention Type: DRUG

ABT-199 at cohort-defined dosing schedules and dose levels. ABT-199 at defined dose and schedule for Safety Expansion cohort

bortezomib

Intervention Type: DRUG

Bortezomib at cohort-defined dosing schedules and dose levels. Bortezomib at defined dose and schedule for Safety Expansion cohort

dexamethasone

Intervention Type: DRUG

Dexamethasone at cohort-defined dosing schedules and dose levels. Dexamethasone at defined dose and schedule for Safety Expansion cohort.

ABT-199 + BTZ/Dex Safety Expansion Cohort

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.

Group Type: EXPERIMENTAL

ABT-199

Intervention Type: DRUG

ABT-199 at cohort-defined dosing schedules and dose levels. ABT-199 at defined dose and schedule for Safety Expansion cohort

bortezomib

Intervention Type: DRUG

Bortezomib at cohort-defined dosing schedules and dose levels. Bortezomib at defined dose and schedule for Safety Expansion cohort

dexamethasone

Intervention Type: DRUG

Dexamethasone at cohort-defined dosing schedules and dose levels. Dexamethasone at defined dose and schedule for Safety Expansion cohort.

Interventions

ABT-199

ABT-199 at cohort-defined dosing schedules and dose levels. ABT-199 at defined dose and schedule for Safety Expansion cohort

Intervention Type: DRUG

bortezomib

Bortezomib at cohort-defined dosing schedules and dose levels. Bortezomib at defined dose and schedule for Safety Expansion cohort

Intervention Type: DRUG

dexamethasone

Dexamethasone at cohort-defined dosing schedules and dose levels. Dexamethasone at defined dose and schedule for Safety Expansion cohort.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

University of Arizona Cancer Center - North Campus /ID# 117876

Tucson, Arizona, United States

Mayo Clinic /ID# 121495

Jacksonville, Florida, United States

Northwestern University Feinberg School of Medicine /ID# 117477

Chicago, Illinois, United States

University of Michigan Hospitals /ID# 80353

Ann Arbor, Michigan, United States

Mayo Clinic - Rochester /ID# 77235

Rochester, Minnesota, United States

Peter MacCallum Cancer Ctr /ID# 79553

Melbourne, Victoria, Australia

Royal Melbourne Hospital /ID# 79533

Parkville, Victoria, Australia

CHRU Lille - Hôpital Claude Huriez /ID# 77234

Lille, Hauts-de-France, France

CHU de Nantes, Hotel Dieu -HME /ID# 78773

Nantes, , France

Countries

United States; Australia; France

References

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.

Reference Type: BACKGROUND

PMID: 28847998 (View on PubMed)

Matulis SM, Gupta VA, Nooka AK, Hollen HV, Kaufman JL, Lonial S, Boise LH. Dexamethasone treatment promotes Bcl-2 dependence in multiple myeloma resulting in sensitivity to venetoclax. Leukemia. 2016 May;30(5):1086-93. doi: 10.1038/leu.2015.350. Epub 2015 Dec 28.

Reference Type: DERIVED

PMID: 26707935 (View on PubMed)

Other Identifiers

2011-004626-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M12-901

Identifier Type: -

Identifier Source: org_study_id