Purpose

The phase 1 primary objectives of this study are to assess the safety profile, characterize pharmacokinetics (PK) and determine the dosing schedule, maximum tolerated dose (MTD), and recommended phase 2 dose (RPTD) of ABT-199 (venetoclax) when administered in subjects with relapsed or refractory multiple myeloma. This study will also assess the safety profile and PK of venetoclax in combination with dexamethasone in subjects with t(11;14)-positive multiple myeloma. The phase 2 primary objective is to further evaluate the objective response rate (ORR) and very good partial response or better rate (VGPR+) in subjects with t(11;14)-positive multiple myeloma.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • ECOG (Eastern Cooperative Oncology Group) performance score of 1 or 0. Subjects in the Phase 2 portion: ECOG performance score of 2, 1, or 0.
  • Diagnosis of multiple myeloma previously treated with at least one prior line of therapy. Induction therapy followed by stem cell transplant and maintenance therapy will be considered a single line of therapy. For Safety Expansion, subjects must have been previously treated with a proteasome inhibitor (e.g., bortezomib) and an immunomodulatory agent (e.g., thalidomide, lenalidomide). For Venetoclax-Dexamethasone Combination, subjects must have been been previously treated with a proteasome inhibitor (e.g., bortezomib) and an immunomodulatory agent (e.g., thalidomide, lenalidomide) AND have t(11;14)-positive multiple myeloma per the central lab testing. For Phase 2, subjects must have MM positive for the t(11;14) translocation, as determined by an analytically validated fluorescence in situ hybridization (FISH) assay per the central laboratory testing (enrollment with local t(11;14)-positive FISH results only will be considered at the discretion of the TA MD) Subjects must have evidence of disease progression on or within 60 days of last dose of most recent previous treatment based on IMWG criteria AND Subject must have previously received at least 2 lines of therapy, including an immunomodulatory drug (lenalidomide or pomalidomide), a proteasome inhibitor (bortezomib, carfilzomib or ixazomib), daratumumab, and glucocorticoids.
  • For US subjects: Daratumumab combination regimen must be one of the prior lines of therapy (for this study, daratumumab plus corticosteroids will not be considered a combination regimen)
  • For Non-US Subjects: Either daratumumab monotherapy or combination therapy is acceptable. Daratumumab monotherapy will be limited to approximately 20 percent of the total number of Phase 2 subjects.
  • Measurable disease at Screening: Serum monoclonal protein of at least 1.0 g/dL (10g/L) by protein electrophoresis or at least 200 mg of monoclonal protein in the urine on 24-hr electrophoresis or serum immunoglobulin free light chain of at least 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio.
  • Subjects with a history of autologous or allogenic stem cell transplantation must have adequate peripheral blood counts independent of any growth factor support, and have recovered from any transplant related toxicity(s) and be at least 100 days post-autologous transplant prior to first dose of study drug or at least 6 months post-allogenic transplant prior to first dose of study drug and not have active graft-versus-host disease (GVHD), i.e., requiring treatment.
  • Meet the following laboratory parameters, per the reference range, at least once during the screening period: ANC of at least 1000/μL (Subjects may use growth factor support to achieve ANC eligibility criteria), AST and ALT not higher than 3 x ULN, Calculated creatinine clearance of at least 30 mL/min using a modified Cockcroft-Gault calculation, platelet count of at least 30,000 mm³ (independent of transfusion for 2 weeks), hemoglobin of at least 8.0 g/dL (subjects may receive blood transfusion to achieve hemoglobin eligibility criteria), and total bilirubin not higher than 1.5 x ULN (subjects with Gilbert's Syndrome may have bilirubin higher 1.5 x ULN).

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 3.
  • Significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular or hepatic disease, within the last 6 months 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, localized prostate cancer Gleason grade 6 or lower AND with stable prostate specific antigen (PSA) levels off treatment, previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  • Known HIV infection.
  • Active hepatitis B or C infection

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
ABT-199 Safety Expansion Cohort
  • Drug: ABT-199
    ABT-199 dosed at cohort-defined dosing schedules
Experimental
Phase 2 Cohort
Venetoclax-Dexamethasone Combination Expansion
  • Drug: ABT-199
    ABT-199 dosed at cohort-defined dosing schedules
Experimental
Venetoclax-Dexamethasone Combination
  • Drug: Dexamethasone
    Dexamethasone at defined dose and schedule for Venetoclax-Dexamethasone combination cohort.
  • Drug: ABT-199
    ABT-199 dosed at cohort-defined dosing schedules
Experimental
ABT-199 Dose Escalation Cohorts
  • Drug: ABT-199
    ABT-199 dosed at cohort-defined dosing schedules

Recruiting Locations

Mayo Clinic - Scottsdale /ID# 75808
Scottsdale, Arizona 85259

University of Arkansas for Medical Sciences /ID# 170002
Little Rock, Arkansas 72205

Emory University Hospital /ID# 74993
Atlanta, Georgia 30322

Ingalls Memorial Hosp /ID# 205346
Harvey, Illinois 60426

Mayo Clinic - Rochester /ID# 74994
Rochester, Minnesota 55905-0001

Washington University-School of Medicine /ID# 76094
Saint Louis, Missouri 63110

Duke Univ Med Ctr /ID# 129356
Durham, North Carolina 27710

Avera Cancer Institute /ID# 204178
Sioux Falls, South Dakota 57105

Univ of Wisconsin Hosp/Clinics /ID# 200246
Madison, Wisconsin 53792-0001

More Details

NCT ID
NCT01794520
Status
Recruiting
Sponsor
AbbVie

Study Contact

ABBVIE CALL CENTER
847.283.8955
abbvieclinicaltrials@abbvie.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.