Clinical trial NCT01794507: A Study Evaluating ABT-199 in Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Standard Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed/Refractory Multiple Myeloma
Keywords: relapsed/refractory multiple myeloma
relapsed multiple myeloma
refractory multiple myeloma
multiple myeloma
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2013-02-20
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Determination of peak concentration (Cmax) of ABT-199
timeFrame: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8
measure: Determine maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of ABT-199
timeFrame: Minimum first cycle of dosing (21 days)
measure: Number of participants with adverse events
timeFrame: 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.
measure: Determination of trough concentration (Ctrough) of ABT-199
timeFrame: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8
measure: Determination of area under the concentration versus time curve (AUC) of ABT-199
timeFrame: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8
measure: Determine recommended phase two dose (RPTD) of ABT-199
timeFrame: Minimum first cycle of dosing (21 days
Secondary outcomes:
measure: Duration of Response
timeFrame: Measured up to 48 months after the last subject has enrolled in the study
measure: Objective Response Rate
timeFrame: Measured up to 48 months after the last subject has enrolled in the study
measure: Time to Disease Progression
timeFrame: Measured up to 48 months after the last subject has enrolled in the study
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center - North Campus /ID# 117876
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic /ID# 121495
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine /ID# 117477
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan Hospitals /ID# 80353
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester /ID# 77235
state: Minnesota
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Ctr /ID# 79553
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital /ID# 79533
state: Victoria
city: Lille CEDEX
country: France
facility: CHRU Lille - Hôpital Claude Huriez /ID# 77234
state: Hauts-de-France
city: Nantes
country: France
facility: CHU de Nantes, Hotel Dieu -HME /ID# 78773
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.