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

NCT01794507 | Completed Phase 1 FDA Drug

• 2 other identifiers: M12-9012011-004626-10
• Study Type: interventional
• Target: 66
• Locations: 3 countries
• Sites: 9

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

Keywords

relapsed/refractory multiple myeloma; relapsed multiple myeloma; refractory multiple myeloma; multiple myeloma

Outcome Measures

Primary Outcomes (6)

• 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

• 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)

• 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.

• 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

• 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

• 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 Outcomes (3)

• Duration of Response

  Measured up to 48 months after the last subject has enrolled in the study

• Objective Response Rate

  Measured up to 48 months after the last subject has enrolled in the study

• Time to Disease Progression

  Measured up to 48 months after the last subject has enrolled in the study

Study Arms (2)

ABT-199 + BTZ/Dex Dose Escalation Cohorts

EXPERIMENTAL

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.

Drug: ABT-199; Drug: bortezomib; Drug: dexamethasone

ABT-199 + BTZ/Dex 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.

Drug: ABT-199; Drug: bortezomib; Drug: dexamethasone

Interventions

ABT-199 DRUG

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

ABT-199 + BTZ/Dex Dose Escalation Cohorts; ABT-199 + BTZ/Dex Safety Expansion Cohort

bortezomib DRUG

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

ABT-199 + BTZ/Dex Dose Escalation Cohorts; ABT-199 + BTZ/Dex Safety Expansion Cohort

dexamethasone DRUG

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

ABT-199 + BTZ/Dex Dose Escalation Cohorts; ABT-199 + BTZ/Dex Safety Expansion Cohort

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead
• Genentech, Inc.: collaborator

Study Sites (9)

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

Tucson, Arizona, 85719-1478, United States

Location

Mayo Clinic /ID# 121495

Jacksonville, Florida, 32224, United States

Location

Northwestern University Feinberg School of Medicine /ID# 117477

Chicago, Illinois, 60611-2927, United States

Location

University of Michigan Hospitals /ID# 80353

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic - Rochester /ID# 77235

Rochester, Minnesota, 55905-0001, United States

Location

Peter MacCallum Cancer Ctr /ID# 79553

Melbourne, Victoria, 3000, Australia

Location

Royal Melbourne Hospital /ID# 79533

Parkville, Victoria, 3050, Australia

Location

CHRU Lille - Hôpital Claude Huriez /ID# 77234

Lille, Hauts-de-France, 59045, France

Location

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

Nantes, 44093, France

Location

Related Publications (2)

• 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.

  PMID: 28847998 BACKGROUND

• 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.

  PMID: 26707935 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

venetoclax; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2012
• First Posted: February 20, 2013
• Study Start: November 19, 2012
• Primary Completion: July 16, 2019
• Study Completion: July 16, 2019
• Last Updated: August 2, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); FR (2); US (5)