NCT01969669

Brief Summary

This is an open-label multicenter, study to assess the pharmacokinetic interaction of ketoconazole with ABT-199 in up to 12 subjects with relapsed or refractory non-Hodgkin's lymphoma.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Dec 2013

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 22, 2013

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 25, 2013

Completed
1 month until next milestone

Study Start

First participant enrolled

December 1, 2013

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2014

Completed
Last Updated

November 20, 2017

Status Verified

October 1, 2014

Enrollment Period

9 months

First QC Date

October 22, 2013

Last Update Submit

November 16, 2017

Conditions

Non-Hodgkin's Lymphoma

Keywords

non-Hodgkin's lymphomaGDC-0199SafetyRelapsedRefractoryABT-199PharmacokineticsCancer

Outcome Measures

Primary Outcomes (1)

  • Determination of maximum observed plasma concentration (Cmax), time to Cmax (peak time, Tmax), terminal phase elimination rate constant (beta), terminal phase elimination half-life (t1/2), & area under the plasma concentration-time curve (AUC) of ABT-199

    Blood samples for pharmacokinetic (PK) analysis of ABT-199 will be collected at designated timepoints to assess the PK parameters for ABT-199 alone relative to ABT-199 with ketoconazole

    Measured pre-dose and up to 96 hours post-dose ABT-199

Secondary Outcomes (5)

  • Number of subjects with adverse events

    Measured up to 30 days after the last dose of study drug

  • Percentage of subjects with adverse events

    Measured up to 30 days after the last dose of study drug

  • Change in physical exam finding, including vital signs

    Measured from Day 1 up to 30 days after the last dose of study drug

  • Change in clinical laboratory test results

    Measured from Day 1 up to 30 days after the last dose of study drug

  • Change in cardiac assessment findings

    Measured from Day 1 up to Day 12

Study Arms (1)

Arm A (ABT-199 and ketoconazole)

EXPERIMENTAL
Drug: ABT-199Drug: Ketoconazole

Interventions

ABT-199DRUG

Subjects will be dosed with ABT-199, then dosed with ABT-199 in combination with ketoconazole

Also known as: GDC-0199
Arm A (ABT-199 and ketoconazole)
KetoconazoleDRUG

Subjects will be dosed with ABT-199, then dosed with ABT-199 in combination with ketoconazole

Arm A (ABT-199 and ketoconazole)

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subject must have relapsed or refractory non-Hodgkin's lymphoma.

You may not qualify if:

  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.
  • Subject must have adequate bone marrow (independent of growth factor support per local laboratory reference range), coagulation, renal and hepatic function:
  • Absolute Neutrophil Count (ANC) greater than or equal to 1000/µL (without growth factor support unless neutropenia is clearly due to underlying disease);
  • Platelets greater than or equal to 75,000/mm3 (unless thrombocytopenia is clearly due to disease-related immune thrombocytopenia or to underlying disease; entry platelet count must be independent of transfusion within 14 days of Screening);
  • Hemoglobin greater than or equal to 9.0 g/dL (unless anemia is clearly due to underlying disease; entry hemoglobin must be independent of transfusion within 14 days of Screening);
  • If cytopenias are present, no evidence of myelodysplastic syndrome or hypoplastic bone marrow;
  • Subject must have activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5 × the upper normal limit (ULN);
  • Calculated creatinine clearance greater than or equal to 50 mL/min using a 24-hour urine collection for creatinine clearance or per the Cockcroft-Gault equation;
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3.0 × ULN of institution's normal range;
  • Bilirubin less than or equal to 1.5 × ULN. Subjects with Gilbert's Syndrome may have a bilirubin greater than 1.5 × ULN per discussion with the AbbVie medical monitor.
  • Subject has been diagnosed with Post-Transplant Lymphoproliferative Disease (PTLD), Burkitt's lymphoma, Burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or mantle cell lymphoma (MCL).
  • Subject is receiving combination anti-retroviral therapy for HIV (due to potential drug-drug interactions between anti-retroviral medications and ABT-199, as well as anticipated ABT-199 mechanism based lymphopenia that may potentially increase the risk of opportunistic infections).
  • Subject has hypersensitivity to ketoconazole.
  • Subject has a 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.
  • Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease within the past 6 months that in the opinion of the investigator would adversely affect his/her participating in this study.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Site Reference ID/Investigator# 97498

Tucson, Arizona, 85724-5024, United States

Location

Site Reference ID/Investigator# 92593

Lebanon, New Hampshire, 03756-0001, United States

Location

Site Reference ID/Investigator# 101415

Hackensack, New Jersey, 07601, United States

Location

Related Publications (1)

  • Agarwal SK, Salem AH, Danilov AV, Hu B, Puvvada S, Gutierrez M, Chien D, Lewis LD, Wong SL. Effect of ketoconazole, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax, a BCL-2 inhibitor, in patients with non-Hodgkin lymphoma. Br J Clin Pharmacol. 2017 Apr;83(4):846-854. doi: 10.1111/bcp.13175. Epub 2017 Jan 18.

    PMID: 27859472RESULT

MeSH Terms

Conditions

Lymphoma, Non-HodgkinRecurrenceNeoplasms

Interventions

venetoclaxKetoconazole

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PiperazinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • David Chien, MD

    AbbVie

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 22, 2013

First Posted

October 25, 2013

Study Start

December 1, 2013

Primary Completion

September 1, 2014

Study Completion

September 1, 2014

Last Updated

November 20, 2017

Record last verified: 2014-10

Locations

US(3)