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Non-Hodgkin's LymphomaPhase 1NCT01969669

A Study to Assess the Effect of Ketoconazole on the Metabolism of ABT-199

A Phase 1 study testing ABT-199 and Ketoconazole in people with Non-Hodgkin's Lymphoma, run by AbbVie at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Non-Hodgkin's Lymphoma
What is being tested?
ABT-199 and Ketoconazole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
3 sitesUnited States
Study dates
Dec 2013to Sep 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject must have relapsed or refractory non-Hodgkin's lymphoma.
  • Subject must have histologically documented diagnosis of non-Hodgkin's lymphoma as defined by a B-cell neoplasm in the World Health Organization (WHO) classification scheme except as noted in the exclusion criteria.
  • 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);
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  • 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.

Who cannot join

  • 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.
  • Subject has malabsorption syndrome or other condition which precludes enteral route of administration (e.g., prior surgical resection).
  • Subject has undergone an allogeneic stem cell transplant.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Site Reference ID/Investigator# 101415

    Hackensack, New Jersey, 07601

  • Site Reference ID/Investigator# 92593

    Lebanon, New Hampshire, 03756-0001

  • Site Reference ID/Investigator# 97498

    Tucson, Arizona, 85724-5024

Other trials in United States

About this study

Official title: A Phase 1 Study to Assess the Effect of Ketoconazole on the Pharmacokinetics of ABT-199

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.

Read the detailed description

This is a Phase 1 study designed to assess how the body processes the study drug ABT-199 when taken alone and in combination with ketoconazole and to assess the safety of ABT-199 in combination with ketoconazole. Subjects may enroll in a separate extension study to continue receiving ABT-199 after completion of this study.

Being tested
ABT-199, Ketoconazole
Keywords
non-Hodgkin's lymphoma, GDC-0199, Safety, Relapsed, Refractory, ABT-199, Pharmacokinetics, Cancer
Medical subject headings
Lymphoma, Non-Hodgkin, Recurrence, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ABT-199Drug

    Also called GDC-0199

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

  • KetoconazoleDrug

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

Study groups in NCT01969669
Study groupRoleWhat they receive
Arm A (ABT-199 and ketoconazole)ExperimentalNot described
Receives: Drug: ABT-199; Drug: Ketoconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (5)

  1. Number of subjects with adverse events

    Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study

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

  2. Percentage of subjects with adverse events

    Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study

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

  3. Change in physical exam finding, including vital signs

    Body temperature, weight, blood pressure, heart rate

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

  4. Change in clinical laboratory test results

    Chemistry, coagulation, hematology, urinalysis

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

  5. Change in cardiac assessment findings

    Electrocardiogram

    Measured: Measured from Day 1 up to Day 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2013 (estimated)
  2. Study startDec 2013
  3. Primary completionSep 2014
  4. Study completionSep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01969669
Sponsor's protocol ID
M13-364
Status last verified
Oct 2014
First submitted
22 Oct 2013
Last updated
20 Nov 2017
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 27859472

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ABT-199 and Ketoconazole in people with Non-Hodgkin's Lymphoma, run by AbbVie at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Measured pre-dose and up to 96 hours post-dose ABT-199). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01969669, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2017.

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