AzTrials
AzTrials

B-Cell Chronic Lymphocytic LeukemiaPhase 1NCT02381080

Interaction Study of Ibrutinib and Cytochrome P450 (CYP) 3A Inhibitors in Participants With B-cell Malignancy

A Phase 1 study testing Ibrutinib, Erythromycin and Voriconazole in people with B-Cell Chronic Lymphocytic Leukemia, run by Janssen Research & Development, LLC at 6 sites in 3 countries.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to assess the effect of a moderate Cytochrome P450 (CYP) 3A inhibitor (erythromycin) and a strong CYP3A inhibitor (voriconazole) on the steady-state pharmacokinetics (PK [the study of the way a drug enters and leaves the blood and tissues over time]) of repeated oral doses of ibrutinib in… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
B-Cell Chronic Lymphocytic Leukemia
What is being tested?
Ibrutinib, Erythromycin and Voriconazole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
6 sitesin 3 countries
Study dates
19 May 2015to 24 Jun 2016
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone Lymphoma (MZL), Mantle Cell Lymphoma (MCL), Follicular Lymphoma (FL), or Waldenstrom's Macroglobulinemia (WM)
  • Relapsed or refractory disease after at least 1 prior line of systemic therapy (participants with FL or MZL must have failed anti-CD20 monoclonal antibody containing chemotherapy regimen)
  • Eastern Cooperative Oncology Group Performance Status score of 0 or 1
  • Hematology values within the following limits: a) Absolute neutrophil count (ANC) greater than and equal to (>=) 1.0*10^9 per liter (L); b) Platelets >=50*10^9/L without transfusion support within 7 days; c) Hemoglobin >=8 gram per deciliter (g/dL) without transfusion support within 7 days; d) Prothrombin time /International normalized ratio (PT/INR) less than equal to (<=) 1.5*Upper Limit of Normal (ULN) and activated partial thromboplastin time (aPTT) <=1.5*ULN
  • Biochemical values within the following limits: a) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3.0*ULN; b) Total bilirubin <=1.5*ULN (unless due to Gilbert's syndrome); c) Serum creatinine <=1.5*ULN or a calculated creatinine clearance of >=50 milliliter per minute per 1.73 square meter

Who cannot join

  • Major surgery within 4 weeks of the first dose of ibrutinib
  • Diagnosed or treated for malignancy other than the indication under study except for: a) Adequately treated non-melanoma skin cancer or lentigo maligna, curatively treated in-situ cancer without evidence of disease; b) Malignancy treated with curative intent and with no known active disease present for >=3 years before the first dose of ibrutinib
  • History of stroke or intracranial hemorrhage within 6 months prior to the first dose of ibrutinib
  • History of galactose intolerance
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists (for example, phenprocoumon)

Trial locations and contacts

6 sites in 3 countries.

6 sites in 3 countries

Russia3 sites

  • Study site

    Moscow

  • Study site

    Petrozavodsk

  • Study site

    Saint Petersburg

Other trials in Russia

Spain2 sites

  • Study site

    Madrid

  • Study site

    Pamplona

Other trials in Spain

Canada1 site

  • Study site

    N/a N/a

Other trials in Canada

About this study

Official title: A Drug-drug Interaction Study of Ibrutinib With Moderate and Strong CYP3A Inhibitors in Patients With B-cell Malignancy

The purpose of this study is to assess the effect of a moderate Cytochrome P450 (CYP) 3A inhibitor (erythromycin) and a strong CYP3A inhibitor (voriconazole) on the steady-state pharmacokinetics (PK [the study of the way a drug enters and leaves the blood and tissues over time]) of repeated oral doses of ibrutinib in participants with B-cell malignancy (cancer or other progressively enlarging and spreading tumors).

Read the detailed description

This is an open-label (participants and researchers are aware about the treatment participants are receiving), multi-center (when more than 1 hospital or medical school team work on a medical research study), drug-drug interaction (DDI) study of ibrutinib with the moderate and the strong CYP3A inhibitors (erythromycin and voriconazole respectively) in participants with B-cell malignancies (including Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma [CLL/SLL], Follicular Lymphoma [FL], Marginal Zone Lymphoma [MZL], Waldenstrom's Macroglobulinemia [WM] or Mantle Cell Lymphoma [MCL]). The study will consist of a Screening Phase (28 days), a Treatment Phase (consisting of six 28-days cycles), and an End-of-Treatment (EoT) Visit (within 30 days after the last dose of study drug). The study will consist of 2 Parts. In Part 1, extent of the DDI between ibrutinib at dose level of 140 milligram (mg) and CYP3A inhibitors will be assessed. After completion of Part 1 of the study, an interim analysis of all available PK and safety data will be conducted and Part 2 will only be performed if the observed drug interaction is less than anticipated based on current information. In Part 2, safety and PK of ibrutinib at dose level of 560 mg administered with CYP3A inhibitors will be assessed. Participants who continue to derive clinical benefit from ibrutinib treatment at the end of this study, and who are eligible to continue in the PCI-32765CAN3001 study (NCT01804686) will end their participation in this trial, have an EoT visit completed, and will continue receiving ibrutinib as a part of the PCI-32765CAN3001 protocol. Participants' safety will be monitored throughout the study.

Being tested
Ibrutinib, Erythromycin, Voriconazole
Keywords
B-Cell Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Waldenstrom's Macroglobulinemia, Ibrutinib, IMBRUVICA, PCI-32765, JNJ-54179060
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Mantle-Cell, Lymphoma, Follicular, Waldenstrom Macroglobulinemia

What participants receive

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

  • IbrutinibDrug

    Also called Imbruvica, PCI-32765, JNJ-54179060

    Ibrutinib capsule (at dose level of 140 or 420 or 560 mg) will be taken orally QD up to six, 28-days cycles.

  • ErythromycinDrug

    Also called Erythrocin

    Erythromycin 500 mg tablet will be taken orally TID (Part1 Cycle 1: on Days 5-10 and morning dose on Day 11; Part2 Cycle 1: on Days 5-17 and morning dose on Day 18).

  • VoriconazoleDrug

    Also called VFEND

    Voriconazole 200 mg tablet will be taken orally BD (Part1 Cycle 1: on Days 19-25; Part2 Cycle 1: on Days 5-17).

Study groups in NCT02381080
Study groupRoleWhat they receive
Part 1: Ibrutinib+Erythromycin+VoriconazoleExperimentalParticipants will receive oral treatment in six, 28-days cycles. In Cycle 1, participants will take ibrutinib 560 milligram (mg) (4*140 mg capsules) once daily (QD) from Days 1- 4; on Days 5-11 ibrutinib 140 mg capsule QD in combination with erythromycin 500 mg tablet 3 times daily (TID); on Days 12-13 ibrutinib 140 mg capsule QD; on Days 14-18 ibrutinib 560 mg (4*140 mg capsules) QD; on Days 19-25 ibrutinib 140 mg capsule QD in combination with voriconazole 200 mg tablet twice daily (BD); on Days 26-27 ibrutinib 140 mg capsule orally QD; and on Day 28 and in subsequent treatment Cycles (2-6) participants will continue oral treatment with ibrutinib 420 mg or 560 mg QD (depending on the subtype of B-cell malignancy).
Receives: Drug: Ibrutinib; Drug: Erythromycin; Drug: Voriconazole
Part 2: Ibrutinib+ Erythromycin+VoriconazoleExperimentalParticipants will receive oral treatment in six, 28-days cycles. In Cycle 1, participants will take ibrutinib 560 mg (4*140 mg capsules) QD from Days 1- 4; on Days 5-18 ibrutinib 560 mg (4*140 mg capsules) QD in combination with either erythromycin 500 mg tablet TID (Group 1) or voriconazole 200 mg tablet BD (Group 2); on Day 19 and in subsequent treatment Cycles (2-6) participants will continue oral treatment with ibrutinib 420 mg or 560 mg QD (depending on the subtype of B-cell malignancy).
Receives: Drug: Ibrutinib; Drug: Erythromycin; Drug: Voriconazole

What is being measured

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

  1. Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

    The Cmax is the maximum observed plasma concentration.

    Measured: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25

  2. Minimum Observed Plasma Concentration (Cmin) of Ibrutinib

    The Cmin is the minimum observed plasma concentration.

    Measured: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25

  3. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib

    The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

    Measured: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25

  4. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Ibrutinib

    The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.

    Measured: Cycle 1: 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25

  5. Metabolite to Parent (M/P) Ratio of Ibrutinib

    Ratio of ibrutinib metabolite concentration to parent compound (ibrutinib) concentration will be assessed.

    Measured: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25

Secondary outcomes (2)

  1. Partial Area Under the Plasma Concentration-Time Curve Between 2 Defined Timepoints (AUC [t1 and t2]) of Voriconazole

    The AUC (t1 and t2) is the partial area under the plasma concentration-time curve from time 't1' to 't2' hours.

    Measured: Cycle 1: 0 hour (hr) pre-dose on Day 5; 0 hr pre-dose, 0.5,1,2,3,4,6 and 24 hrs post-dose on Day 18 and 25

  2. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.

    Measured: Screening up to end of study (up to 8 months)

Timeline

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

  1. First posted6 Mar 2015 (estimated)
  2. Study start19 May 2015
  3. Primary completion24 Jun 2016
  4. Study completion24 Jun 2016

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
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02381080
Sponsor's protocol ID
CR106609
Other IDs
PCI-32765LYM1003, 2015-000325-36, 2015
Status last verified
Jun 2017
First submitted
2 Mar 2015
Last updated
26 Jun 2017
Results posted
No
Data monitoring committee
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ibrutinib, Erythromycin and Voriconazole in people with B-Cell Chronic Lymphocytic Leukemia, run by Janssen Research & Development, LLC at 6 sites in 3 countries.

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 5 inclusion and 5 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 26 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Russia, Spain, Canada. 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?

Maximum Observed Plasma Concentration (Cmax) of Ibrutinib (time frame: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25). The study lists 5 primary outcomes in all. 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 NCT02381080.

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 26 Jun 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in