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Recurrent Mature B-cell NeoplasmsPhase 1NCT01704963

A Study to Evaluate the Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Patients With Recurrent Mature B-Cell Neoplasms

A Phase 1 study testing PCI-32765 in people with Recurrent Mature B-cell Neoplasms, run by Janssen Pharmaceutical K.K. at 4 sites in Japan.

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

The purpose of this study is to evaluate the safety and tolerability of Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Japanese patients with recurrent mature B-cell neoplasms. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Recurrent Mature B-cell Neoplasms
What is being tested?
PCI-32765
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
4 sitesJapan
Study dates
12 Sep 2012to 1 Feb 2017
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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have body weight at least 40 kilogram (kg)
  • Patients with recurrent mature B-cell neoplasms as defined according to WHO classification, including small lymphocytic lymphoma/ chronic lymphocytic leukemia, mantle cell lymphoma, and follicular lymphoma
  • Have measurable disease [for Non-Hodgkin's Lymphoma (NHL) bi-dimensional disease more than or equal to 2 cm diameter in at least one dimension and for chronic lymphocytic leukemia more than or equal to 5000 leukemia cells/cubic mm]
  • Have failed more than or equal to 1 previous treatment and no standard therapy is available
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Who cannot join

  • Patients with plasma cell neoplasm as defined according to WHO classification
  • Patients who have received prior allogeneic hematopoietic stem cell transplant
  • Patients who have received immunotherapy, chemotherapy, radiotherapy or experimental therapy within 4 weeks before first day of study medication
  • Past history of major surgery within 4 weeks before the first day of study medication
  • Patients with central nervous system involvement

Trial locations and contacts

4 sites in 1 country.

Japan4 sites

  • Study site

    Kyoto

  • Study site

    Nagoya

  • Study site

    Sendai

  • Study site

    Tokyo

Other trials in Japan

About this study

Official title: A Phase 1 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Subjects With Recurrent Mature B-Cell Neoplasms

The purpose of this study is to evaluate the safety and tolerability of Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Japanese patients with recurrent mature B-cell neoplasms.

Read the detailed description

This is an open-label (all people know the identity of the intervention), multicenter (study conducted at multiple sites), dose escalation study. The study consists of 3 phases, including, the screening phase (within 14 days prior to the first study medication), the treatment phase, and the follow up phase. In the treatment phase, patients with recurrent mature B-cell neoplasms will be divided into 2 cohorts: Cohort 1 (consisting of between 3 and 12 patients), and Cohort 2 (consisting of between 6 and 12 patients). Cohort 1 will be further divided into 2 phases: a single dose (SD) phase and a multiple dose (MD) phase. During the initial SD phase, patients will first receive a single dose of PCI-32765 at 140 mg. After a washout period (period when the participant is not receiving any study medication) of between 72 and 168 hours, patients will then receive a second single dose of PCI-32765 at 280 mg. Following a second washout period, patients will enter the MD phase, where they will receive PCI-32765 at multiple doses of 420 mg per day for 35 days during the first cycle (35 days in Cycle 1) and for 28 days during the second cycle (28 days in Cycle 2) and every cycle thereafter. In cohort 2, patients will receive multiple doses of 560 mg per day for 35 days in Cycle 1, 28 days in Cycle 2, and every cycle thereafter. The patient's registration in Cohort 2 will be started after tolerability of Cohort 1 is confirmed. Tolerability of each dose level will be evaluated based on the dose-limiting toxicity (DLT) occurrence rate in Cycle 1 of each Cohort. Following the tolerability of the 420 mg/day dose level in subjects with mature B-cell neoplasms is confirmed in Cohort 1, a CLL/SLL Cohort will be added to further evaluate the safety and tolerability of this dose in this specific population in Japanese since 420 mg/day is the globally recommended dose for subjects with CLL and SLL, which are specific disease entities within mature B-cell neoplasms. Between 6 and 12 subjects will be enrolled in the CLL/SLL Cohort and will receive continuous dosing of PCI-32765 at 420 mg/day for 35 days in Cycle 1 and for 28 days in Cycle 2 and thereafter. Safety evaluations for adverse events, clinical laboratory tests, electrocardiogram, vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, physical examination, and corneal eye examination will be monitored throughout the study.

Being tested
PCI-32765
Keywords
Recurrent mature B-cell neoplasms, B-cell malignancies, Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, Tumor, Pharmacokinetics, Japanese
Medical subject headings
Neoplasms

What participants receive

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

  • PCI-32765Drug

    PCI-32765 will be administered in Cohort 1, Cohort 2 and CLL/SLL Cohort. In Cohort 1, single oral dose of PCI-32765 140 mg and 280 mg will be administered before daily oral doses of 420 mg per day for 35 days in Cycle 1 and for 28 days in Cycle 2 and thereafter. In Cohort 2 and CLL/SLL Cohort, PCI-32765 560 mg and 420 mg per day, respectively will be administered daily for 35 days in Cycle 1 and for 28 days in Cycle 2 and thereafter.

Study groups in NCT01704963
Study groupRoleWhat they receive
PCI-32765ExperimentalPatients will receive oral doses of PCI-32765 in Cohort 1, Cohort 2 and CLL/SLL Cohort. In Cohort 1, single oral dose of PCI-32765 140 mg and 280 mg will be given before administration of daily oral doses of 420 mg per day for 35 days in Cycle 1 and for 28 days in Cycle 2 and thereafter. In Cohort 2 and CLL/SLL Cohort, PCI-32765 560 mg and 420 mg per day, respectively will be administered daily for 35 days in Cycle 1 and for 28 days in Cycle 2 and thereafter.
Receives: Drug: PCI-32765

What is being measured

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

  1. Number of patients with adverse events

    Measured: Screening (Day -14) to until 30 days after the last dose

Secondary outcomes (7)

  1. Area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration (AUClast)

    Pharmacokinetic parameter AUClast of PCI-32765 and its metabolite PCI-45227 will be measured when PCI-32765 is administered daily as oral doses in each cohort.

    Measured: Days 1-2, 8-9, 15, 22 and 29 during Cycle 1 of each cohort

  2. Area under the plasma concentration-time curve from time 0 to infinity time (AUC∞)

    Pharmacokinetic parameter AUC∞ of PCI-32765 and its metabolite PCI-45227 will be measured when PCI-32765 is administered daily as oral doses in each cohort.

    Measured: Days 1-2, 8-9, 15, 22 and 29 during Cycle 1 of each cohort

  3. Maximum plasma concentration (Cmax)

    Pharmacokinetic parameter Cmax of PCI-32765 and its metabolite PCI-45227 will be measured when PCI-32765 is administered daily as oral doses in each cohort.

    Measured: Days 1-2, 8-9, 15, 22 and 29 during Cycle 1 of each cohort

  4. Time to reach maximum plasma concentration (tmax)

    Pharmacokinetic parameter tmax of PCI-32765 and its metabolite PCI-45227 will be measured when PCI-32765 is administered daily as oral doses in each cohort.

    Measured: Days 1-2, 8-9, 15, 22 and 29 during Cycle 1 of each cohort

  5. Terminal elimination half-life (t1/2)

    Pharmacokinetic parameter t1/2 of PCI-32765 and its metabolite PCI-45227 will be measured when PCI-32765 is administered daily as oral doses in each cohort.

    Measured: Days 1-2, 8-9, 15, 22 and 29 during Cycle 1 of each cohort

  6. Pharmacodynamic evaluations

    Pharmacodynamic evaluations of PCI-32765 will be conducted under supervision by collecting venous blood samples.

    Measured: Days 1-2, 8-9, 15, and 29 during Cycle 1, and on Days 1 and 15 during Cycle 3, 5, 7, 9, and 11 of each cohort

  7. Tumor response

    Patients will be evaluated for tumor response according to the International Working Group (IWG) Revised Criteria for Malignant Lymphoma or the Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia.

    Measured: Days 22 to 28 of Cycles 2, 4, 6, and every even-numbered cycle thereafter

Timeline

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

  1. First posted12 Oct 2012 (estimated)
  2. Study start12 Sep 2012
  3. Primary completion20 Nov 2015
  4. Study completion1 Feb 2017

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01704963
Sponsor's protocol ID
CR100896
Other IDs
PCI-32765-JPN-101
Status last verified
Jan 2018
First submitted
9 Oct 2012
Last updated
5 Feb 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No

Publications

  • Tobinai K, Ogura M, Ishizawa K, Suzuki T, Munakata W, Uchida T, Aoki T, Morishita T, Ushijima Y, Takahara S. Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies. Int J Hematol. 2016 Jan;103(1):86-94. doi: 10.1007/s12185-015-1900-3. Epub 2015 Nov 20.

    PubMed 26588924

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PCI-32765 in people with Recurrent Mature B-cell Neoplasms, run by Janssen Pharmaceutical K.K. at 4 sites in Japan.

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 5 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Japan. 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?

Number of patients with adverse events (time frame: Screening (Day -14) to until 30 days after the last dose). 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 NCT01704963, 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 5 Feb 2018.

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