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

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ClinicalTrials.gov Identifier: NCT01704963
Recruitment Status : Completed
First Posted : October 12, 2012
Last Update Posted : February 2, 2018
Sponsor:
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.

Brief 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.

Condition or disease Intervention/treatment Phase
Recurrent Mature B-cell Neoplasms Drug: PCI-32765 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Subjects With Recurrent Mature B-Cell Neoplasms
Actual Study Start Date : September 12, 2012
Actual Primary Completion Date : November 20, 2015
Actual Study Completion Date : February 1, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Ibrutinib

Arm Intervention/treatment
Experimental: PCI-32765
Patients 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.
Drug: PCI-32765
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.




Primary Outcome Measures :
  1. Number of patients with adverse events [ Time Frame: Screening (Day -14) to until 30 days after the last dose ]

Secondary Outcome Measures :
  1. Area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration (AUClast) [ Time Frame: Days 1-2, 8-9, 15, 22 and 29 during Cycle 1 of each cohort ]
    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.

  2. Area under the plasma concentration-time curve from time 0 to infinity time (AUC∞) [ Time Frame: Days 1-2, 8-9, 15, 22 and 29 during Cycle 1 of each cohort ]
    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.

  3. Maximum plasma concentration (Cmax) [ Time Frame: Days 1-2, 8-9, 15, 22 and 29 during Cycle 1 of each cohort ]
    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.

  4. Time to reach maximum plasma concentration (tmax) [ Time Frame: Days 1-2, 8-9, 15, 22 and 29 during Cycle 1 of each cohort ]
    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.

  5. Terminal elimination half-life (t1/2) [ Time Frame: Days 1-2, 8-9, 15, 22 and 29 during Cycle 1 of each cohort ]
    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.

  6. Pharmacodynamic evaluations [ Time Frame: 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 ]
    Pharmacodynamic evaluations of PCI-32765 will be conducted under supervision by collecting venous blood samples.

  7. Tumor response [ Time Frame: Days 22 to 28 of Cycles 2, 4, 6, and every even-numbered cycle thereafter ]
    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.



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01704963


Locations
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Japan
Kyoto, Japan
Nagoya, Japan
Sendai, Japan
Tokyo, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Pharmacyclics LLC.
Investigators
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Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial Janssen Pharmaceutical K.K.

Additional Information:
Publications of Results:
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Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT01704963     History of Changes
Other Study ID Numbers: CR100896
PCI-32765-JPN-101 ( Other Identifier: Janssen Pharmaceutical K.K., Japan )
First Posted: October 12, 2012    Key Record Dates
Last Update Posted: February 2, 2018
Last Verified: January 2018

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Studies a U.S. FDA-regulated Drug Product: No
Keywords provided by Janssen Pharmaceutical K.K.:
Recurrent mature B-cell neoplasms
B-cell malignancies
Bruton's Tyrosine Kinase (Btk) Inhibitor
PCI-32765
Tumor
Pharmacokinetics
Japanese
Additional relevant MeSH terms:
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Lymphoma, B-Cell
Neoplasms
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases