A Study of JNJ-40346527 in Patients With Relapsed or Refractory Hodgkin Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01572519
First received: February 16, 2012
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to determine the safety, pharmacokinetics, and preliminary efficacy information of JNJ-40346527 in patients with relapsed or refractory Hodgkin lymphoma.


Condition Intervention Phase
Relapsed or Refractory Hodgkin Lymphoma
Drug: Phase 1, Cohort 1
Drug: Phase 1, Cohort 2
Drug: Phase 1, Cohort 3
Drug: Phase 1, Cohort 4
Drug: Phase 2
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter, Phase 1/2 Study of JNJ-40346527, an FMS Inhibitor, in Subjects With Relapsed or Refractory Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Phase 1 maximum tolerated dose (MTD) for JNJ-40346527 [ Time Frame: After completion of Cycle 1 (21 days of dosing) in the last subject in Phase 1 ] [ Designated as safety issue: Yes ]
  • Phase 2 overall response rate [ Time Frame: Up to 6 months after the last subject is enrolled ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of response (DOR) [ Time Frame: Up to 6 months after the last subject is enrolled ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: Up to 6 months after the last subject is enrolled ] [ Designated as safety issue: No ]
  • The number of participants affected by an adverse event [ Time Frame: Up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
  • Maximum observed plasma concentration of JNJ-40346527 [ Time Frame: Up to treatment cycle Day 21 ] [ Designated as safety issue: No ]
  • Trough plasma concentration of JNJ-40346527 [ Time Frame: Up to treatment cycle Day 21 ] [ Designated as safety issue: No ]
  • Minimum observed plasma concentration of JNJ-40346527 [ Time Frame: Up to treatment cycle Day 21 ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration of JNJ-40346527 [ Time Frame: Up to treatment cycle Day 21 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve of JNJ-40346527 [ Time Frame: Up to treatment cycle Day 21 ] [ Designated as safety issue: No ]
  • Total drug clearance of JNJ-40346527 [ Time Frame: Up to treatment cycle Day 21 ] [ Designated as safety issue: No ]
  • Accumulation index of JNJ-40346527 [ Time Frame: Up to treatment cycle Day 21 ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: June 2012
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: JNJ-40346527 Drug: Phase 1, Cohort 1
Type=exact number, unit=mg, number=150, form=capsule, route=oral use. Capsule is taken once daily.
Drug: Phase 1, Cohort 2
Type=exact number, unit=mg, number=300, form=capsule, route=oral use. Capsule is taken once daily.
Drug: Phase 1, Cohort 3
Type=exact number, unit=mg, number=450, form=capsule, route=oral use. Capsule is taken once daily.
Drug: Phase 1, Cohort 4
Type=exact number, unit=mg, number=600, form=capsule, route=oral use. Capsule is taken once daily.
Drug: Phase 2
JNJ-40346527 at the recommended dose determined in Phase 1

Detailed Description:

This is an open-label (individuals will know the identity of study treatments), dose-escalation study to evaluate the clinical efficacy, safety, and pharmacokinetics (PK; study of what the body does to a drug) of JNJ-40346527. Up to 38 subjects could be enrolled in the Phase 1 portion of the study and up to 30 subjects could be enrolled in the Phase 2 portion of the study. During the Phase 1 portion of the study, dose escalation of JNJ-40346527 will start at 150 mg (Cohort 1) once daily up to the maximum tolerated dose (MTD) or the highest planned dose (600 mg once daily); twice daily dosing may also be performed if deemed necessary. A Study Evaluation Team (SET) will review all available data after 1 cycle (21 days) of treatment for each cohort before any additional dose escalation occurs and will also determine the recommended Phase 2 dose for the expansion cohort. This study will consist of 3 periods: a screening period (from signing of informed consent until immediately before dosing), an open-label treatment period (from the first dose of study drug until the end-of-treatment visit), and a follow-up period (after the end-of-treatment visit). All patients will participate in the screening and treatment period. Patients will be administered JNJ-40346527 continuously until disease progression, or unacceptable toxicity (based on investigator assessment). The National Cancer Institute-Common Terminology Criteria for Adverse Events will be used to grade toxicity throughout the study. Disease response will be assessed according to the Revised Response Criteria for Malignant Lymphoma. Treatment will continue until disease progression or unacceptable toxicity (based on investigator assessment) occurs. Only patients who discontinue study drug before disease progression or discontinue due to treatment-related Grade 3 or higher toxicity will continue in the follow-up period. Serial PK samples will be collected in Cycle 1 as detailed in the protocol. Safety will be monitored throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Patients with histopathologically confirmed initial diagnosis of Hodgkin lymphoma and who have disease that has relapsed or is refractory that is progressing or active and requires treatment after at least 1 appropriate therapy

Exclusion Criteria:

  • Known brain metastases or leptomeningeal disease
  • Other malignancy within past 5 years
  • Has any condition that, in the opinion of the investigator, would make study participation not be in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments
  • QTc prolongation at screening or other factors that increase the risk of QT prolongation such as diagnosis or family history of long-QT syndrome, diagnosed or suspected congenital long QT syndrome, or concomitant use of medication that can prolong the QT interval
  • Taking CYP3A4 substrate drugs with a narrow therapeutic index (eg, alfentanil, astemizole, sirolimus, tacrolimus, terfenadine)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01572519

Locations
France
Lille, France
Villejuif, France
Germany
Köln, Germany
Würzburg, Germany
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01572519     History of Changes
Other Study ID Numbers: CR100813, 40346527HKL1001, 2011-005795-42
Study First Received: February 16, 2012
Last Updated: June 6, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ethics Commission
United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Relapsed Hodgkin lymphoma
Refractory Hodgkin lymphoma
JNJ-40346527
Dose-escalation
Pharmacokinetics

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 01, 2014