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

Relapsed or Refractory Hodgkin Lymphoma Clinical Trial

Official title:

An Open-label, Multicenter, Phase 1/2 Study of JNJ-40346527, an FMS Inhibitor, in Subjects With Relapsed or Refractory Hodgkin Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01572519
• Other study ID #: CR100813
• Secondary ID: 40346527HKL10012
• Status: Completed
• Phase: Phase 1
• Start date: July 17, 2012
• Est. completion date: August 13, 2013

Study information

• Verified date: November 2020
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 (although planned, the study did not move forward to the Phase 2 portion). 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: August 13, 2013
• Est. primary completion date: August 13, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma
• Relapsed or Refractory Hodgkin Lymphoma

Intervention

Drug:
• Phase 1, Cohort 1
Type=exact number, unit=mg, number=150, form=capsule, route=oral use. Capsule is taken once daily.
• Phase 1, Cohort 2
Type=exact number, unit=mg, number=300, form=capsule, route=oral use. Capsule is taken once daily.
• Phase 1, Cohort 3
Type=exact number, unit=mg, number=450, form=capsule, route=oral use. Capsule is taken once daily.
• Phase 1, Cohort 4
Type=exact number, unit=mg, number=600, form=capsule, route=oral use. Capsule is taken once daily.
• Phase 2
JNJ-40346527 at the recommended dose determined in Phase 1

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 maximum tolerated dose (MTD) for JNJ-40346527		After completion of Cycle 1 (21 days of dosing) in the last subject in Phase 1
Primary	Phase 2 overall response rate		Up to 6 months after the last subject is enrolled
Secondary	Duration of response (DOR)		Up to 6 months after the last subject is enrolled
Secondary	Progression-free survival (PFS)		Up to 6 months after the last subject is enrolled
Secondary	The number of participants affected by an adverse event		Up to 30 days after the last dose of study medication
Secondary	Maximum observed plasma concentration of JNJ-40346527		Up to treatment cycle Day 21
Secondary	Trough plasma concentration of JNJ-40346527		Up to treatment cycle Day 21
Secondary	Minimum observed plasma concentration of JNJ-40346527		Up to treatment cycle Day 21
Secondary	Time of maximum observed plasma concentration of JNJ-40346527		Up to treatment cycle Day 21
Secondary	Area under the plasma concentration-time curve of JNJ-40346527		Up to treatment cycle Day 21
Secondary	Total drug clearance of JNJ-40346527		Up to treatment cycle Day 21
Secondary	Accumulation index of JNJ-40346527		Up to treatment cycle Day 21

External Links

•   Link to results on EudraCT registry