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

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

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.

Study Overview

• Status: Completed
• Conditions: Relapsed or Refractory Hodgkin Lymphoma
• Intervention / Treatment: Drug: Phase 1, Cohort 1; Drug: Phase 1, Cohort 2; Drug: Phase 1, Cohort 3; Drug: Phase 1, Cohort 4; Drug: Phase 2

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 (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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Lille, France
  • Villejuif, France
• Germany
  • Köln, Germany
  • Würzburg, Germany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
Phase 2 overall response rate	Up to 6 months after the last subject is enrolled

Secondary Outcome Measures

Outcome Measure	Time Frame
The number of participants affected by an adverse event	Up to 30 days after the last dose of study medication
Duration of response (DOR)	Up to 6 months after the last subject is enrolled
Progression-free survival (PFS)	Up to 6 months after the last subject is enrolled
Maximum observed plasma concentration of JNJ-40346527	Up to treatment cycle Day 21
Trough plasma concentration of JNJ-40346527	Up to treatment cycle Day 21
Minimum observed plasma concentration of JNJ-40346527	Up to treatment cycle Day 21
Time of maximum observed plasma concentration of JNJ-40346527	Up to treatment cycle Day 21
Area under the plasma concentration-time curve of JNJ-40346527	Up to treatment cycle Day 21
Total drug clearance of JNJ-40346527	Up to treatment cycle Day 21
Accumulation index of JNJ-40346527	Up to treatment cycle Day 21

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

Helpful Links

• Link to results on EudraCT registry

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2012
• Primary Completion (Actual): August 13, 2013
• Study Completion (Actual): August 13, 2013

Study Registration Dates

• First Submitted: February 16, 2012
• First Submitted That Met QC Criteria: April 4, 2012
• First Posted (Estimate): April 6, 2012

Study Record Updates

• Last Update Posted (Actual): November 20, 2020
• Last Update Submitted That Met QC Criteria: November 18, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Dose-escalation; Relapsed Hodgkin lymphoma; Refractory Hodgkin lymphoma; JNJ-40346527
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease
• Other Study ID Numbers: CR100813; 40346527HKL1001 (Other Identifier: Janssen Research & Development, LLC); 2011-005795-42 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No