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

• 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 ]
  

• 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 ]
  

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.