Clinical Trial: Study to Evaluate Activity of 2 Dose Levels of Imetelstat in Participants With Intermediate-2 or High-Risk Myelofibrosis (MF) Previously Treated With Janus Kinase (JAK) Inhibitor

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: A Randomized, Single-Blind, Multicenter Phase 2 Study to Evaluate the Activity of 2 Dose Levels of Imetelstat in Subjects With Intermediate-2 or High-Risk Myelofibrosis (M

Brief Summary: The purpose of this study is to evaluate the percentage of spleen (largest lymph organ in the body) response and symptom response of 2 dose regimens of imetelstat in participants with intermediate-2 or high-risk myelofibrosis (MF) who are relapsed after or refractory to Janus Kinase (JAK) inhibitor treatment.

Detailed Summary: This is a randomized (study medication assigned to participants by chance), multicenter (more than one hospital, medical school team or medical clinic work on a medical research study) study of 2 dosing regimens (treatment arms) of single-agent imetelstat in participants with intermediate-2 or high risk myelofibrosis (MF) whose disease is relapsed after or refractory to Janus Kinase (JAK) inhibitor treatment. Enrollment in the study may be approximately 160 participants if enrollment in Arm 1 is resumed after the second interim review. The study consists of 3 parts: Screening Phase (21 days before randomization); single-blind Treatment Phase (from randomization until study drug discontinuation); and Follow up Phase (until death, lost to follow-up, withdrawal of consent or study end, whichever occurs first). Participants in Arm 1 will receive imetelstat 9.4 milligram (mg)/kilogram (kg) intravenously (IV) for every 3 weeks until disease progression, unacceptable toxicity, or study end and Arm 2 will receive imetelstat 4.7 mg/kg IV for every 3 weeks until disease progression, unacceptable toxicity, or study end. Participants in Arm 2 may continue with their current imetelstat dose or have it increased to 9.4 mg/kg at the investigator's discretion. Percentage of spleen response and symptom response will be evaluated primarily. Participants' safety will be monitored throughout the study.
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome:

  • Percentage of participants who Achieve Greater than or equal to 35 percent (%) Reduction in Spleen Volume at Week 24 [ Time Frame: Week 24 ]
    Spleen response rate is defined as the percentage of participants who achieve >= 35% reduction in spleen volume at Week 24 from baseline as measured by imaging scans.
  • Percentage of participants who Achieve Greater than or equal to 50 percent (%) Reduction in Total Symptom Score (TSS) at Week 24 [ Time Frame: Week 24 ]
    Symptom response rate is defined as the percentage of participants who achieve >= 50% reduction in TSS at Week 24 from baseline as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) version 2.0 diary.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Complete remission (CR) or partial remission (PR) per modified 2013 IWG-MRT criteria [ Time Frame: up to 3 years ]
  • Clinical improvement (CI) per modified 2013 IWG-MRT criteria [ Time Frame: up to 3 years ]
  • Number of Participants with Responses per 2013 IWG-MRT [ Time Frame: up to 3 years ]
    Spleen response, symptoms response, and anemia response per modified 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) will be assessed.
  • Duration of Treatment Response and Remission [ Time Frame: up to 3 years ]
    Duration of spleen response, duration of symptoms response, duration of CR or PR, duration of CI, and duration of anemia response will be reported.
  • Overall Survival [ Time Frame: up to 3 years ]
    Overall survival is defined as the time from randomization to date of death from any cause.
  • European Organization for Research and treatment of Cancer (EORTC) QLQ-C30 Score [ Time Frame: up to 3 years ]
  • EuroQol-EQ-5D (EQ-5D-5L) Health Questionnaire Score [ Time Frame: up to 3 years ]
  • Brief Pain Inventory- Short Form (BPI) Score [ Time Frame: up to 3 years ]
  • Patient's Global Impression of Change (PGIC) [ Time Frame: up to 3 years ]
  • Number of Participants with Adverse Events (AEs) [ Time Frame: up to 3 years ]
  • Maximum Plasma Concentration (Cmax) of Imetelstat [ Time Frame: up to 3 years ]
    The Cmax is the maximum observed plasma concentration.
  • Time to Reach Maximum Concentration (tmax) of Imetelstat [ Time Frame: up to 3 years ]
    The tmax is time to reach the maximum observed plasma concentration.
  • Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24h]) of Imetelstat [ Time Frame: up to 3 years ]
    AUC 0-24h is area under the plasma concentration-time curve from time 0 to 24 hours postdose.
  • Elimination Half-Life (t [1/2] Lambda) of Imetelstat [ Time Frame: up to 3 years ]
    Elimination half-life (t [1/2] Lambda) is associated with the terminal slope (lambda [z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).


Original Secondary Outcome: Same as current

Information By: Janssen Research & Development, LLC

Dates:
Date Received: April 21, 2015
Date Started: June 2015
Date Completion: May 2019
Last Updated: October 31, 2016
Last Verified: October 2016