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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

This study has suspended participant recruitment.
(Current participants remain active and on study treatment; new enrollment may resume pending collection/review of more mature data)
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02426086
First received: April 21, 2015
Last updated: October 31, 2016
Last verified: October 2016
  Purpose
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.

Condition Intervention Phase
Primary Myelofibrosis Drug: Imetelstat 9.4 milligram/kilogram (mg/kg) Drug: Imetelstat 4.7 mg/kg Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 (MF) Relapsed/Refractory to Janus Kinase (JAK) Inhibitor

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Estimated Enrollment: 160
Study Start Date: June 2015
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imetelstat 9.4 milligram/kilogram (mg/kg)
Participants will receive imetelstat intravenously as 9.4 mg/kg every 3 weeks. Study drug will be administered intravenously until disease progression, unacceptable toxicity, or study end.
Drug: Imetelstat 9.4 milligram/kilogram (mg/kg)
Participants will receive imetelstat intravenously as 9.4 mg/kg every 3 weeks. Study drug will be administered intravenously until disease progression, unacceptable toxicity, or study end.
Experimental: Imetelstat 4.7 mg/kg
Participants will receive imetelstat intravenously as 4.7 mg/kg every 3 weeks. Study drug will be administered intravenously until disease progression, unacceptable toxicity, or study end. Participants will have an option to continue the treatment at the current dose or at an escalated dose of 9.4 mg/kg based on investigator's discretion.
Drug: Imetelstat 4.7 mg/kg
Participants will receive imetelstat intravenously as 4.7 mg/kg every 3 weeks or at an escalated dose of 9.4 mg/kg based on investigator's discretion. Study drug will be administered intravenously until disease progression, unacceptable toxicity, or study end.

Detailed Description:
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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of PMF according to the revised WHO criteria; or PET-MF or PPV-MF according to the IWG-MRT criteria
  • DIPSS intermediate-2 or high risk MF
  • Measurable splenomegaly prior to study entry as demonstrated by palpable spleen measuring greater than or equal to (>=) 5 cm below the left costal margin OR spleen volume of >= 450 cm^3 measured by MRI
  • Active symptoms of MF as demonstrated by a symptom score of at least 5 points (on a 0 to10 scale) on at least one of the symptoms or a score of 3 or greater on at least 2 of the symptoms
  • Documented progressive disease during or after JAK inhibitor therapy
  • ECOG performance status 0, 1 or 2

Exclusion Criteria:

  • Peripheral blood blast count of >= 10% or bone marrow blast count of >=10%
  • Prior treatment with imetelstat
  • Major surgery within 4 weeks prior to randomization
  • Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), of any type or known acute or chronic liver disease including cirrhosis
  • Prior history of hematopoietic stem cell transplant
  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: NCT02426086

  Show 72 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02426086     History of Changes
Other Study ID Numbers: CR107170
63935937MYF2001 ( Other Identifier: Janssen Research & Development, LLC )
2015-000946-41 ( EudraCT Number )
Study First Received: April 21, 2015
Last Updated: October 31, 2016

Keywords provided by Janssen Research & Development, LLC:
Myelofibrosis
JNJ-63935937
Imetelstat

Additional relevant MeSH terms:
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Niacinamide
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 18, 2017