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 is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02426086
First received: April 21, 2015
Last updated: July 11, 2016
Last verified: July 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
Myelofibrosis
Drug: Imetelstat 9.4 milligram/kilogram (mg/kg)
Drug: Imetelstat 4.7 mg/kg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Clinical improvement (CI) per modified 2013 IWG-MRT criteria [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Number of Participants with Responses per 2013 IWG-MRT [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • EuroQol-EQ-5D (EQ-5D-5L) Health Questionnaire Score [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Brief Pain Inventory- Short Form (BPI) Score [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Patient's Global Impression of Change (PGIC) [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Number of Participants with Adverse Events (AEs) [ Time Frame: up to 3 years ] [ Designated as safety issue: Yes ]
  • Maximum Plasma Concentration (Cmax) of Imetelstat [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    The Cmax is the maximum observed plasma concentration.

  • Time to Reach Maximum Concentration (tmax) of Imetelstat [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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: 200
Study Start Date: June 2015
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: November 2017 (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.
Drug: 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.

Detailed Description:
This is a randomized (study medication assigned to participants by chance), single-blind (a medical research study in which the person giving the treatment, but not the participant, knows which treatment the participant is receiving) and 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. Approximately 200 participants will be enrolled in this study with approximately 100 participants per treatment arm. 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). All the eligible participants will be randomly assigned to 1 of 2 arms. 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. 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)
Genders Eligible for Study:   Both
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

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 76 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02426086     History of Changes
Other Study ID Numbers: CR107170  63935937MYF2001 
Study First Received: April 21, 2015
Last Updated: July 11, 2016
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
Canada: Health Canada - TPD
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Great Britain: Medicines and Healthcare Products Regulatory Agency
Israel: Israeli Health Ministry Pharmaceutical Administration
South Korea: Ministry of Food and Drug Safety
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
Taiwan: Ministry of Health and Welfare
United States: Food and Drug Administration
Republic of Korea: Ministry of Food and Drug Safety

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

Additional relevant MeSH terms:
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on July 26, 2016