Clinical Trials /

Study to Evaluate Imetelstat (JNJ-63935937) in Subjects With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

NCT02598661

Description:

The purpose of this study is to evaluate the efficacy and safety of imetelstat in transfusion dependent participants with low or intermediate-1 risk myelodysplastic syndrome (MDS) that is relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate Imetelstat (JNJ-63935937) in Subjects With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
  • Official Title: A Study to Evaluate Imetelstat (JNJ-63935937) in Transfusion-Dependent Subjects With IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) That is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment

Clinical Trial IDs

  • ORG STUDY ID: CR107947
  • SECONDARY ID: 63935937MDS3001
  • SECONDARY ID: 2015-002874-19
  • NCT ID: NCT02598661

Conditions

  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
ImetelstatPart 1: Imetelstat
PlaceboPart 2: Placebo

Purpose

The purpose of this study is to evaluate the efficacy and safety of imetelstat in transfusion dependent participants with low or intermediate-1 risk myelodysplastic syndrome (MDS) that is relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment.

Detailed Description

      This is a Phase 2/3, multicenter study of imetelstat that consists of 2 parts. Part 1 is an
      open‐label, single-arm design to assess the efficacy and safety of imetelstat. Approximately
      55 participants will be enrolled in Part 1, including the expansion cohort, and be
      followed-up for safety, hematologic improvement and reduction in transfusion requirement.
      Part 2 of the study will be initiated if data from Part 1 are supportive of a satisfactory
      benefit/risk profile. Part 2 is a double‐blind, randomized design to compare the efficacy of
      imetelstat with placebo. Approximately 170 eligible participants will be randomized in a 2:1
      ratio to receive either imetelstat or placebo, respectively. Each part of the study will
      consist of 3 phases: a Screening phase (up to 28 days); a treatment phase; and a
      post-treatment follow-up phase which will continue until death, lost to follow-up, withdrawal
      of consent, or the End of the Study (whichever occurs first). The End of the Study is defined
      as 2 years after the study entry of the last participant or anytime the sponsor terminates
      the study, whichever comes first.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: ImetelstatExperimentalImetelstat will be administered at a starting dose of 7.5 milligram per kilogram (mg/kg) given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.
  • Imetelstat
Part 2: ImetelstatExperimentalImetelstat will be administered at a starting dose of 7.5 milligram per kilogram (mg/kg) given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.
  • Imetelstat
Part 2: PlaceboPlacebo ComparatorMatching Placebo to Imetelstat will be administered.
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Man or woman greater than or equal to (>=) 18 years of age

          -  In Part 1, diagnosis of myelodysplastic syndrome (MDS) according to World Health
             Organization (WHO) criteria

          -  International Prognostic Scoring System (IPSS) low Risk or intermediate-1 risk MDS

          -  Red blood cell (RBC) transfusion dependent, defined as requiring at least 4 RBC units
             transfused over an 8-week period during the 16 weeks prior to Study Entry;
             pre-transfusion hemoglobin (Hb) should be less than or equal to 9.0 gram per deciliter
             (g/dL) to count towards the 4 units total

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

        Exclusion Criteria:

          -  Participant has known allergies, hypersensitivity, or intolerance to imetelstat or its
             excipients

          -  Participant has received an investigational drug or used an invasive investigational
             medical device within 30 days prior to Study Entry or is currently enrolled in an
             investigational study

          -  Prior treatment with imetelstat

          -  Have received corticosteroids greater than (>) 30 milligram per day (mg/day)
             prednisone or equivalent, or growth factor treatment within 4 weeks prior to study
             entry

          -  a) Prior treatment with a hypomethylating agent (example [eg], azacitidine,
             decitabine); b) Prior treatment with lenalidomide; c) Has received an
             erythropoiesis-stimulating agent (ESA) or any chemotherapy, immunomodulatory, or
             immunosuppressive therapy within 4 weeks prior to study entry (8 weeks for long-acting
             ESAs)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of participants without any red blood cell (RBC) transfusion during any consecutive 8 week period
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of Participants with Adverse Events (AEs)
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Percentage of participants without any red blood cell (RBC) transfusion during any consecutive 24 week period
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Time to the 8-week RBC transfusion independence (TI)
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Duration of RBC TI
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Percentage of Participants with hematologic improvement
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Complete remission (CR) or Partial remission (PR) as Per International Working Group (IWG) Response Criteria 2006
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Overall survival
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:Progression free survival will be assessed as the time interval from study Day 1 to the first date of disease progression or death from any cause, whichever occurs first. As per IWG criteria disease progression is defined as: at least one of the following: at least 50 percent (%) decrement from maximum response levels in granulocytes or platelets; reduction in hemoglobin by greater than or equal to (>=) 1.5 gram per deciliter (g/dL); transfusion dependence.
Measure:Time to Progression to Acute Myeloid Leukemia
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Transfusion
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Amount of Transfusions
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Percentage of Participants receiving any myeloid growth factors
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Maximum Observed Plasma Concentration (Cmax)
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Area under the drug concentration-plasma time curve from time zero to last measurable concentration (AUC0-t)
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Percentage of Participants with antibodies to imetelstat
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Medical Resource Utilization Data in Part 2
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:
Measure:Assessment of Functional Assessment of Cancer Therapy- Anemia-Related Effects (FACT-An) in Part 2
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:The Functional Assessment of Cancer Therapy Anemia (FACT-An), is included in order to provide an assessment of the subject's functional status, well-being, and symptoms over time.
Measure:Assessment of EuroQol 5 Dimension Questionnaire (EQ-5D-5L) in Part 2
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:The EQ-5D-5L is a generic measure of health status. EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Measure:Assessment of Quality of Life in Myelodysplasia Scale (QUALMS) in Part 2
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:The QUALMS is a 38-item measure that assesses health-related quality of life for patients with MDS. Thirty-three items are used to calculate the total score, as well as the 14 item physical burden (QUALMS-P), 3-item benefit-finding (QUALMS-BF), and 11-item emotional burden (QUALMS-E) subscales.
Measure:Assessment of Participant Global Impression of Change (PGIC) in Part 2
Time Frame:During study (approximately 2 years)
Safety Issue:
Description:The Participant Global Impression of Change (PGIC) is a single-item questionnaire designed to provide an overall assessment of treatment from the participant's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of "very much improved" or "much improved".
Measure:Change From Baseline in QTc Interval at Day 1 of Part 2
Time Frame:Baseline and Day 1
Safety Issue:
Description:Change from baseline in QTc interval by Fridericia's correction method (ΔQTcF) will be assessed in part 2.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Trial Keywords

  • Myelodysplastic Syndromes
  • Imetelstat

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