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Study to Evaluate Imetelstat (GRN163L) in Subjects With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

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ClinicalTrials.gov Identifier: NCT02598661
Recruitment Status : Recruiting
First Posted : November 6, 2015
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
Geron Corporation

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: Imetelstat Drug: Placebo Phase 2 Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects With IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) That is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
Actual Study Start Date : November 24, 2015
Estimated Primary Completion Date : August 15, 2022
Estimated Study Completion Date : May 15, 2023

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1: Imetelstat
Imetelstat 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.
 Drug: Imetelstat
Imetelstat 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.
Experimental: Part 2: Imetelstat
Imetelstat 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.
 Drug: Imetelstat
Imetelstat 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.
Placebo Comparator: Part 2: Placebo
Matching Placebo to Imetelstat will be administered.
 Drug: Placebo
Matching Placebo to Imetelstat will be administered.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of participants without any red blood cell (RBC) transfusion during any consecutive 8 week period [ Time Frame: During study (approximately 2 years) ]

Secondary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) [ Time Frame: During study (approximately 2 years) ]
  2. Percentage of participants without any red blood cell (RBC) transfusion during any consecutive 24 week period [ Time Frame: During study (approximately 2 years) ]
  3. Time to the 8-week RBC transfusion independence (TI) [ Time Frame: During study (approximately 2 years) ]
  4. Duration of RBC TI [ Time Frame: During study (approximately 2 years) ]
  5. Percentage of Participants with hematologic improvement [ Time Frame: During study (approximately 2 years) ]
  6. 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) ]
  7. Overall survival [ Time Frame: During study (approximately 2 years) ]
  8. Progression Free Survival (PFS) [ Time Frame: During study (approximately 2 years) ]
    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.

  9. Time to Progression to Acute Myeloid Leukemia [ Time Frame: During study (approximately 2 years) ]
  10. Percentage of Participants with Transfusion [ Time Frame: During study (approximately 2 years) ]
  11. Amount of Transfusions [ Time Frame: During study (approximately 2 years) ]
  12. Percentage of Participants receiving any myeloid growth factors [ Time Frame: During study (approximately 2 years) ]
  13. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: During study (approximately 2 years) ]
  14. Area under the drug concentration-plasma time curve from time zero to last measurable concentration (AUC0-t) [ Time Frame: During study (approximately 2 years) ]
  15. Percentage of Participants with antibodies to imetelstat [ Time Frame: During study (approximately 2 years) ]
  16. Medical Resource Utilization Data in Part 2 [ Time Frame: During study (approximately 2 years) ]
  17. Assessment of Functional Assessment of Cancer Therapy- Anemia-Related Effects (FACT-An) in Part 2 [ Time Frame: During study (approximately 2 years) ]
    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.

  18. Assessment of EuroQol 5 Dimension Questionnaire (EQ-5D-5L) in Part 2 [ Time Frame: During study (approximately 2 years) ]
    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).

  19. Assessment of Quality of Life in Myelodysplasia Scale (QUALMS) in Part 2 [ Time Frame: During study (approximately 2 years) ]
    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.

  20. Assessment of Participant Global Impression of Change (PGIC) in Part 2 [ Time Frame: During study (approximately 2 years) ]
    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".

  21. Change From Baseline in QTc Interval at Day 1 of Part 2 [ Time Frame: Baseline and Day 1 ]
    Change from baseline in QTc interval by Fridericia's correction method (ΔQTcF) will be assessed in part 2.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02598661


Contacts
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Contact: Faye Feller, MD mds3001-info@Geron.com
Contact: Souria Dougherty mds3001-info@Geron.com

Locations
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Sponsors and Collaborators
Geron Corporation
Investigators
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Study Director: Faye Feller, MD Geron Corporation
More Information
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Responsible Party: Geron Corporation
ClinicalTrials.gov Identifier: NCT02598661    
Other Study ID Numbers: CR107947
63935937MDS3001 ( Other Identifier: Geron Corporation )
2015-002874-19 ( EudraCT Number )
First Posted: November 6, 2015    Key Record Dates
Last Update Posted: August 11, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Geron Corporation:
Myelodysplastic Syndromes
Imetelstat
GRN163L
 Relapsed/refractory to ESAs
Transfusion dependent
IMerge
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
 Precancerous Conditions
Neoplasms
Imetelstat
Motesanib diphosphate
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors