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

NCT02426086 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: CR10717063935937MYF20012015-000946-41
• Study Type: interventional
• Target: 107
• Locations: 11 countries
• Sites: 72

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of 2 dose regimens of imetelstat in participants with intermediate-2 or high-risk myelofibrosis (MF) whose disease is relapsed after or is refractory to Janus Kinase (JAK) inhibitor treatment. Key secondary endpoint includes overall survival.

Conditions

Myelofibrosis

Keywords

Myelofibrosis; Imetelstat; GRN163L; Relapsed/refractory to JAKi; IMbark

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Spleen Response

  Spleen response rate is defined as the percentage of participants who achieved ≥ 35% reduction in spleen volume at Week 24 from baseline performed by the IRC using magnetic resonance imaging (MRI).

  Week 24

• Percentage of Participants With Symptom Response

  Symptom response rate is defined as percentage of participants who achieved ≥ 50% reduction in total symptom score (TSS) at Week 24 from baseline as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) version 2.0 diary. The MFSAF assessed following symptoms due to Myelofibrosis (MF): night sweats, itchiness, abdominal discomfort, pain under ribs on left side, feeling of fullness, bone or muscle pain and degree of inactivity. Each item is scored on a scale of 0 (absent) to 10 (worst imaginable) with higher scores indicating more severe symptoms and greater inactivity. The total score ranges from 0-70, where 0 indicates absent/as good as it can be and 70 indicates worst imaginable/as bad as it can be.

  Week 24

Secondary Outcomes (20)

• Percentage of Participants With Overall Response as Per Modified 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria

  Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

• Percentage of Participants With Clinical Improvement (CI) Per Modified 2013 IWG-MRT Criteria

  Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

• Percentage of Participants With Clinical Response Per Modified 2013 IWG-MRT

  Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

• Percentage of Participants With Spleen Response Per Modified 2013 IWG-MRT Criteria

  Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

• Percentage of Participants With Symptoms Response Per Modified 2013 IWG-MRT Criteria

  Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

Study Arms (2)

Imetelstat 4.7 mg/kg

EXPERIMENTAL

Drug: Imetelstat 4.7 mg/kg

Imetelstat 9.4 mg/kg

EXPERIMENTAL

Drug: Imetelstat 9.4 mg/kg

Interventions

Imetelstat 4.7 mg/kg DRUG

Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle. Study drug was administered intravenously until disease progression, unacceptable toxicity, or study end.

Imetelstat 4.7 mg/kg

Imetelstat 9.4 mg/kg DRUG

Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end.

Imetelstat 9.4 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of primary myelofibrosis (PMF) according to the revised WHO criteria; or post-essential thrombocythemia-myelofibrosis (PET-MF) or post-polycythemia vera-myelofibrosis (PPV-MF) according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria.
• Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or highrisk MF.
• Measurable splenomegaly prior to study entry as demonstrated by palpable spleen measuring ≥ 5 cm below the left costal margin OR spleen volume of ≥ 450 cm\^3 measured by magnetic resonance imaging (MRI).
• Active symptoms of MF as demonstrated by a symptom score of at least 5 points (on a 0 to 10 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 Janus kinase (JAK) inhibitor therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.

You may not qualify if:

• Peripheral blood blast count of ≥ 10% or bone marrow blast count of ≥ 10%.
• Prior treatment with imetelstat.
• Any chemotherapy or MF-directed therapy, investigational drug, hydroxyurea, immunomodulatory or immunosuppressive therapy, corticosteroids or JAK inhibitor therapy ≤14 days prior to randomization.
• 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.

Sponsors & Collaborators

• Geron Corporation: lead

Study Sites (72)

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Birmingham, Alabama, United States

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Duarte, California, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Stanford, California, United States

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Washington D.C., District of Columbia, United States

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Tampa, Florida, United States

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West Palm Beach, Florida, United States

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Chicago, Illinois, United States

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Louisville, Kentucky, United States

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Baltimore, Maryland, United States

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Ann Arbor, Michigan, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Buffalo, New York, United States

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Lake Success, New York, United States

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New York, New York, United States

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The Bronx, New York, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Greenville, South Carolina, United States

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Watertown, South Dakota, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Seattle, Washington, United States

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Milwaukee, Wisconsin, United States

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Antwerp, Belgium

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Bruges, Belgium

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Brussels, Belgium

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Leuven, Belgium

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Edmonton, Alberta, Canada

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Winnipeg, Manitoba, Canada

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Montreal, Quebec, Canada

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Angers, France

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Lille, France

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Marseille, France

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Paris, France

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Pierre-Bénite, France

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Toulouse, France

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Aachen, Germany

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Cologne, Germany

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Dresden, Germany

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Düsseldorf, Germany

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Frankfurt, Germany

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Hamburg, Germany

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Heidelberg, Germany

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Leipzig, Germany

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Mannheim, Germany

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Rostock, Germany

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Haifa, Israel

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Jerusalem, Israel

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Kfar Saba, Israel

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Nahariya, Israel

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Ramat Gan, Israel

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Tel Aviv, Israel

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Bergamo, Italy

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Bologna, Italy

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Seoul, South Korea

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Barcelona, Spain

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Las Palmas de Gran Canaria, Spain

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Madrid, Spain

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Salamanca, Spain

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Valencia, Spain

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Chiayi City, Taiwan

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Taipei, Taiwan

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Birmingham, United Kingdom

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Glasgow, United Kingdom

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London, United Kingdom

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Oxford, United Kingdom

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Related Publications (1)

• Mascarenhas J, Komrokji RS, Palandri F, Martino B, Niederwieser D, Reiter A, Scott BL, Baer MR, Hoffman R, Odenike O, Vannucchi AM, Bussolari J, Zhu E, Rose E, Sherman L, Dougherty S, Sun L, Huang F, Wan Y, Feller FM, Rizo A, Kiladjian JJ. Randomized, Single-Blind, Multicenter Phase II Study of Two Doses of Imetelstat in Relapsed or Refractory Myelofibrosis. J Clin Oncol. 2021 Sep 10;39(26):2881-2892. doi: 10.1200/JCO.20.02864. Epub 2021 Jun 17.

  PMID: 34138638 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis; Recurrence

Interventions

imetelstat

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Geron Corp.

myf2001-info@geron.com

650-473-7700

Study Officials

• Study Clinical Team

  Geron Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Initially single-blind; treatments unmasked after 1st Interim Analysis and continued as open-label treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2015
• First Posted: April 24, 2015
• Study Start: August 28, 2015
• Primary Completion: April 26, 2018
• Study Completion: February 7, 2020
• Last Updated: September 14, 2021
• Results First Posted: September 14, 2021

Record last verified: 2021-08

Locations

TW (2); GB (4); BE (4); DE (10); IT (2); US (29); IL (6); ES (5); FR (6); CA (3); KR (1)