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

NCT ID: NCT02426086

Last Updated: 2021-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-28
• Study Completion Date: 2020-02-07

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.

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. The main study consists of 3 parts: Screening Phase (21 days before randomization); 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 received imetelstat 9.4 milligram (mg)/kilogram (kg) intravenously (IV) for every 3 weeks until disease progression, unacceptable toxicity, or study end OR imetelstat 4.7 mg/kg IV for every 3 weeks until disease progression, unacceptable toxicity, or study end. Initially, all participants were blinded to the treatment. After the first interim analysis, treatment for all participants was unblinded and participants assigned to the imetelstat 4.7 mg/kg arm could continue with their same imetelstat dose or have it increased to 9.4 mg/kg at the investigator's discretion. The percentage of spleen response and symptom response were evaluated as co-primary endpoints. Following completion of the primary analysis, participants benefiting from study treatment could continue to receive imetelstat in Extension phase for up to 2 years or until loss of benefit or unacceptable toxicity. Participants who had already stopped study treatment could enter the Extension phase to continue follow up for safety via serious adverse event collection and for survival status.

Conditions

Myelofibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Imetelstat 4.7 mg/kg

Group Type: EXPERIMENTAL

Imetelstat 4.7 mg/kg

Intervention Type: 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 9.4 mg/kg

Group Type: EXPERIMENTAL

Imetelstat 9.4 mg/kg

Intervention Type: 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.

Interventions

Imetelstat 4.7 mg/kg

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.

Intervention Type: DRUG

Imetelstat 9.4 mg/kg

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Geron Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Clinical Team

Role: STUDY_DIRECTOR

Geron Corporation

Locations

Birmingham, Alabama, United States

Duarte, California, United States

La Jolla, California, United States

Los Angeles, California, United States

Stanford, California, United States

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

Tampa, Florida, United States

West Palm Beach, Florida, United States

Chicago, Illinois, United States

Louisville, Kentucky, United States

Baltimore, Maryland, United States

Ann Arbor, Michigan, United States

Rochester, Minnesota, United States

St Louis, Missouri, United States

Buffalo, New York, United States

Lake Success, New York, United States

New York, New York, United States

The Bronx, New York, United States

Charlotte, North Carolina, United States

Durham, North Carolina, United States

Winston-Salem, North Carolina, United States

Cincinnati, Ohio, United States

Philadelphia, Pennsylvania, United States

Greenville, South Carolina, United States

Watertown, South Dakota, United States

Nashville, Tennessee, United States

Dallas, Texas, United States

Seattle, Washington, United States

Milwaukee, Wisconsin, United States

Antwerp, , Belgium

Bruges, , Belgium

Brussels, , Belgium

Leuven, , Belgium

Edmonton, Alberta, Canada

Winnipeg, Manitoba, Canada

Montreal, Quebec, Canada

Angers, , France

Lille, , France

Marseille, , France

Paris, , France

Pierre-Bénite, , France

Toulouse, , France

Aachen, , Germany

Cologne, , Germany

Dresden, , Germany

Düsseldorf, , Germany

Frankfurt, , Germany

Hamburg, , Germany

Heidelberg, , Germany

Leipzig, , Germany

Mannheim, , Germany

Rostock, , Germany

Haifa, , Israel

Jerusalem, , Israel

Kfar Saba, , Israel

Nahariya, , Israel

Ramat Gan, , Israel

Tel Aviv, , Israel

Bergamo, , Italy

Bologna, , Italy

Seoul, , South Korea

Barcelona, , Spain

Las Palmas de Gran Canaria, , Spain

Madrid, , Spain

Salamanca, , Spain

Valencia, , Spain

Chiayi City, , Taiwan

Taipei, , Taiwan

Birmingham, , United Kingdom

Glasgow, , United Kingdom

London, , United Kingdom

Oxford, , United Kingdom

Countries

United States; Belgium; Canada; France; Germany; Israel; Italy; South Korea; Spain; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34138638 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

63935937MYF2001

Identifier Type: OTHER

Identifier Source: secondary_id

2015-000946-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR107170

Identifier Type: -

Identifier Source: org_study_id