A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Imetelstat in Combination With Ruxolitinib in Participants With Myelofibrosis

NCT ID: NCT05371964

Last Updated: 2026-01-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-04

Study Completion Date

2028-08-31

Brief Summary

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The purpose of the study is to identify the recommended Part 2 dose (R2PD) of imetelstat sodium in combination with ruxolitinib in participants with myelofibrosis (MF) in Part 1, and to evaluate the safety and preliminary clinical activity of the R2PD of imetelstat sodium in combination with ruxolitinib in participants with MF in Part 2.

Detailed Description

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Conditions

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Myelofibrosis

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1: Imetelstat sodium + Ruxolitinib

Participants who have received ruxolitinib orally (PO) as part of standard of care (SOC) for at least 12 weeks prior to Screening will be enrolled. After enrollment, participants will initiate imetelstat sodium therapy. Dose levels of imetelstat sodium may include 4.7, 6, 7.5, 9.4 mg/kg, until a RP2D is established.

Group Type EXPERIMENTAL

Imetelstat sodium

Intervention Type DRUG

Imetelstat sodium will be administered as intravenous (IV) every 28 days.

Ruxolitinib

Intervention Type DRUG

Ruxolitinib will be administered, orally (PO), twice daily (BID) in cohort B as the standard of care per local prescribing guidelines.

Part 2: Imetelstat sodium + Ruxolitinib

Cohort A: Janus Kinase (JAK) inhibitor naive participants will receive initial treatment with ruxolitinib on study for at least 12 weeks, including 4 consecutive weeks at a stable dose, prior to the addition of imetelstat sodium. Participants can begin imetelstat sodium treatment after sponsor review and approval and meet the following requirements: platelet value is ≥75 x 10\^9/L for two consecutive measurements, at least 1 week apart, and the participant does not meet criteria for dose delay.

Note that the study will no longer recruit participants into Cohort A.

Cohort B: Participants will receive treatment with ruxolitinib for 12 weeks with at least 4 consecutive weeks at a stable dose prior to enrollment and will start combination treatment with imetelstat on study.

Group Type EXPERIMENTAL

Imetelstat sodium

Intervention Type DRUG

Imetelstat sodium will be administered as intravenous (IV) every 28 days.

Ruxolitinib

Intervention Type DRUG

Ruxolitinib will be administered, orally (PO), twice daily (BID) in cohort B as the standard of care per local prescribing guidelines.

Interventions

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Imetelstat sodium

Imetelstat sodium will be administered as intravenous (IV) every 28 days.

Intervention Type DRUG

Ruxolitinib

Ruxolitinib will be administered, orally (PO), twice daily (BID) in cohort B as the standard of care per local prescribing guidelines.

Intervention Type DRUG

Other Intervention Names

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GRN163L

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of primary myelofibrosis (PMF) according to the revised World Health Organization (WHO) criteria or post-essential thrombocythemia-MF or post-polycythemia vera according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria.
* Dynamic International Prognostic Scoring System (DIPSS) intermediate-1, intermediate-2 or high-risk MF.
* Candidate for ruxolitinib treatment:

* Part 1 participants: On ruxolitinib treatment for at least 12 weeks with at least 4 consecutive weeks immediately prior to enrollment at a stable dose.
* Part 2 participants: Candidate for ruxolitinib treatment as assessed by the investigator and has not previously been treated with a JAK inhibitor (Cohort A) OR currently receiving ruxolitinib per standard of care for at least 12 weeks with at least 4 consecutive weeks at a stable dose prior to enrollment (Cohort B). Note that the study will no longer recruit participants into Cohort A.
* Active symptoms of MF on the MFSAF v4.0 demonstrated by:

* Part 1 participants only: At least 2 symptoms with a score ≥ 1
* Part 2 participants only: At least 2 symptoms with a score of ≥ 3, or a total score of at least 10.
* Ineligible for or unwilling to undergo hematopoietic stem cell transplant at time of study entry.
* Hematology laboratory test values within protocol defined limits.
* Biochemical laboratory test values within protocol defined limits.
* Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2.
* Participants should follow protocol defined contraceptives procedures.
* A woman of childbearing potential must have a negative serum or urine pregnancy test at screening.

Exclusion Criteria

* Peripheral blood blast count of ≥10% or bone marrow blast count of ≥10%.
* Prior treatment with JAK inhibitor (except for participants being dosed optimized on ruxolitinib treatment prior to screening and enrollment in part 1 or Part 2 Cohort B).
* Known allergies, hypersensitivity, or intolerance to imetelstat or ruxolitinib or excipients.
* Prior treatment with imetelstat.
* Major surgery within 28 days prior to enrollment.
* Any investigational drug regardless of class or mechanism of action, hydroxyurea, chemotherapy, (except for ruxolitinib for participants being dose optimized prior to enrollment), immunomodulatory or immunosuppressive therapy, corticosteroids \>30 mg/day prednisone or equivalent ≤14 days prior to enrollment.
* Prior history of hematopoietic stem cell transplant.
* Diagnosis or treatment for malignancy other than MF, except:

* Malignancy treated with curative intent and with no known active disease present for ≥3 years before enrollment.
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
* Adequately treated cervical carcinoma in situ without evidence of disease.
* Clinically significant cardiovascular disease.
* Known history of human immunodeficiency virus (HIV) or any uncontrolled active systemic infection requiring IV antibiotics.
* Active systemic hepatitis infection requiring treatment or any known acute or chronic liver disease unless related to MF. Carriers of hepatitis virus are permitted to enter the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Geron Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michelle Mudge-Riley, DO

Role: STUDY_DIRECTOR

Geron Corporation

Locations

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City of Hope

Duarte, California, United States

Site Status RECRUITING

City of Hope

Irvine, California, United States

Site Status RECRUITING

University of Miami

Coral Gables, Florida, United States

Site Status RECRUITING

H. Lee Moffitt Cancer Center and Research Institute, Inc.

Tampa, Florida, United States

Site Status RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status RECRUITING

Texas Oncology

Denison, Texas, United States

Site Status WITHDRAWN

Texas Oncology

Tyler, Texas, United States

Site Status WITHDRAWN

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Michelle Mudge-Riley, DO

Role: CONTACT

650-473-7793

Judy Ho

Role: CONTACT

650-473-7793

Other Identifiers

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MYF1001

Identifier Type: -

Identifier Source: org_study_id

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