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

NCT05371964 | Recruiting Phase 1 FDA Drug

• 1 other identifier: MYF1001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Myelofibrosis

Outcome Measures

Primary Outcomes (3)

• Part 1: Incidence, Type, and Severity of Adverse Events, Including Dose-limiting Toxicity (DLT) During the DLT Observation Period and/or Study Treatment

  28 days after first dose

• Part 2: Number of Participants With Treatment-emergent Adverse Event (AE)

  Safety will be assessed based on incidence and severity (according to Common Terminology Criteria for Adverse Events) of treatment emergent adverse events from the first dose of study treatment until 30 days after completion of treatment.

  First dose of study treatment until 30 days after the last dose of study treatment (up to approximately 5 years)

• Part 2: Symptom Response Rate at Week 24

  Symptom response rate is defined as percentage of participants with \>=50% reduction in the Total Symptom Score (TSS) measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 e-diary at 24 week compared to baseline.

  Week 24

Secondary Outcomes (15)

• Part 1: Pharmacokinetic Profile of Ruxolitinib (Maximum Observed Plasma Concentration [Cmax]

  From first dose of Ruxolitinib treatment up to approximately 5 years

• Part 1: Pharmacokinetic Profile of Ruxolitinib Time to Reach Maximum Plasma Concentration [Tmax])

  From first dose of imetelstat treatment up to approximately 5 years

• Part 1 and Part 2: Pharmacokinetic Profile of Imetelstat Sodium Maximum Observed Plasma Concentration [Cmax]

  From first dose of imetelstat treatment up to approximately 5 years

• Part 1 and Part 2: Pharmacokinetic Profile of Imetelstat Time to Reach Maximum Plasma Concentration [Tmax])

  From first dose of imetelstat treatment up to approximately 5 years

• Part 1 and Part 2: Percentage of Participants with Anti-imetelstat Antibodies

  From first dose of imetelstat treatment up to approximately 5 years

Study Arms (2)

Part 1: Imetelstat sodium + Ruxolitinib

EXPERIMENTAL

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.

Drug: Imetelstat sodium; Drug: Ruxolitinib

Part 2: Imetelstat sodium + Ruxolitinib

EXPERIMENTAL

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.

Drug: Imetelstat sodium; Drug: Ruxolitinib

Interventions

Imetelstat sodium DRUG

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

Also known as: GRN163L

Part 1: Imetelstat sodium + Ruxolitinib; Part 2: Imetelstat sodium + Ruxolitinib

Ruxolitinib DRUG

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

Part 1: Imetelstat sodium + Ruxolitinib; Part 2: Imetelstat sodium + Ruxolitinib

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Geron Corporation: lead

Study Sites (8)

City of Hope

Duarte, California, 91010, United States

RECRUITING

City of Hope

Irvine, California, 92618, United States

RECRUITING

University of Miami

Coral Gables, Florida, 33146, United States

RECRUITING

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

Tampa, Florida, 33612, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Texas Oncology

Denison, Texas, 75020, United States

WITHDRAWN

Texas Oncology

Tyler, Texas, 75702, United States

WITHDRAWN

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

imetelstat; GRN163L peptide; ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Michelle Mudge-Riley, DO

  Geron Corporation

  STUDY DIRECTOR

Central Study Contacts

Michelle Mudge-Riley, DO

CONTACT

650-473-7793; myf1001-info@geron.com

Judy Ho

CONTACT

650-473-7793; myf1001-info@geron.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2022
• First Posted: May 12, 2022
• Study Start: May 4, 2022
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)