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Comparing Imetelstat to Best Available Therapy for Myelofibrosis

A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat (GRN163L) Versus Best Available Therapy (BAT) in Patients With Intermediate-2 or High-risk Myelofibrosis (MF) Relapsed / Refractory (R/R) to Janus Kinase (JAK) Inhibitor

Phase 3 Interventional Geron Corporation · NCT04576156

This study is testing if a new drug called imetelstat can help people with myelofibrosis who haven't improved with standard treatments live longer compared to the best available therapy.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment320 (estimated)
Ages18 Years and up
SexAll
SponsorGeron Corporation Industry-sponsored
Drugs / interventionsruxolitinib, chemotherapy, prednisone
Locations215 sites (La Jolla, California and 214 other locations)
Trial IDNCT04576156 on ClinicalTrials.gov

What this trial studies

This multicenter Phase 3 trial evaluates the overall survival of patients with intermediate-2 or high-risk myelofibrosis who have not responded to Janus Kinase (JAK)-inhibitor treatment. Participants will undergo a screening phase followed by randomization into two arms: one receiving imetelstat and the other receiving the best available therapy. The study includes a treatment phase and a post-treatment follow-up phase to monitor outcomes until death or study end. Patients who show progressive disease while on best available therapy may have the option to crossover to imetelstat treatment.

Who should consider this trial

Good fit: Ideal candidates are individuals diagnosed with primary myelofibrosis or post-essential thrombocythemia/polycythemia vera myelofibrosis who are relapsed/refractory to JAK-inhibitor treatment.

Not a fit: Patients who are not relapsed/refractory to JAK-inhibitor treatment or those eligible for allogeneic stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with myelofibrosis who have not responded to existing therapies.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific comparison of imetelstat to best available therapy is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Diagnosis of primary myelofibrosis according to the revised World Health Organization criteria or post-essential thrombocythemia-MF or post-polycythemia vera-MF according to the IWG-MRT criteria
* Dynamic International Prognostic Scoring System intermediate-2 or high-risk MF
* Relapsed/refractory to JAK-inhibitor treatment as defined in either inclusion (i), (ii) or (iii) and not eligible for allogeneic stem cell transplantation (ASCT) at screening:

  * (i) Treatment with JAK-inhibitor for \>= 6 months duration, including at least 2 months at an optimal dose as assessed by the investigator for that participant and at least one of the following:

    1. no decrease in spleen volume (\< 10% by MRI or CT) from the start of treatment with JAK-inhibitor
    2. no decrease in spleen size (\< 30% by palpation or length by imaging) from the start of treatment with JAK-inhibitor
    3. no decrease in symptoms (\< 20% by Myelofibrosis Symptom Assessment Form \[MFSAF\] or myeloproliferative neoplasm SAF) from the start of treatment with JAK-inhibitor
    4. a score of at least 15 on TSS assessed using the MFSAF v4.0 during screening.
  * (ii) Treatment with JAK-inhibitor treatment for\>= 3 months duration with maximal doses (e.g., 20-25 mg twice daily ruxolitinib) for that participant and no decrease in spleen volume/size or symptoms as defined in inclusion criterion (i \[a, b, or c\]).
  * (iii) Following maximum tolerated doses of JAK inhibitor therapy for ≥3 months duration, having documented relapsed disease defined as either

    1. Increase in spleen volume from time of best response by 25% measured by MRI or CT, or
    2. Increase in spleen size by palpation, CT, or ultrasound

       * (b.i) For splenomegaly of 5-10 cm at the start of JAK inhibitor treatment, at least 100% increase in palpable spleen size from time of best response;
       * (b.ii) For splenomegaly of \> 10 cm at the start of JAK inhibitor treatment, at least 50% increase in palpable spleen size from time of best response;

AND not a candidate for further JAK inhibitor at screening per investigator.

* Measurable splenomegaly demonstrated by a palpable spleen measuring \>= 5 cm below the left costal margin or a spleen volume \>= 450 cm\^3 by MRI or CT
* Active symptoms of MF on the MFSAF v4.0 demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale)
* Hematology laboratory test values within the protocol defined limits
* Biochemical laboratory test values must be 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%
* Known allergies, hypersensitivity, or intolerance to imetelstat or its excipients
* Prior treatment with imetelstat
* Any chemotherapy or MF directed therapy, including investigational drug regardless of class or mechanism of action, immunomodulatory or immunosuppressive therapy, corticosteroids greater than 30 mg/day prednisone or equivalent, and JAK-inhibitor treatment less than equal to 14 days prior to randomization
* 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 randomization
  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  * Adequately treated cervical carcinoma in situ without evidence of disease
* Known history of human immunodeficiency virus or any uncontrolled active systemic infection requiring IV antibiotics
* Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), or any known acute or chronic liver disease requiring treatment unless related to underlying hepatosplenomegaly due to MF
* Major surgery within 28 days prior to randomization
* Any life-threatening illness (e.g., coronavirus disease-2019), medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety, interfere with the imetelstat metabolism, or put the study outcomes at undue risk

Where this trial is running

La Jolla, California and 214 other locations

+165 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions MyelofibrosisMyeloproliferative neoplasmsPolycythemiaThrombocythemiaPrimary myelofibrosisJanus Kinase-Inhibitor
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.