A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment

Running, not enrolling · Phase 3

Conditions studied: Myelofibrosis

In brief

The purpose of the study is to evaluate the overall survival of participants treated with imetelstat compared to best available therapy with intermediate-2 or high-risk Myelofibrosis (MF) who are relapsed/refractory (R/R) to Janus Kinase (JAK)-Inhibitor treatment.

Key facts

Study ID: NCT04576156
Run by: Geron Corporation
People needed: 327
Starts: 2021-04-12
Expected to finish: 2028-06-30
Last updated by the study team: 2026-07-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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:
no decrease in spleen volume (< 10% by MRI or CT) from the start of treatment with JAK-inhibitor
no decrease in spleen size (< 30% by palpation or length by imaging) from the start of treatment with JAK-inhibitor
no decrease in symptoms (< 20% by Myelofibrosis Symptom Assessment Form [MFSAF] or myeloproliferative neoplasm SAF) from the start of treatment with JAK-inhibitor
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
Increase in spleen volume from time of best response by 25% measured by MRI or CT, or
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

You may not qualify if…

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 it is running

UCLA David Geffen School of Medicine — Los Angeles, California, United States
Smilow Cancer Center at YNHH — New Haven, Connecticut, United States
BRCR Medical Center Inc — Plantation, Florida, United States
University of South Florida — Tampa, Florida, United States
Norton Cancer Institute — Louisville, Kentucky, United States
Icahn School of Medicine at Mount Sinai — New York, New York, United States
Duke University Medical Center — Durham, North Carolina, United States
Gabrail Cancer Center — Canton, Ohio, United States
Prairie Lakes Health Care System, Inc. — Watertown, South Dakota, United States
The University of Texas MD — Houston, Texas, United States
Northwest Medical Specialties PLLC — Seattle, Washington, United States
Hospital Aleman — Ciudad de Buenos Aires, Buenos Aires, Argentina
Sanatorio de la Mujer — Rosario, Santa Fe Province, Argentina
Sanatorio Allende — Córdoba, Argentina
Royal North Shore Hospital — St Leonards, New South Wales, Australia
Royal Brisbane and Women's Hospital — Herston, Queensland, Australia
Royal Hobart Hospital — Hobart, Tasmania, Australia
Epworth Healthcare — Richmond, Victoria, Australia
Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhügel — Wein, Burgenland, Austria
Krankenhaus der Elisabethinen — Linz, Upper Austria, Austria
Kepler Universitätsklinikum Gm — Linz, Upper Austria, Austria
Klinikum Wels-Grieskirchen GmbH — Wels, Upper Austria, Austria
AZ Klina — Antwerp, Antwerpen, Belgium
UZ Antwerpen — Edegem, Antwerpen, Belgium
University of California-San Diego/Moores UCSD Cancer Center — La Jolla, California, United States

Full record on ClinicalTrials.gov

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