ACTIVE_NOT_RECRUITING

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

Conditions

Myelofibrosis Myeloproliferative neoplasms Polycythemia Thrombocythemia Primary myelofibrosis Janus Kinase-Inhibitor

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-04-12

Study Completion:2028-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04576156

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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; * 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	* 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

Inclusion Criteria

Exclusion 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;
* 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

* 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

Contacts and Locations

Principal Investigator

Faye Feller

STUDY_DIRECTOR

Geron Corporation

Study Locations (Sites)

University of California-San Diego/Moores UCSD Cancer Center

La Jolla, California, 92093-1503

United States

UCLA David Geffen School of Medicine

Los Angeles, California, 90096

United States

Smilow Cancer Center at YNHH

New Haven, Connecticut, 06511

United States

BRCR Medical Center Inc

Plantation, Florida, 33326

United States

University of South Florida

Tampa, Florida, 33612

United States

Norton Cancer Institute

Louisville, Kentucky, 40207

United States

Ochsner Clinic Foundation

New Orleans, Louisiana, 70124

United States

Maryland Oncology Hematology

Rockville, Maryland, 20850

United States

Icahn School of Medicine at Mount Sinai

New York, New York, 10029

United States

Duke University Medical Center

Durham, North Carolina, 27710

United States

Gabrail Cancer Center

Canton, Ohio, 44718

United States

Prairie Lakes Health Care System, Inc.

Watertown, South Dakota, 57201

United States

Oncology Consultants

Houston, Texas, 77024

United States

The University of Texas MD

Houston, Texas, 77030-4000

United States

Community Cancer Trials of Utah

Ogden, Utah, 84405

United States

Utah Cancer Specialists

Salt Lake City, Utah, 84106

United States

Hematology Oncology Associates of Fredericksburg

Fredericksburg, Virginia, 22408

United States

Northwest Medical Specialties PLLC

Seattle, Washington, 98405

United States

Collaborators and Investigators

Sponsor: Geron Corporation

Faye Feller, STUDY_DIRECTOR, Geron Corporation

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-04-12

Study Completion Date2028-06-30

Study Record Updates

Study Start Date2021-04-12

Study Completion Date2028-06-30

Terms related to this study

Keywords Provided by Researchers

Myeloproliferative neoplasms
Polycythemia
Thrombocythemia
Primary myelofibrosis
Janus Kinase-Inhibitor

Additional Relevant MeSH Terms

Myelofibrosis