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

• Status: Recruiting
• Trial end date: 2024-05-01
• Target enrollment: 0
• Participant gender: All

Summary

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 refractory to Janus Kinase (JAK)-Inhibitor treatment.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Geron Corporation
• Treatments: Imetelstat; Motesanib diphosphate

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

• Refractory to JAK-inhibitor treatment as defined in either inclusion (i) or (ii):

(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 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 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])

• 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 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