Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion

Description

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.

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) Refractory to Janus Kinase (JAK)-Inhibitor

Details

This is a multicenter study with 2 arms, and will include 3 phases: a) screening phase of up to 28 days before randomization during which participants will complete a 14-day washout period from all prior therapies including JAK-inhibitor treatment, and the participant's eligibility will be reviewed; b) treatment phase, from randomization until study treatment (imetelstat or BAT) discontinuation; and c) post treatment follow-up phase, that begins when the participant discontinues treatment, and will continue until death, lost to follow-up, withdrawal of consent, or study end, whichever occurs first. Participants will be randomized (2:1) into 2 Arms (Arm A will receive imetelstat and Arm B will receive BAT). Participants who meet progressive disease criteria and discontinue BAT, may crossover to receive imetelstat treatment after sponsor's approval.

Keywords

Myelofibrosis Myeloproliferative neoplasms Polycythemia Thrombocythemia Primary myelofibrosis Janus Kinase-Inhibitor Imetelstat Motesanib diphosphate Best Available Therapy (BAT)

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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) 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 cm3 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 CAN'T join 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 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

Locations

  • University of California-San Diego/Moores UCSD Cancer Center accepting new patients
    La Jolla California 92093-1503 United States
  • Prairie Lakes Health Care System, Inc. accepting new patients
    Watertown South Dakota 57201 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Geron Corporation
ID
NCT04576156
Phase
Phase 3
Study Type
Interventional
Last Updated