A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Imetelstat in Combination With Ruxolitinib in Participants With Myelofibrosis

Geron

Status and phase: Enrolling; Phase 1

Conditions: Myelofibrosis

Treatments: Drug: Imetelstat sodium; Drug: Ruxolitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05371964

MYF1001

Details and patient eligibility

About

The purpose of the study is to identify the recommended Part 2 dose (R2PD) of imetelstat sodium in combination with ruxolitinib in participants with myelofibrosis (MF) in Part 1, and to evaluate the safety and preliminary clinical activity of the R2PD of imetelstat sodium in combination with ruxolitinib in participants with MF in Part 2.

Enrollment: 36 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of primary myelofibrosis (PMF) according to the revised World Health Organization (WHO) criteria or post-essential thrombocythemia-MF or post-polycythemia vera according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria.

• Dynamic International Prognostic Scoring System (DIPSS) intermediate-1, intermediate-2 or high-risk MF.

• Candidate for ruxolitinib treatment:

  • Part 1 participants: On ruxolitinib treatment for at least 12 weeks with at least 4 consecutive weeks immediately prior to enrollment at a stable dose.
  • Part 2 participants: Candidate for ruxolitinib treatment as assessed by the investigator and has not previously been treated with a JAK inhibitor (Cohort A) OR currently receiving ruxolitinib per standard of care for at least 12 weeks with at least 4 consecutive weeks at a stable dose prior to enrollment (Cohort B). Note that the study will no longer recruit participants into Cohort A.

• Active symptoms of MF on the MFSAF v4.0 demonstrated by:

  • Part 1 participants only: At least 2 symptoms with a score ≥ 1
  • Part 2 participants only: At least 2 symptoms with a score of ≥ 3, or a total score of at least 10.

• Ineligible for or unwilling to undergo hematopoietic stem cell transplant at time of study entry.

• Hematology laboratory test values within protocol defined limits.

• Biochemical laboratory test values 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%.

• Prior treatment with JAK inhibitor (except for participants being dosed optimized on ruxolitinib treatment prior to screening and enrollment in part 1 or Part 2 Cohort B).

• Known allergies, hypersensitivity, or intolerance to imetelstat or ruxolitinib or excipients.

• Prior treatment with imetelstat.

• Major surgery within 28 days prior to enrollment.

• Any investigational drug regardless of class or mechanism of action, hydroxyurea, chemotherapy, (except for ruxolitinib for participants being dose optimized prior to enrollment), immunomodulatory or immunosuppressive therapy, corticosteroids >30 mg/day prednisone or equivalent ≤14 days prior to enrollment.

• Prior history of hematopoietic stem cell transplant.

• 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 enrollment.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Adequately treated cervical carcinoma in situ without evidence of disease.

• Clinically significant cardiovascular disease.

• Known history of human immunodeficiency virus (HIV) or any uncontrolled active systemic infection requiring IV antibiotics.

• Active systemic hepatitis infection requiring treatment or any known acute or chronic liver disease unless related to MF. Carriers of hepatitis virus are permitted to enter the study.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

---

36 participants in 2 patient groups

Part 1: Imetelstat sodium + Ruxolitinib

Experimental group

Description:

Participants who have received ruxolitinib orally (PO) as part of standard of care (SOC) for at least 12 weeks prior to Screening will be enrolled. After enrollment, participants will initiate imetelstat sodium therapy. Dose levels of imetelstat sodium may include 4.7, 6, 7.5, 9.4 mg/kg, until a RP2D is established.

Treatment:

Drug: Ruxolitinib

Drug: Imetelstat sodium

Part 2: Imetelstat sodium + Ruxolitinib

Experimental group

Description:

Cohort A: Janus Kinase (JAK) inhibitor naive participants will receive initial treatment with ruxolitinib on study for at least 12 weeks, including 4 consecutive weeks at a stable dose, prior to the addition of imetelstat sodium. Participants can begin imetelstat sodium treatment after sponsor review and approval and meet the following requirements: platelet value is ≥75 x 10\^9/L for two consecutive measurements, at least 1 week apart, and the participant does not meet criteria for dose delay. Note that the study will no longer recruit participants into Cohort A. Cohort B: Participants will receive treatment with ruxolitinib for 12 weeks with at least 4 consecutive weeks at a stable dose prior to enrollment and will start combination treatment with imetelstat on study.

Treatment:

Drug: Ruxolitinib

Drug: Imetelstat sodium