Bomedemstat (IMG-7289) Plus Ruxolitinib for Myelofibrosis

Myelofibrosis Clinical Trial

Official title:

Phase 2 Study to Assess the Safety and Efficacy of Bomedemstat (IMG-7289) in Combination With Ruxolitinib in Patients With Myelofibrosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05569538
• Other study ID #: IMG-7289-IIS001
• Status: Recruiting
• Phase: Phase 2
• Start date: December 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2022
• Source: The University of Hong Kong
• Contact: Harinder Gill, MD
• Phone: +852 22554542
• Email: gillhsh[@]hku.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, Phase 2 study of bomedemstat (IMG-7289), an inhibitor of lysine-specific demethylase 1 (LSD1), in combination with JAK inhibition (JAKi) in patients with myelofibrosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Cohort A:

1. Patients refractory to, relapsed or intolerant of ruxolitinib as per one of the below:

• Refractory is defined as <30% reduction in spleen length or <10% SVR compared to baseline having received ruxolitinib for =12 weeks prior to enrollment, AND on a stable dose for =8 weeks prior to starting investigational therapy

• Relapsed is defined as an increase in spleen volume of =25% by MRI/CT from nadir, or, =100% in palpable spleen length from a baseline of 5 to 10 cm BLCM or, =50% increase in spleen length from a baseline spleen length =10 cm BLCM

• Intolerance is defined as the development in patients treated with ruxolitinib for =28 days of:

• Red blood cell transfusion requirement of 2 units/month for 2 months

• Grade 3 thrombocytopenia, anemia, hematoma, and/or hemorrhage while on ruxolitinib treatment

Cohort B:

1. Patients who are JAK inhibitor naïve, AND:

• Require MF-directed treatment, AND

• Have measurable disease burden including one of the following:

• Disease-related symptoms, determined by a MFSAF or MPN-SAF TSS of =10, or at least 2 symptoms with scores =3

• Documented splenomegaly by physical exam, with spleen palpated =5 cm below the left costal margin

Both Cohorts A and B:

2. Willing and able to provide informed consent

3. Age =18 years

4. Diagnosis of Overt Myelofibrosis (primary, post-ET, or post-PV) per World Health Organization (WHO) diagnostic criteria

5. Intermediate-1, Intermediate-2, or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS)

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

7. Platelet count =100 x 10^9/L prior to dosing on Cycle 1 Day 1

8. Absolute neutrophil count =0.5 x 10^9/L prior to dosing on Cycle 1 Day 1

9. Peripheral blast count =10% prior to dosing on Cycle 1 Day 1

10. Able to swallow capsules

11. Women of childbearing potential and fertile men must agree to use an approved method of contraception from Screening until 30 days after the last dose of bomedemstat and ruxolitinib.

Exclusion Criteria:

1. Those with increased risk of bleeding, including any of the following:

1. Activated partial thromboplastin time (aPTT) =1.3 x the local upper limit of normal

2. International normalized ratio (INR) =1.3 x the local upper limit of normal

3. Known history of a platelet function disorder

4. Other known bleeding disorder that is active at the time of screening (Von Willebrand's disease, dysfibrinogenemia, hemophilia, etc.)

2. History of splenectomy or prior splenic irradiation

3. Use of an investigational agent within 14 days of study treatment (or at least 7 half-lives of that agent, whichever is longer), prior to the first dose of bomedemstat

4. Current use of monoamine oxidase A and B inhibitors (MAOIs)

5. Uncontrolled, active infection

6. Major surgery within 4 weeks of starting the study drug, or not recovered from side effects of surgery

7. Any other serious medical conditions that could compromise study participation, in the opinion of the investigator

8. Known HIV infection or known, active hepatitis B or hepatitis C infection

9. Concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, i.e., non-melanoma skin cancers, are eligible)

10. Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment

11. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to bomedemstat or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that contraindicates participation

12. Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to hemolysis) as defined by any of the following local lab parameters:

1. Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) <40 mL/min or serum creatinine >1.5 x the local upper limit of normal

2. Aspartate transaminase (AST) or alanine aminotransferase (ALT) =2.5 x the local upper limit of normal

13. Pregnant or lactating females, or females planning to become pregnant at any time during the study

14. Unwilling or unable to comply with the study protocol

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• Bomedemstat
Bomedemstat will be self-administered orally once daily. In both cohorts, the dose of bomedemstat will be adjusted in each patient based on titration of the patient's platelet count to the target range. Ruxolitinib will be self-administered orally. Both medications will continue uninterrupted in 28-day cycles. Subjects will continue combination treatment through the Initial Treatment Period (first 6 cycles), which includes a Qualification Assessment. Those deriving clinical benefit in the opinion of the treating physician may continue receiving combination treatment in the Additional Treatment Period (6 cycles). Qualification Assessments will be performed at the end of each Additional Treatment Period, which is iterative, and may repeat for as long as clinical benefit is sustained, at the discretion of the treating physician.

Locations

Country	Name	City	State
Hong Kong	Department of Medicine, the University of Hong Kong, Queen Mary Hospital	Hong Kong

Sponsors (2)

Lead Sponsor	Collaborator
The University of Hong Kong	Imago BioSciences,Inc.

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Enumeration and description of adverse events (AEs), including determination of dose limiting toxicities (DLTs), serious adverse events (SAEs), and other AEs	24 months
Secondary	Spleen response at 24 weeks	Proportion of patients who experience a spleen length reduction by palpation of =30% OR spleen volume reduction (SVR) of =35% by MRI or CT by 24 weeks of treatment	24 weeks
Secondary	Symptom response at 24 weeks	Proportion of patients who describe a =50% reduction in symptom burden by the Myelofibrosis Symptom Assessment Form (MFSAF) by 24 weeks of treatment	24 weeks