Combining bomedemstat and ruxolitinib for treating myelofibrosis

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

This study is testing a new combination of two medications, bomedemstat and ruxolitinib, to see if it can help people with myelofibrosis who haven't responded to other treatments or are new to JAK inhibitors.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The University of Hong Kong (Academic / other)
• Drugs / interventions: ruxolitinib
• Locations: 1 site (Hong Kong)
• Trial ID: NCT05569538 on ClinicalTrials.gov

What this trial studies

This Phase 2 clinical trial evaluates the effectiveness of bomedemstat (IMG-7289), a lysine-specific demethylase 1 (LSD1) inhibitor, in combination with ruxolitinib, a JAK inhibitor, for patients with myelofibrosis. The study includes two cohorts: one for patients who have not responded to or cannot tolerate ruxolitinib, and another for those who are new to JAK inhibitors and require treatment for myelofibrosis. The trial aims to assess the safety and efficacy of this combination therapy in managing the disease.

Who should consider this trial

Good fit: Ideal candidates include patients with myelofibrosis who are either refractory to, relapsed from, or intolerant of ruxolitinib, as well as those who are JAK inhibitor naïve.

Not a fit: Patients who have not been diagnosed with myelofibrosis or those who have already exhausted all treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with myelofibrosis who have limited treatment choices.

How similar studies have performed: While this approach is innovative, similar studies combining JAK inhibitors with other therapies have shown promise, indicating potential for success.

Eligibility criteria

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

Where this trial is running

Hong Kong

• Department of Medicine, the University of Hong Kong, Queen Mary Hospital — Hong Kong, Hong Kong (Recruiting)

Study contacts

• Principal investigator: Harinder Gill, MD — Department of Medicine, the University of Hong Kong
• Study coordinator: Harinder Gill, MD

Conditions Myelofibrosis; Bomedemstat; Ruxolitinib