Canakinumab treatment for patients with myelofibrosis

A Phase 2 Study of Canakinumab in Patients With Myelofibrosis Myeloproliferative Neoplasms Research Consortium [MPN-RC 122]

This study is testing if Canakinumab can safely help people with myelofibrosis feel better when given through injections every three weeks.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Icahn School of Medicine at Mount Sinai (Academic / other)
• Drugs / interventions: Canakinumab, ruxolitinib, fedratinib, prednisone
• Locations: 8 sites (Phoenix, Arizona and 7 other locations)
• Trial ID: NCT05467800 on ClinicalTrials.gov

What this trial studies

This is an open-label, multicenter phase 2 trial evaluating the efficacy and safety of Canakinumab in patients diagnosed with primary myelofibrosis or post-essential thrombocythemia/polycythemia vera related myelofibrosis. Eligible participants will receive Canakinumab via subcutaneous injection every three weeks for a total of eight cycles. The study will assess treatment responses and monitor for any unacceptable toxicities, with an interim analysis planned after the enrollment of 10 patients. The trial aims to determine if the treatment is effective and safe for this patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a confirmed diagnosis of primary myelofibrosis or post-essential thrombocythemia/polycythemia vera related myelofibrosis and specific hemoglobin criteria.

Not a fit: Patients who do not meet the inclusion criteria or have other significant health issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from myelofibrosis.

How similar studies have performed: While this approach is being tested in this specific context, similar studies have shown promise in targeting myelofibrosis with novel therapies.

Eligibility criteria

INCLUSION CRITERIA:

The following are required for inclusion in the study:

* Patients must voluntarily sign informed consent form (ICF) and be willing and able to adhere to the study visit schedule and all protocol requirements.
* Patients must be ≥ 18 years of age at the time of signing the ICF.
* Patients must have a pathologically confirmed diagnosis of primary myelofibrosis (PMF) as per the World Health Organization (WHO) diagnostic criteria44 or post-essential thrombocythemia (ET) / post-polycythemia vera (PV) MF according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria.45
* Patients must have at least one of the following:

  * Hemoglobin \< 10 g/dL;
  * Transfusion-dependency (at least 6 units of packed red blood cells (PRBC) in the 12 weeks prior to study enrollment, for a hemoglobin \< 8.5 g/dL, in the absence of bleeding or treatment-induced anemia with the most recent transfusion having occurred in the 28 days prior to study enrollment;
  * Splenomegaly palpated ≥ 5 cm below the left costal margin (LCM);
  * MF-SAF version 4.0 score ≥ 10.
* A bone marrow biopsy must be performed within the 30-day screening period; however, a bone marrow biopsy obtained within 90 days of screening without intervening treatments and approved by the study chair may suffice.
* Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
* Life expectancy of at least 6 months.
* At least two weeks must have elapsed between the last dose of any MF-directed drug treatments (including investigational therapies and excluding hydroxyurea) and study enrollment.
* Not eligible for ruxolitinib/fedratinib therapy due to a platelet count of \< 50 x 109/L or previously treated and lack/loss of response per investigator discretion.
* Recovery to ≤ grade 1 or baseline of any toxicities due to prior systemic treatments excluding alopecia.
* Women of childbearing potential (WCBP) must have a negative urine or serum pregnancy test within 28 days of starting the study drug. Men and women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence, tubal ligation, vasectomy) prior to cycle 1 day 1 and for 130 days after stopping study treatment. Vasectomy must be performed a minimum of 3 months before study start.
* Must have adequate organ function as demonstrated by the following:

  * ALT/AST ≤ 3.0X ULN, or ≤ 4X ULN (unless if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis (EMH) related to MF);
  * Direct bilirubin ≤ 1.5 x ULN or ≤ 2.0 x ULN (unless if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis related to MF or documented Gilbert's syndrome);
  * Serum creatinine ≤ 2.0 mg/dL;
  * Platelet count ≥ 25 x 109/L (patient must not have had platelet transfusion in the 14 days prior to screening platelet count);
  * ANC ≥ 1000/μL.
* Patient must be willing to receive red blood cell and/or platelet transfusions if indicated.

EXCLUSION CRITERIA:

Any of the following is a criterion for exclusion from the study:

* Prior malignancy active within the previous ≤1 year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
* Any of the following cardiac abnormalities

  * Uncontrolled, symptomatic congestive heart failure as designated by the treating physician;
  * Myocardial infarction ≤ 6 months prior to enrollment;
  * Unstable angina pectoris designated by treating physician;
  * Serious uncontrolled cardiac arrhythmia as designated by treating physician;
  * Uncontrolled hypertension as designated by treating physician.
* Known history of human immunodeficiency virus (HIV) (no laboratory testing is required), or active infection with hepatitis B or Hepatitis C.
* Active tuberculosis (Tb) infection or documented, untreated latent Tb infection (all patients should undergo Tb risk evaluation prior to enrollment with Tb screening performed as per local guidelines.)
* Active, uncontrolled infection at the time of enrollment, except in cases of localized infections that are unlikely to lead to a systemic infection such as onychomycoses or dental caries
* Patients with a new fever (T\>38.0o C) or respiratory symptoms are required to undergo laboratory screening for COVID-19.
* Have undergone prior allo-HSCT for treatment of any hematological disorder or prior solid organ transplant.
* Any serious or uncontrolled psychiatric or medical disorder that, in the opinion of the investigator, may increase the risk associated with the study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
* Women who are pregnant or breastfeeding.
* Patients undergoing concurrent treatment with agents targeting tumor necrosis factor alpha (TNFα) or IL-1 within 28 days of study enrollment.
* Patients who have received a live vaccination within 30 days before study drug administration (patients should not be treated with live-virus vaccine while undergoing therapy and 130 days after Canakinumab discontinuation).
* Patients with a condition requiring systemic treatment with corticosteroids within 14 days of study drug administration (i.e. prednisone at doses of \> 10 mg). Inhaled or topical steroids and adrenal/pituitary replacement doses ≤ 10mg daily of prednisone or equivalent are permitted.

Where this trial is running

Phoenix, Arizona and 7 other locations

• Mayo Clinic Arizona — Phoenix, Arizona, United States (Active_not_recruiting)
• Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute — Los Angeles, California, United States (Active_not_recruiting)
• Moffitt Cancer Center — Tampa, Florida, United States (Active_not_recruiting)
• The University of Kansas Cancer Center-Westwood — Westwood, Kansas, United States (Recruiting)
• Ruttenberg Treatment Center — New York, New York, United States (Recruiting)
• Atrium Health Levine Cancer Institute — Charlotte, North Carolina, United States (Not_yet_recruiting)
• Wake Forest Baptist Health Comprehensive Cancer Center — Winston-Salem, North Carolina, United States (Recruiting)
• Cleveland Clinic Foundation — Cleveland, Ohio, United States (Active_not_recruiting)

Study contacts

• Study coordinator: Ashley Yu

Conditions Primary Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; ET-MF; Post-polycythemia Vera Related Myelofibrosis; PV-MF