Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
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, previously treated and lack/loss of response as defined by at least one of the
following:
- Treatment for ≥ 3 months with inadequate efficacy response defined as < 10%
spleen volume reduction by MRI or <30% decrease from baseline in spleen length by
physical examination or regrowth to these parameters following an initial
response and/or;
- Treatment for ≥ 28 days complicated by either:
- Development of a red blood cell transfusion requirement (at least 2
units/month for two months) and/or;
- National Cancer Institute (NCI) CTCAE grade ≥ 3 AEs of thrombocytopenia,
anemia, hematoma, and/or hemorrhage while being treated with a dosage of <
20 mg BID.
- 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/?L.
- 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 2 years 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 (TNF?) 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.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 9/15/22. Questions regarding updates should be directed to the study team contact.