Ruxolitinib Pre-, During- and Post-HSCT for Patients With Primary or Secondary Myelofibrosis.

Korábbi kezelés

• Prior history of progressive multifocal leukoencephalopathy (PML)
• Concomitant receipt of St. John's Wort
• Prior allogeneic transplant for any hematopoietic disorder
• Had accelerated phase or leukemic transformation (≥10% blasts in PB or BM any time prior to HCT)
• Not able to take oral medication

Más betegség

• Hypersensitivity to any JAK inhibitor, including ruxolitinib, fedratinib, or any other JAK inhibitor
• Patients with uncontrolled infection (patients with stable controlled infections such as hepatitis B or HIV patients with undetectable viral load on antiviral treatment would be eligible). Patients who are actively ill and require hospitalization to treat an infection will be excluded.
• History of another malignancy within 5-years of date of enrollment except those who have received definitive treatment. Definitive treatment will be defined as the use of surgery, chemotherapy or radiation for the treatment of a malignancy, which susbsquently has no evidence of disease after 2 years or \<10% probably of recurrence after 1 year. In addition, patients with history of the following are eligible:
  • basal cell or squamous cell carcinoma of skin
  • Polycythemia Vera or Essential Thrombocythemia
  • ductal carcinoma in situ (DCIS)
  • superficial bladder cancer
  • prostatic intraepithelial neoplasia (PIN)
• Have an uncontrolled intercurrent illness including, but not limited to, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Laborértékek

• Patients without normal organ function defined as follows:
  • AST (SGOT), ALT (SGPT) and Alkaline Phosphatase ≥ 3 × institutional Upper Limit of Normal (ULN)
  • Direct bilirubin \>2.0 mg/dL
  • Calculated creatinine clearance ≤60 mL/min (Cockcroft-Gault formula)
  • Note: patients with CrCl ≤60 mL/min but with normal creatinine (within institutional normal ranges) and no other evidence of inadequate renal function are eligible.
• Have current or a history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF \< 40%, as measured by MUGA scan or echocardiogram)

Egyéb

• Pregnancy at the time of enrollment
• Unable to give informed consent

• Participants must have pathologically confirmed primary myelofibrosis according to WHO criteria or secondary myelofibrosis as defined by the IWG-MRT criteria.
  • Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria (Appendix G) OR
  • Intermediate-1 risk disease with one of the following additional unfavorable features known to impact the survival adversely
  • Red cell transfusion dependency
  • Unfavorable Karyotype
  • Platelet count ≤100 x 10\^9/L
  • Presence of a high risk molecular marker associated with worsened overall survival (ASXL1, EZH2, IDH1/2, SRSF2, U2AF1, p53)
• Age 18-75
• Participants must be designated to undergo reduced intensity allogeneic peripheral blood (PB) or bone marrow (BM) hematopoietic stem cell transplantation. Consent will be obtained prior to admission for HCT.
• Participants who will undergo HCT from the following donor types are eligible:
  • 6/6 (HLA-A, B, DR) fully matched related donor
  • 8/8 (HLA-A, B, DR, C) fully matched unrelated donor. Matching in the unrelated setting must be at the allele level
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Life expectancy of greater than 3 months
• Able to give informed consent
• Off all MF-directed therapy at the time of enrollment, with the exception of ruxolitinib, one week or 4 half-lives (effective), whichever is longer, prior to the first dose of study treatment
• No allergy to ruxolitinib in the past
• For patients already receiving ruxolitinib at the time of enrollment, patients should be treated with ruxolitinib for a sufficient time to optimize spleen response or symptoms, at the discretion of the treating provider, prior to enrollment. Patients who have had prior splenectomy are eligible.