Pegylated Interferon Alfa-2a for the Treatment of Primary and Secondary Myelofibrosis following an Allogeneic Hematopoietic Cell Transplantation, The ATIOM Trial

Inclusion Criteria

• PRE-TRANSPLANT INCLUSION CRITERIA (STEP 1): Male or female subject aged >= 18 years
• PRE-TRANSPLANT INCLUSION CRITERIA (STEP 1): Diagnosis of primary or secondary myelofibrosis
• PRE-TRANSPLANT INCLUSION CRITERIA (STEP 1): Eligible to undergo a myeloablative or reduced intensity conditioning regimen (myeloablative conditioning [MAC] or reduced-intensity conditioning [RIC])
• PRE-TRANSPLANT INCLUSION CRITERIA (STEP 1): Eligible to undergo a standard of care bone marrow biopsy with aspirate as part of his or her routine pre-transplant work-up
• PRE-TRANSPLANT INCLUSION CRITERIA (STEP 1): Peripheral blood stem cell (PBSC) graft
• PRE-TRANSPLANT INCLUSION CRITERIA (STEP 1): 10/10 human leukocyte antigens (HLA) matched related or matched unrelated donor
• PRE-TRANSPLANT INCLUSION CRITERIA (STEP 1): Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• PRE-TRANSPLANT INCLUSION CRITERIA (STEP 1): For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women < 50 years of age: ** Amenorrheic for >= 12 months following cessation of exogenous hormonal treatments; and ** Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or ** Underwent surgical sterilization (bilateral oophorectomy or hysterectomy) * Women >= 50 years of age: ** Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or ** Had radiation-induced menopause with last menses >1 year ago; or ** Had chemotherapy-induced menopause with last menses >1 year ago; or ** Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy)
• PRE-TRANSPLANT INCLUSION CRITERIA (STEP 1): Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception
• TREATMENT INCLUSION CRITERIA (STEP 2): Male or female subject aged >=18 years
• TREATMENT INCLUSION CRITERIA (STEP 2): Diagnosis of primary or secondary myelofibrosis
• TREATMENT INCLUSION CRITERIA (STEP 2): Have undergone a myeloablative or reduced-intensity conditioning regimen (MAC or RIC) and be 50-80 days from day 0 of transplant at initiation of study therapy
• TREATMENT INCLUSION CRITERIA (STEP 2): Peripheral blood stem cell (PBSC) graft
• TREATMENT INCLUSION CRITERIA (STEP 2): 10/10 HLA matched related or matched unrelated donor
• TREATMENT INCLUSION CRITERIA (STEP 2): ECOG Performance Status =< 2
• TREATMENT INCLUSION CRITERIA (STEP 2): Total Bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• TREATMENT INCLUSION CRITERIA (STEP 2): Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional ULN
• TREATMENT INCLUSION CRITERIA (STEP 2): Estimated creatinine clearance >= 30 mL/min by Cockcroft-Gault formula
• TREATMENT INCLUSION CRITERIA (STEP 2): Thyroid stimulating hormone (TSH) and T4 within normal limits or adequately controlled thyroid function
• TREATMENT INCLUSION CRITERIA (STEP 2): For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women < 50 years of age: ** Amenorrheic for >= 12 months following cessation of exogenous hormonal treatments; and ** Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or ** Underwent surgical sterilization (bilateral oophorectomy or hysterectomy) * Women >= 50 years of age: ** Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or ** Had radiation-induced menopause with last menses >1 year ago; or ** Had chemotherapy-induced menopause with last menses >1 year ago; or ** Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy)
• TREATMENT INCLUSION CRITERIA (STEP 2): Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception
• TREATMENT INCLUSION CRITERIA (STEP 2): Male subjects must agree to use a condom during intercourse for the duration of study therapy
• TREATMENT INCLUSION CRITERIA (STEP 2): Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 from toxicities related to any prior cancer therapy, unless considered clinically not significant by the treating investigator
• TREATMENT INCLUSION CRITERIA (STEP 2): Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

Exclusion Criteria

• EXCLUSION CRITERIA (STEP 2): Receiving other investigational agents concurrently
• EXCLUSION CRITERIA (STEP 2): Prior systemic anti-cancer therapy or any investigational therapy within five half-lives prior to starting study treatment
• EXCLUSION CRITERIA (STEP 2): Prior radiotherapy within 6 weeks prior to the first dose of study treatment
• EXCLUSION CRITERIA (STEP 2): Major surgery within 6 weeks prior to starting study drug or patients who have not fully recovered from major surgery
• EXCLUSION CRITERIA (STEP 2): The diagnosis of another malignancy within =< 2 years before study enrollment, except for those considered to be adequately treated with no evidence of disease or symptoms and/or will not require therapy during the study duration (i.e., basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix, or low-grade prostate cancer with Gleason score =< 6)
• EXCLUSION CRITERIA (STEP 2): Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions: * Graft-versus-host disease: ** Acute or chronic * Cardiovascular disorders: ** Congestive heart failure New York Heart Association class III or IV, unstable angina pectoris, serious cardiac arrhythmias ** Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 3 months before the first dose ** Corrected QT interval (QTc) prolongation defined as a corrected QT interval by Fredericia (QTcF) > 500 ms ** Known congenital long QT ** Left ventricular ejection fraction < 55% ** Uncontrolled hypertension defined as >= 140/90 as assessed from the mean of three consecutive blood pressure measurements taken over 10 minutes * Any other condition that would, in the Investigator’s judgment, contraindicate the subject’s participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, [subjects may not receive the drug through a feeding tube], social/ psychological issues, etc.)
• EXCLUSION CRITERIA (STEP 2): Active infection including human immunodeficiency virus (HIV), tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and tuberculosis (TB) testing in line with local practice) or hepatitis C. * Note: Subjects with a past or resolved hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of hepatitis B virus surface antigen [HBsAg]) are eligible
• EXCLUSION CRITERIA (STEP 2): Autoimmune hepatitis or decompensated hepatic disease
• EXCLUSION CRITERIA (STEP 2): Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study
• EXCLUSION CRITERIA (STEP 2): Known prior severe hypersensitivity to investigational product (IP) or any component in its formulations (National Cancer Institute [NCI] CTCAE v5.0 grade >= 3)
• EXCLUSION CRITERIA (STEP 2): Subjects taking prohibited medications. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment
• EXCLUSION CRITERIA (STEP 2): History of neuropsychiatric disease, autoimmune disease, or pancreatitis
• EXCLUSION CRITERIA (STEP 2): Presence of active interstitial lung disease or pneumonitis, bronchiolitis obliterans, pulmonary hypertension, ulcerative and hemorrhagic/ischemic colitis, and ophthalmologic disorders