allogeneic hematopoietic cell transplantation with pegylated interferon alfa-2a for primary and secondary myelofibrosis

Conditions: Myelofibrosis

Summary: this is a single site, open-label, dose de-escalation, phase 1 study of pegylated interferon alfa-2a administered after allohct in subjects with primary or secondary myelofibrosis. part 1 of the study will assess the rate of dose-limiting toxicities (dlts) during the dlt evaluation period and identify the recommended phase 2 dose (rp2d). once the rp2d is identified, 6 additional patients will be enrolled in the expansion cohort.


Eligibility criteria:
inclusion criteria: pre-transplant inclusion criteria (step 1) * male or female subject aged ≥ 18 years. * diagnosis of primary or secondary myelofibrosis. * eligible to undergo a myeloablative or reduced intensity conditioning regimen (mac or ric) * eligible to undergo a standard of care bone marrow biopsy with aspirate as part of his or her routine pre-transplant work-up. * peripheral blood stem cell (pbsc) graft * 10/10 hla matched related or matched unrelated donor * ecog performance status ≤ 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). * 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 as described in section 5.4.1. treatment inclusion criteria (step 2) * male or female subject aged ≥ 18 years. * diagnosis of primary or secondary myelofibrosis. * 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. * peripheral blood stem cell (pbsc) graft * 10/10 hla matched related or matched unrelated donor * ecog performance status ≤ 2. * adequate organ function as defined as: * hepatic: * total bilirubin ≤ 1.5x institutional upper limit of normal (uln) * ast(sgot)/alt(sgpt) ≤ 3 × institutional uln * renal: * estimated creatinine clearance ≥ 30 ml/min by cockcroft-gault formula: * tsh and t4 within normal limits or adequately controlled thyroid function. * 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). * 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 as described in section 5.4.1. * male subjects must agree to use a condom during intercourse for the duration of study therapy as described in section 5.4.1. * recovery to baseline or ≤ grade 1 ctcae v5.0 from toxicities related to any prior cancer therapy, unless considered clinically not significant by the treating investigator. * 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 * prior systemic anti-cancer therapy or any investigational therapy within five half-lives prior to starting study treatment. * prior radiotherapy within 6 weeks prior to the first dose of study treatment. * major surgery within 6 weeks prior to starting study drug or patients who have not fully recovered from major surgery. * 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). * 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 (eg, deep venous thrombosis, pulmonary embolism) within 3 months before the first dose. * qtc prolongation defined as a 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.) * active infection including hiv, tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and tb testing in line with local practice) or hepatitis c. * note: subjects with a past or resolved hbv infection (defined as the presence of hepatitis b core antibody \[anti-hbc\] and absence of hbsag) are eligible. * autoimmune hepatitis or decompensated hepatic disease * 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. * known prior severe hypersensitivity to investigational product (ip) or any component in its formulations (nci ctcae v5.0 grade ≥ 3). * subjects taking prohibited medications as described in section 6.5.1. 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. * history of neuropsychiatric disease, autoimmune disease, or pancreatitis. * presence of active interstitial lung disease or pneumonitis, bronchiolitis obliterans, pulmonary hypertension, ulcerative and hemorrhagic/ischemic colitis, and ophthalmologic disorders.