Allogeneic Hematopoietic Cell Transplantation With Pegylated Interferon Alfa-2a for Primary and Secondary Myelofibrosis (ATIOM)

Description

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.

Trial Eligibility

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.

Study Info

Interventions

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