NCT05535764招募中1 期
Allogeneic Hematopoietic Cell Transplantation With Pegylated Interferon Alfa-2a for Primary and Secondary Myelofibrosis (ATIOM)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Rate of dose-limiting toxicities (DLTs) during the DLT evaluation period
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≤
- •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.
- •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 ≤
- •Adequate organ function as defined as:
- •Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
- •AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
- •--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.
- •Male subjects must agree to use a condom during intercourse for the duration of study therapy as described in Section 5.4.
- •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.
排除标准
- •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.
- •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.
研究组 & 干预措施
Treatment: All Patients
Experimental
A 3+3 dose de-escalation design will be used to determine the recommended phase 2 dose,while ensuring the safety and tolerability of the treatment. In this trial, the dose determined to be the maximum tolerated dose will be the recommended phase 2 dose and will be utilized in the cohort expansion.
干预措施: Pegylated interferon alpha2a (Drug)
结局指标
主要结局
Rate of dose-limiting toxicities (DLTs) during the DLT evaluation period
时间窗: Start of treatment to 86 days after treatment initiation
To identify the Recommended Phase 2 Dose (RP2D) of pegylated interferon alfa-2a in subjects undergoing allogeneic hematopoietic cell transplantation for primary or secondary myelofibrosis
次要结局
- Assess leukemia-free survival (LFS) in the study population.(3 years)
- Assess the tolerability of pegylated interferon alfa-2a in the study population.(3 years)
- Assess the safety of pegylated interferon alfa-2a in the study population.(3 years)
- Assess the rate of treatment-related mortality in the study population.(3 years)
- Assess the incidence of acute and/or chronic graft versus host disease (GVHD) in the study population(3 years)
- Assess Objective Response Rate (ORR) in the study population.(3 Years)
研究者
研究点 (2)
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