NCT01291784终止1 期
Phase I Study of GC1008 in Patients With Primary Myelofibrosis (PMF), Post-polycythemia Vera/Essential Thrombocythemia Related Myelofibrosis (Post-PV/ET MF)
适应症
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Safety and Tolerability
研究概览
简要总结
TGF-β is a cytokine that is found to be upregulated in the bone marrow of patients with myelofibrosis. This cytokine likely plays a dual role in promoting myelofibrosis and myeloproliferation, both of which are the bone marrow morphologic hallmark of MF. The investigators propose that inhibiting the TGF-β signaling pathway in MF will decrease the fibrogenic stimuli leading to myelofibrosis and concomitantly interrupt myeloproliferation. This is a novel approach to the treatment of patients with myelofibrosis.
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
- •Intermediate-1 or higher by IWG-MRT Post PV/ET MF patients OR intermediate-1 or higher JAK2V617F negative PMF
- •Bone marrow MF-2 or higher as assessed by the European consensus grading score AND grade 3 or higher by modified Bauermeister scale.
- •Patients must be able to give written informed consent to participate. Patients may not be consented by a durable power of attorney.
- •Male and female patients of child-producing potential must agree to use effective contraception while enrolled on study and receiving the investigational agent, and for at least 3 months after the last treatment.
- •At the time of enrollment, patients must be >4 weeks since major surgery, radiotherapy, chemotherapy (except hydroxyurea) immunotherapy, or biotherapy/targeted therapies and recovered from the toxicity of prior treatment to < Grade 1, exclusive of alopecia. Concurrent cancer therapy is not permitted for the exception of hydroxyurea if already being used at a stable dose for 3 weeks prior to screening.
- •Patients must have negative tests for human immunodeficiency virus (HIV) and for hepatitis viruses B and C (antibody and/or antigen) unless the result is consistent with prior vaccination or prior infection with full recovery.
- •Marrow: Absolute neutrophil count ≥ 500/mm3, and platelet count ≥50,000/mm3 without the need for platelet transfusion within 4 weeks
- •Hepatic: Serum total bilirubin >1.5 X upper limit of normal (ULN) (Patients with Gilbert's Disease may be included if their total bilirubin is >3.0 mg/dL); alanine aminotransferase (ALT), and aspartate aminotransferase (AST) >2.5 X ULN.
- •Renal: Serum creatinine of < 1.5 x upper limit of normal (ULN) or, if higher, estimated or measured creatinine clearance >45 mL/min.
- •Coagulation:
- •Prothrombin Time (PT) < 1.5 X ULN
- •Partial thromboplastin time (aPTT) < 1.5 X ULN
排除标准
- •Central nervous system (CNS) cancer or metastases, meningeal carcinomatosis, malignant seizures, or a disease that either causes or threatens neurologic compromise (e.g., unstable vertebral metastases).
- •Pregnant or nursing women, due to the unknown effects of GC1008 on the developing fetus or newborn infant.
- •Patients with known bleeding diathesis or signs of uncontrolled active bleeding (hematuria, GI bleeding) other than self-limited causes of benign etiology that have been adequately investigated at the discretion of the investigator.
- •Patients requiring anticoagulation with aspirin > 81mg daily, unfractionated heparin, low molecular weight heparin (LMWH), direct anti-thrombin inhibitors, or vitamin K antagonists (e.g. warfarin). This does not apply to patients actively receiving aspirin at a dose of ≤ 81mg a day.
- •Patients diagnosed with another malignancy - unless following curative intent therapy, the patient has been disease free for at least 5 years and the probability of recurrence of the prior malignancy is >5%. Patients with curatively treated early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia (CIN) are eligible for this study.
- •Patients with an organ transplant, including those that have received an allogeneic bone marrow transplant.
- •Use of investigational agents within 4 weeks prior to study enrollment (within 6 weeks if the treatment was with a long-acting agent such as a monoclonal antibody).
- •Significant or uncontrolled medical illness, such as congestive heart failure (CHF), myocardial infarction, symptomatic coronary artery disease, significant ventricular arrhythmias within the last 6 months, or significant pulmonary dysfunction. Patients with a remote history of asthma or active mild asthma may participate.
- •Active autoimmune disorders or concurrent immunosuppressive medications such as prednisone, interferon, cyclosporine, methotrexate or azathioprine.
- •Active infection requiring antibiotics.
- •A known allergy to any component of GC
- •Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems that warrant exclusion. Examples of significant problems include, but are not limited to:
- •Other serious non-malignancy-associated medical conditions that may be expected to limit life expectancy or significantly increase the risk of SAEs.
- •Any condition, psychiatric, substance abuse, or otherwise, that, in the opinion of the Investigator, would preclude informed consent, consistent follow-up, or compliance with any aspect of the study
结局指标
主要结局
Safety and Tolerability
时间窗: 28 days
To assess the safety and tolerability of GC1008 in patients with primary myelofibrosis (PMF) or post-polycythemia vera/essential thrombocythemia myelofibrosis (Post-PV/ET MF). A total of 9 AEs determined by the investigator to be at least possibly related to GC1008 occurred during the study.
次要结局
- Bauermeister Scale(6 months)
- JAK2V617F Allele Burden(6 months)
- European Consensus Fibrosis Grade(6 months)
- Peripheral Blood CD34+(6 months)
研究者
John Mascarenhas
Principal Investigator
Icahn School of Medicine at Mount Sinai
研究点 (1)
Loading locations...
相似试验
已完成
1 期
MPN-RC 118 AVID200 in MyelofibrosisPost-essential Thrombocythemia MyelofibrosisPost-polycythemia Vera MyelofibrosisPost ET MFPost PV MFPrimary MyelofibrosisNCT03895112John Mascarenhas21
已完成
不适用
Growth Factor Levels in the Blood of Patients Undergoing Radiation Therapy for Epithelial CancerHead and Neck CancerBreast CancerProstate CancerColorectal CancerLung CancerNCT00897793Vanderbilt-Ingram Cancer Center25
已完成
不适用
Investigation of biomarkers for assessment of fatigue and stress-associated childhood illnesses.fatigue and stress-associated childhood illnessesJPRN-UMIN000012192Department of Virology, The Jikei University School of Medicine31
尚未招募
2 期
OT-101 in Combination With Pembrolizumab in Subjects With Malignant Pleural Mesothelioma Failing to Respond to Checkpoint InhibitionMalignant Pleural MesotheliomaNCT05425576Oncotelic Inc.63
Unknown
不适用
Assessment of the TGF-beta Pathway and Micro-RNA in Pediatric Pulmonary Arterial HypertensionPulmonary Arterial HypertensionNCT04489251Medical College of Wisconsin40