NCT02282358终止1 期
An Open-Label Phase II Study of Mocetinostat in Selected Patients With Mutations of Acetyltransferase Genes in Relapsed and Refractory Diffuse Large B-Cell Lymphoma and Follicular Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Efficacy as Defined by Overall Response
研究概览
简要总结
The purpose of this study is to learn if the study drug mocetinostat can slow the progression of cancer in people who have a mutation in CREBBP or EP300 in the genetic makeup of their cancer. The potential side effects of mocetinostat will also be studied.
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
- •Patient has provided a signed study Informed Consent Form prior to performance of any study related procedurePatient is ≥ 18 years of age
- •Patient has histologically confirmed diagnosis of diffuse large B cell lymphoma or follicular lymphoma harboring mutations in CREBBP or EP300 with relapsed or refractory disease
- •Patients with diffuse large B cell lymphoma must have received at least two prior therapies and have received, declined or be ineligible for autologous or allogeneic stem cell transplant.
- •Patients with follicular lymphoma must have received at least two prior therapies.
- •Patients with either diffuse large B cell lymphoma or follicular lymphoma will be allowed to enroll after receiving only 1 prior therapy if they are felt to not be a candidate for further systemic chemotherapy.
- •Patient has at least one measurable lesion (≥ 2 cm) according to Cheson criteria [45]. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 - Patient has adequate bone marrow and organ function by:
- •Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
- •Platelets ≥ 75 x 10^9/L (no platelet transfusion within past 14 days)
- •Hemoglobin (Hgb) ≥ 9.0 g/dL (no RBC transfusion within past 14 days)
- •International Normalized Ratio (INR) ≤ 1.5
- •Serum Creatinine ≤ 1.5 x upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 2.5 x ULN, or ≤ 5.0 x ULN for patients with documented hepatic involvement
- •Serum bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN for patients with Gilbert Syndrome or documented hepatic involvement.
- •Patients must have fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy (residual grade 1 toxicity, e.g. grade 1 peripheral neuropathy, and residual alopecia are allowed)
排除标准
- •Patient has received previous treatment with HDAC inhibitors
- •Patient has evidence of graft versus host disease (GVHD)
- •Patient has active or history of central nervous system (CNS) disease
- •Patient has impaired cardiac function including any of the following:
- •Presence or history of pericardial effusion (definitions are provided in and/or pericarditis.
- •Acute myocardial infarction, symptomatic angina pectoris ≤ 6 months prior to starting study drug
- •Presence of congestive heart failure ≥ NYHA class 3
- •QTc > 480 ms on a screening ECG
- •Screening LVEF < 45% by echocardiography or MUGA
- •Uncontrolled cardiac arrhythmia including uncontrolled atrial fibrillation/atrial flutter/sinus tachycardia, complete left bundle branch block, congenital long QT syndrome
- •Presence of permanent cardiac pacemaker
- •Other clinically significant heart disease
- •Subject is taking warfarin at start of treatment or within 6 months prior to start of study treatment.
- •Patient has a concurrent malignancy or has a malignancy within 3 years of study enrollment (with the exception of adequately treated basal or squamous cell carcinoma or nonmelanomatous skin cancer)
- •Patient is concurrently using other approved or investigational antineoplastic agent
- •Patient has received chemotherapy, targeted anticancer therapy, pelvic and/or para-aortic radiotherapy or has had major surgery ≤ 4 weeks (6 weeks for nitrosourea, monoclonal antibodies or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy
- •Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of mocetinostat (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- •Patient is currently receiving increasing or chronic treatment (> 10 days) with corticosteroids or another immunosuppressive agent. The following uses of corticosteroids are permitted: single dose, topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
- •Patient has a history of non-compliance to medical regimen or inability to grant consent.
- •Concomitant medications causing prolonged QT which cannot be discontinued or changed to a different medication prior to initiating study
- •Patient is currently being treated with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. Patients must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the start of treatment.
- •Note: the oral anti-diabetic drugs troglitazone and pioglitazone are CYP3A inducers.
- •Patient has a known history of HIV (testing not mandatory), active Hepatitis B or C infection.
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum hCG laboratory test (> 5 mIU/mL)
- •Women of child bearing potential and men with reproductive potential, if they are unwilling to use adequate contraception while on study therapy and for 3 months thereafter
研究组 & 干预措施
Mocetinostat
Experimental
Patients who harbor mutations for CREBBP and/or EP300 will be started on mocetinostat 70 mg orally three times per week on a 28 day schedule in cycle 1. The dose will be escalated in cycle 2 to 90 mg orally three times per week on a 28 day schedule if there are no grade 3 or higher drug related toxicities. Therapy will continue until disease progression, intolerable toxicities or death.
干预措施: Mocetinostat (Drug)
结局指标
主要结局
Efficacy as Defined by Overall Response
时间窗: 1 year
as defined by overall response rate of Mocetinostat at one year in patients with relapsed/refractory DLBCL and FL who have inactivating mutations of acetyltransferase genes. Response will be measured according to the 2007 revised Cheson criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=50% decrease in sum of the product of the diameters (SPD) of up to 6 dominant lesions identified at baseline; Overall Response (OR) = CR + PR.
次要结局
- Number of Participants Evaluated for Toxicity According to the (NCI CTCAE) Version 4.0.(2 years)
- Event Free Survival(up to 17.8 months)
- Median Progression Free Survival/PFS(up to 17.8 months)
研究者
研究点 (1)
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