A Phase I Study of DEC205mAb-NY-ESO-1 Fusion Protein (CDX-1401) Given With Adjuvant PoIylCLC in Conjunction With 5-Aza-2'Deoxycytidine (Decitabine) in Patients With MDS or Low Blast Count AML
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Incidence of toxicity graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
研究概览
简要总结
This phase I trial studies the side effects and immune response to DEC-205/NY-ESO-1 fusion protein CDX-1401 and decitabine in patients with myelodysplastic syndrome or acute myeloid leukemia. DEC-205-NY-ESO-1 fusion protein, called CDX-1401, is a full length NY-ESO-1 protein sequence fused to a monoclonal antibody against DEC-205, a surface marker present on many immune stimulatory cells. This drug is given with another substance called PolyICLC, which acts to provoke any immune stimulatory cells which encounter the NY-ESO-1-DEC-205 fusion protein to produce an immune response signal against NY-ESO-1. Immune cells which have thus been primed to react against NY-ESO-1 may then attack myelodysplastic or leukemic cells which express NY-ESO-1 after exposure to the drug decitabine. The chemotherapy drug decitabine is thought to act in several different ways, first, it may directly kill cancer cells, and secondly, the drug can cause cancer cells to re-express genes that are turned off by the cancer, including the gene for NY-ESO-1. Giving DEC-205/NY-ESO-1 fusion protein (CDX-1401) and polyICLC together with decitabine may allow the immune system to more effectively recognize cancer cells and kill them.
详细描述
PRIMARY OBJECTIVES:
I. Evaluate the safety of Anti-DEC-205-NY-ESOI (CDX-1401) fusion protein (DEC-205/NY-ESO-1 fusion protein CDX-1401) given in combination with decitabine 20 mg/m^2 intravenously.
SECONDARY OBJECTIVES:
I. To evaluate NY-ESO-1 specific cellular and humoral immunity by determination of NY-ESO-1 specific antibody, and T-cell clones following standard treatment with 5-aza-2'-deoxycytidine (decitabine) in conjunction with immune sensitization with Anti-DEC 205-NY-ESO-I fusion protein (CDX-1401).
II. To determine the impact of decitabine treatment on peripheral blood cells from patients treated in this manner on NY-ESO-1 target gene expression, NY-ESO protein expression, NY-ESO-1 promoter methylation, and global deoxyribonucleic acid (DNA) methylation.
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
- •Subjects with a confirmed diagnosis of:
- •International Prognostic Scoring System (IPSS) intermediate-I, interrnediate-2 or high-risk MDS including chronic myelomonocytic leukemia (CMML) or
- •Low blast count AML with =< 30% blasts previously classified as refractory anemia with excess blasts in transformation who have not been previously treated with a hypomethylating agent
- •Patients with IPSS intermediate-1 disease with an isolated deletion of chromosome 5q must have previously failed treatment with lenalidomide
- •Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- •Total bilirubin =< 2 x upper limit of normal (ULN)
- •Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
- •Serum creatinine =< 1.5 x ULN
- •Any human leukocyte antigen (HLA) type
- •Subjects of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after the last treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- •Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
排除标准
- •Subjects with life-threatening illnesses other than MDS, uncontrolled medical conditions or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study outcomes at risk
- •AML associated with inv(16); t(16;16); t(8;21) or t(15;17)
- •Subjects with uncontrolled or symptomatic arrhythmias, or any class 3 or 4 cardiac disease as defined by the New York Heart Association functional classification
- •Subjects with symptomatic central nervous system (CNS) disease which is not adequately controlled
- •Subjects who have received prior radiation therapy for extramedullary disease within 2 weeks of first dose
- •Subjects with human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Subjects who are being treated with systemic corticosteroids
- •Subjects who have hypersensitivity to decitabine
- •History of auto-immune disease (e.g. thyroiditis, lupus) except vitiligo
- •Pregnant or nursing female subjects
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive study drug
- •Received an investigational agent within 30 days prior to enrollment
- •Active malignancy with the exception of basal cell carcinoma, non-melanoma skin cancer, cervical carcinoma-in-situ; other prior malignancies in remission for less than 1 year
- •Subjects previously treated with an allogeneic stem cell transplant
研究组 & 干预措施
Treatment (CDX-1401, Poly ICLC, decitabine)
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 SC and ID and poly-ICLC SC on days -14 and 15 of course 1 and on day 15 for courses 2-4. Patients also receive decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (CDX-1401, Poly ICLC, decitabine)
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 SC and ID and poly-ICLC SC on days -14 and 15 of course 1 and on day 15 for courses 2-4. Patients also receive decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: DEC-205/NY-ESO-1 Fusion Protein CDX-1401 (Biological)
Treatment (CDX-1401, Poly ICLC, decitabine)
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 SC and ID and poly-ICLC SC on days -14 and 15 of course 1 and on day 15 for courses 2-4. Patients also receive decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Decitabine (Drug)
Treatment (CDX-1401, Poly ICLC, decitabine)
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 SC and ID and poly-ICLC SC on days -14 and 15 of course 1 and on day 15 for courses 2-4. Patients also receive decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Poly ICLC (Drug)
结局指标
主要结局
Incidence of toxicity graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
时间窗: Up to 30 days after last dose of study treatment
Toxicity rates will be described using upper one-sided 95% Clopper Pearson binomial confidence intervals.
次要结局
- Change in immune and molecular epigenetic response(Baseline to up to 16 weeks)