PD-1 Inhibition With Nivolumab for the Treatment of Patients With Acute Myeloid Leukemia in Remission at High Risk for Relapse
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Recurrence-free Survival Rate
研究概览
简要总结
This phase II trial studies how well nivolumab works in treating patients with acute myeloid leukemia that has decreased or disappeared but may still be in the body (remission), and is at high risk for returning (relapse). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the anti-leukemic effects of nivolumab in patients with acute myeloid leukemia (AML) who have achieved a 1st complete remission (CR) after induction chemotherapy and consolidation chemotherapy and have high risk for relapse, or have achieved a 2nd CR.
SECONDARY OBJECTIVES:
I. To evaluate the immunologic responses to nivolumab among patients with AML in CR status post standard chemotherapy.
II. To determine whether response to nivolumab correlates with immunologic responses.
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
- •Patients with AML in remission (defined as CR, CR with incomplete platelet recovery -CRp-, CR with incomplete hematologic recovery -CRi-, or partial remission defined as a bone marrow with < 10% blasts after therapy with or without hematologic recovery)
- •High risk for relapse defined as: 1st CR with high risk features for relapse (including history of prior malignancy treated with chemotherapy or radiotherapy, or history of myelodysplastic syndrome, myeloproliferative disorder, chronic myelomonocytic leukemia, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN] or other hematologic malignancy thought to have evolved to AML [i.e., secondary AML, (sAML)]; high risk cytogenetics at diagnosis; fms-related tyrosine kinase 3 [FLT3] mutated at diagnosis; or presence or minimal residual disease assessed by polymerase chain reaction [PCR], cytogenetics, and/or flow cytometry at time of enrollment) 2nd CR regardless of disease characteristics at the time of diagnosis
- •Have received induction chemotherapy and at least one cycle of consolidation chemotherapy; patients should have achieved a CR within 12 months of enrollment onto protocol
- •No further chemotherapy or stem cell transplant (SCT) planned at the time of enrollment
- •Creatinine =< 1.5 x upper limit of normal (ULN)
- •Serum bilirubin =< 1.5 x ULN
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (b-hCG) pregnancy test result within 24 hours prior to the first dose of treatment and must agree to use an effective contraception method during the study and for 23 weeks after the last dose of the study drug; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy
- •Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 31 weeks following the last dose of study drug
- •Patients or their legally authorized representative must provide written informed consent
排除标准
- •History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses)
- •Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 2 weeks prior to the first dose of the study drugs
- •Patients with any other known concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure New York Heart Association [NYHA] class III or IV, myocardial infarction within 6 months, and poorly controlled hypertension; chronic renal failure; or active uncontrolled infection) which, in the opinion of the investigator could compromise participation in the study
- •Patients unwilling or unable to comply with the protocol
- •Patients who are on steroids (> 10 mg/day or equivalent) or immune suppression medications
- •Patients with autoimmune diseases (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis])
- •Patients with a history of inflammatory bowel disease such as Crohn's disease and ulcerative colitis
- •Patients known to be positive for hepatitis B surface antigen expression or with active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months), or with known human immunodeficiency virus (HIV) infection
- •Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents
- •Females who are pregnant or lactating
- •Patients with history of previous immunomodulatory therapy (not including lenalidomide or thalidomide)
研究组 & 干预措施
Treatment (nivolumab)
Patients receive nivolumab IV over 1 hour on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After cycle 6, patients may receive nivolumab on day 1 only. After cycle 12, patients may receive nivolumab on day 1 of every 3 cycles. Patients experiencing disease progression may go back to receiving treatment on days 1 and 15 of each cycle.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (nivolumab)
Patients receive nivolumab IV over 1 hour on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After cycle 6, patients may receive nivolumab on day 1 only. After cycle 12, patients may receive nivolumab on day 1 of every 3 cycles. Patients experiencing disease progression may go back to receiving treatment on days 1 and 15 of each cycle.
干预措施: Nivolumab (Biological)
结局指标
主要结局
Recurrence-free Survival Rate
时间窗: Up to 7 years 9 months
Time from date of treatment start until the date of first objective documentation of disease-relapse.
次要结局
- Number of Participants With Immunologic Responses to Nivolumab Among Patients With Acute Myeloid Leukemia (AML) in Complete Remission (CR) Status Post Standard Chemotherapy(Every 2 cycles (+/-1 cycle) for the first 6 cycles, then every 3 months while on study, then as clinically indicated till relapse; up to 7 years, 9 months.)
- Time to Relapse(Up to 7 years 9 months)
- Number of Participants Who Changed From MRD Postive to MRD Negative During Therapy With Nibolumab(Every 2 cycles (+/-1 cycle) for the first 6 cycles, then every 3 months while on study, then as clinically indicated till relapse; up to 7 years, 9 months.)
- Overall Survival(Up to 7 years 9 months)