A Phase I/IB Study of Ipilimumab or Nivolumab in Patients With Relapsed Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 71
- 试验地点
- 13
- 主要终点
- Maximum tolerated dose (MTD) of ipilimumab according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Phase I)
研究概览
简要总结
This phase I/Ib trial studies the side effects and best dose of ipilimumab or nivolumab in treating patients with cancers of the blood and blood-forming tissues (hematologic cancers) that have returned after a period of improvement (relapsed) after donor stem cell transplant. Immunotherapy with monoclonal antibodies, such as ipilimumab and 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 determine the maximum-tolerated dose (MTD) of ipilimumab or nivolumab administered to patients with relapsed hematologic malignancies following allogeneic stem cell transplantation. (Phase I) II. To characterize the toxicity of ipilimumab or nivolumab administered at the MTD in this patient population. (Phase Ib)
SECONDARY OBJECTIVES:
I. To assess response rate. II. To assess progression free and overall survival.
EXPLORATORY OBJECTIVE:
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
- •Histologically or cytologically confirmed hematologic malignancy
- •The following malignancies will be considered eligible if progressive or persistent:
- •Chronic lymphocytic leukemia (CLL)
- •Non-Hodgkin lymphoma (NHL)
- •Hodgkin lymphoma (HL)
- •Multiple myeloma (MM)
- •Acute leukemia (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL])
- •Myelodysplastic syndrome (MDS)
- •Myeloproliferative neoplasms (MPN)
- •Chronic myeloid leukemia (CML)
- •Life expectancy of greater than 3 months
- •Must have undergone allogeneic hematopoietic stem cell transplantation (HSCT) (regardless of stem cell source)
- •Must have baseline donor T cell chimerism of >= 20%
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (unless due to Gilbert's disease or disease-related hemolysis, then =< 3.0 x ULN)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN
- •Creatinine =< 1.5 x institutional ULN
- •Prednisone dose =< 5 mg/day and off all other systemic immunosuppressive medications for at least 4 weeks prior to study entry
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Participants who have had anti-tumor therapy or other investigational agents within 4 weeks prior to registration (6 weeks for nitrosoureas or mitomycin C), or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to registration
- •Patients with prior history of or active severe (grade 3 or 4) acute graft-versus-host disease (GVHD)
- •Patients with a history of prior treatment with ipilimumab, anti-programmed cell death protein 1 (PD 1) antibody, or cluster of differentiation (CD)137 agonist therapy are ineligible for the ipilimumab arm, but are eligible for the nivolumab arm
- •Patients who have had donor lymphocyte infusion (DLI) within 8 weeks prior to registration
- •Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]) and motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and myasthenia gravis); patients with Hashimoto's thyroiditis are eligible to go on study
- •Patients with known chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections should be excluded
- •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
- •Pregnant women are excluded from this study because ipilimumab and nivolumab are immunomodulatory agents with the potential for teratogenic or abortifacient effects; the effects of ipilimumab and nivolumab on the developing human fetus are unknown; for this reason and because immunomodulatory agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study or within 23 weeks after the last dose of study drug, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for at least 31 weeks after completion of ipilimumab or nivolumab administration
研究组 & 干预措施
Treatment (ipilimumab, nivolumab)
See Detailed Description.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (ipilimumab, nivolumab)
See Detailed Description.
干预措施: Nivolumab (Biological)
Treatment (ipilimumab, nivolumab)
See Detailed Description.
干预措施: Ipilimumab (Biological)
结局指标
主要结局
Maximum tolerated dose (MTD) of ipilimumab according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Phase I)
时间窗: At 12 weeks
Dose-limiting toxic (DLT) effects were defined as grade III or IV acute graft versus host disease (GVHD), grade 4 hematologic toxic effects unrelated to the underlying disease, or grade 3 nonhematologic toxic effects that did not improve to grade 1 with a 3-week dose delay. Immune-related adverse events that resolved to grade 1 or lower with the use of glucocorticoids were not considered to be dose-limiting toxic effects. We designated the observation period for toxic effects to be 12 weeks to capture delayed immunologic toxic effects.
Maximum tolerated dose (MTD) of nivolumab according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Phase I)
时间窗: At 12 weeks
Dose-limiting toxic (DLT) effects are defined as grade III or IV acute GVHD, grade 4 hematologic toxic effects unrelated to the underlying disease, or grade 3 nonhematologic toxic effects that did not improve to grade 1 with a 3-week dose delay. Immune-related adverse events that resolved to grade 1 or lower with the use of glucocorticoids were not considered to be dose-limiting toxic effects. We designated the observation period for toxic effects to be 12 weeks to capture delayed immunologic toxic effects.
Incidence of adverse events as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Phase Ib)
时间窗: Up to 1 year after completion of study treatment
A serious adverse event (SAE) is any adverse event, occurring at any dose and regardless of causality that 1) Results in death, 2) Is life-threatening, 3) Requires or prolongs inpatient hospitalization, 4) Results in persistent or significant disability/incapacity, 5) Is an important medical event when, based upon appropriate medical judgment, it may jeopardize the participant and require medical or surgical intervention to prevent one of the outcomes listed above.
次要结局
- Clinical response(Up to 1 year)
- Progression-free survival (PFS)(From start of treatment to time of objective disease progression, assessed up to 1 year)
- Overall survival (OS)(From the start of treatment to time of death, assessed up to 1 year)