Phase I Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (RR-AML)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Number of Patients with Dose Limiting Toxicities as defined in Protocol Section 13.5
研究概览
简要总结
The study objective is to evaluate patient safety for patients with refractory and relapsed AML being treated with Ceramide NanoLiposome (CNL) .
详细描述
The research team has shown that C6 ceramide nanoliposome (CNL) has anti-cancer activity in laboratory models of AML and that when it is combined with other cancer-fighting drugs, it works better.
The primary goal of this study is to evaluate the safety of CNL given without other cancer treatments in patients with AML where either their initial treatment didn't work or it stopped working and the AML came back (refractory or relapsed AML, aka RR-AML). This study seeks to determine the right dose to start with in later studies when CNL is combined with other drugs in potential future studies.
CNL is given by intravenous (IV) infusion and will be given twice a week in this study. Participants will receive study treatment as long as it is considered safe for them to continue, though their disease status will be checked regularly to make sure that their disease has not gotten worse. Blood samples will be collected at many time-points to see how their bodies are responding to the drug and how long it stays in the blood.
The first patients in the study will start at one dose of the drug and, if that is shown to be safe, the next group will be treated at a slightly higher dose. Participants will be given CNL by intravenous (IV) infusion twice a week over about 2 hours and then they will be monitored for about 2 hours to make sure they don't have any bad side effects, but initially patients will be required to stay at the site for about 6 hours after the start of the infusion in order to get blood draws to see how long the drug stays active in their system.
Participants will have a bone marrow biopsy before their second "cycle" of drug (after about 1 month) and then again before their third cycle of drug in order to see how their disease is responding. After that, bone marrow biopsies will be about every other cycle based on what the study doctor recommends. If the doctor doesn't think that CNL is helping their disease, or if their doctor decides that it is not safe for them to continue, they will be taken off study treatment. Participants will be followed for safety and disease status for up to 6 months.
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
- 是
入选标准
- •Signed informed consent is obtained prior to conducting any study-specific screening procedures.
- •Willing and able to understand the nature of this study and to comply with the study and follow-up procedures.
- •Age and Disease: ≥ 18 years of age with refractory or relapsed AML
- •Refractory AML: Patients who fail to achieve a complete remission (CR) after one line of AML directed therapy
- •Relapsed AML: Patients who achieved a complete remission (CR) with one or more prior lines of AML directed therapy but then developed a relapse of AML.
- •Note: Patients are eligible even if they have not received intensive induction chemotherapy but have been treated with other AML directed therapy like hypomethylating agents (azacitidine, decitabine).
- •Eastern Cooperative Oncology Group (ECOG) performance status must be ≤2
- •Peripheral white blood cell (WBC) count <30,000/µL. For cyto-reduction, hydroxyurea is allowed during screening and through Cycle 2, Day 3 to reduce WBC count to < 30,000 µL.
- •Adequate organ function as evidenced by the following laboratory findings:
- •Total bilirubin ≤ 1.5 × upper limit of normal (ULN) or < 3 x ULN for patients with Gilbert-Meulengracht Syndrome
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
- •Creatinine clearance > 60 mL/min
- •QT-interval corrected according to Fridericia's formula (QTcF) < 450 ms on one electrocardiogram (ECG) at screening
排除标准
- •Patients meeting any of the following criteria are ineligible for study entry:
- •Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmias not well controlled with medication, myocardial infarction within the previous 6 months before registration, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients may not be receiving any other concurrent investigational agents, or have received any investigational agent within one week of registration.
- •Since the teratogenic potential of this combination is currently unknown, females who are pregnant or lactating are excluded.
- •History of any other malignancies within the preceding 12 months before registration with the exception of in-situ cancer, non-muscle invasive bladder cancer, prostate, basal or squamous cell skin cancer
- •Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction that, in the Investigator's opinion, could compromise the patient's safety or put the study outcomes at risk
- •Evidence of isolated extramedullary disease
- •Acute Promyelocytic Leukemia or AML with active central nervous system (CNS) involvement
- •Untreated severe (in the opinion of the treating investigator) infection
- •Active and uncontrolled infection with HIV (viral load is detectable by PCR)
- •Active infection with Hepatitis B virus (HbSAg positive or PCR with detectable viral load) or Hepatitis C virus (viral load detectable by PCR).
- •Past Hematopoietic stem cell transplant (HSCT) with active graft vs host disease, immunosuppression other than low dose prednisone (5 mg), or calcineurin inhibitors within the 4 weeks before registration
研究组 & 干预措施
Open Label Administration of Ceramide NanoLiposome
Ceramide NanoLiposome will be administered by Intravenous Dosing twice per week in accordance with the protocol relative to dose escalation. There is no placebo group or arm of the study.
干预措施: Ceramide NanoLiposome (Ceraxa) (Drug)
结局指标
主要结局
Number of Patients with Dose Limiting Toxicities as defined in Protocol Section 13.5
时间窗: At the end of the the first cycle of administration (each cycle is 28 days)
Dose Limiting Toxicities within the first cycle of CNL monotherapy. See section 13.5 of Protocol for the complete list of Dose Limiting Toxicities
Number of Patients with Adverse Events
时间窗: Through study completion, an average of 24 weeks
Number of Patients with Adverse Events
Severity of Adverse Events
时间窗: Through study completion, an average of 24 weeks
Severity of Adverse Event As Described in Protocol
Half Life of Study Drug
时间窗: Through cycle one, 28 days (each cycle is 28 days)
Time for drug to be reduced to half of the starting concentration (in minutes)
Ratio of C16/C24 Ceramides
时间窗: After one cycle of therapy (Day 28)
Ratio of Ceramide 16 to Ceramide 24 (ng of C16/ng of C18) from bone marrow biopsy
Clinical Response - Complete Response
时间窗: After Cycle Two (56 days)
Complete Response
Duration of therapy
时间窗: Through study completion, an average of 24 weeks
Duration of therapy provided as measured in days
Dose Levels achieved during study
时间窗: Through study completion, an average of 24 weeks
Dose levels administered in milligrams per m2
Duration of Adverse Events
时间窗: Length of Adverse Events as measured in days, measured through study completion, an average of 24 weeks
Duration of Adverse Events, As Described in Protocol, measured in days
Time to Maximum Study Drug (T Max)
时间窗: Through cycle one, 28 days (each cycle is 28 days)
Time to maximum concentration measured, in minutes
Study Drug Clearance
时间窗: Through cycle one, 28 days (each cycle is 28 days)
The Amount of Study Drug Cleared per unit time (Nanograms/Minute)
Clinical Response - Complete Response with Incomplete Hematologic Recovery (CRi)
时间窗: After Cycle Two (56 days)
Complete Response with Incomplete Hematological Recovery as defined by blasts in bone marrow
Clinical Response - Partial Remission
时间窗: After Cycle Two (56 days)
Partial Remission (as defined by blasts in bone marrow)
Concentration Max (C Max)
时间窗: Through cycle one, 28 days (each cycle is 28 days)
Maximum Serum Concentration measured, in nanograms/milliliter
次要结局
- Event Free Survival(From registration to 24 weeks after completion of experimental drug treatment)
- Overall Survival(From registration to 24 weeks following drug administration)
- Number of Patients with Grade 3 or 4 Adverse Events(Through study completion, an average of 24 weeks)
- Overall Response(Through study completion, an average of 24 weeks, and up to 24 weeks afterwards (total of 48 weeks))
- Quality of Life according to EORTC Quality of Life Questionnaire (QLQ) C30(Prior to starting study treatment, on day 1 of each cycle (each cycle is 28 days), and at end of treatment (which is expected to be 2 to 3 months (cycles) for most patients)