A Phase 1b, Open-label Study of LY2510924, Idarubicin and Cytarabine in Patients With Relapsed or Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicity of LY2510924, Idarubicin and Cytarabine in Patients with Relapsed or Refractory Acute Myeloid Leukemia
研究概览
简要总结
The goal of this clinical research study is to learn about the safety of LY2510924 in combination with cytarabine and idarubicin in patients with relapsed or refractory AML. We will also study if LY2510924 in combination with cytarabine and idarubicin can help to control relapsed or refractory AML.
LY2510924 is designed to help cancer cells move from the bone marrow into the bloodstream, where they are exposed to chemotherapy (in this case, cytarabine and idarubicin).
This is an investigational study. LY2510924 is not FDA approved or commercially available. Its use in this study is investigational. Cytarabine and idarubicin are approved to treat certain types of leukemia. Their use in this study in combination with LY2510924 is investigational.
Up to 36 patients will take part in this study. All will be enrolled at MD Anderson.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 3 groups of up to 6 participants each will be enrolled in the Dose Escalation part of the study, and up to 18 participants will be enrolled in Dose Expansion part of the study.
If you are enrolled in the Dose Escalation part of the study, the dose of LY2510924 you receive will depend on when you join this study. The first group of participants will receive the lowest dose level of LY2510924. Each new group will receive a higher dose of LY2510924 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of LY2510924 is found.
If you are enrolled in the Dose Expansion part of the study, you will receive LY2510924 at the highest dose that was tolerated in the Dose Expansion part of the study.
All participants will also receive idarubicin and cytarabine. Your dose level will be assigned based on your age.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients with histologically or cytologically confirmed relapsed or refractory AML [except acute promyelocytic leukemia]; relapsed disease or refractory (refractory to a non-high-dose cytarabine-containing regimen only); receiving 1st, 2nd or 3rd salvage; any cytogenetic or molecular abnormality. Patients with secondary AML (after prior myelodysplasia or therapy for other cancers) will be included.
- •Patients with prior autologous and allogeneic hematopoietic stem cell transplantation are eligible if patients are off immunosuppression for greater than 14 days and have no evidence of active graft versus host disease (GVHD) except grade 1 skin GVHD.
- •Clinical laboratory values should be as follows: (a) White blood count < 30,000/µL; (b) Absolute Blasts in peripheral blood < 20,000 (treatment with Hydroxyurea is permitted up to 24 hrs prior to LY251092 administration to achieve blast counts < 20,000 prior to enrollment).
- •Patients must be 18-70 years old.
- •Patients must have a performance status of 0-2 (Zubrod scale).
- •Patients must have adequate renal function (serum creatinine less than or equal to 1.3 mg/dL). If creatinine is > 1 mg/dL the creatinine clearance should be > 40 mL/min as calculated using the Cockcroft-Gault formula.
- •Patients must have adequate hepatic function (bilirubin less than or equal to 2.0 mg/dl; serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 X the upper limit of normal [ULN] for the reference lab unless due to leukemia or congenital hemolytic disorder or bilirubin excretion disorder). Patients with hepatic dysfunction (SGOT/SGPT up to less than or equal to 5 X ULN) due to organ infiltration by disease may be eligible after discussion with the Principal Investigator and appropriate dose adjustments will be considered.
- •Patients must have normal cardiac ejection fraction (left ventricular ejection fraction [LVEF] greater than or equal to 50%).
- •Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study, in keeping with the policies of the hospital.
- •Negative urine or blood pregnancy test for women of childbearing potential.
- •Female patients must not be pregnant or lactating. Female patients of childbearing potential (including those <1 year post-menopausal) and male patients must agree to use contraception.
排除标准
- •Patients with untreated or uncontrolled life-threatening infection.
- •Patients who have received chemotherapy and/or radiation therapy within 2 weeks unless there is evidence of rapidly progressive disease. In the event that subjects have received chemotherapy < 2 weeks from the date of enrollment, they may be included provided they have recovered from the associated non-hematological toxicities to less than or equal to grade
- •Hydroxyurea is allowed up to 24 hours prior to starting therapy in the setting of rapidly proliferating disease.
- •Patients who have received an investigational anti-cancer drug within two weeks (or five half-lives, whichever is shorter) of LY251092 administration.
- •History of myocardial infarction or cerebrovascular accident within 6 months of enrollment date.
- •History of another malignancy. Exception: Patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible.
- •Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent or cooperate and participate in the study or with the interpretation of the results.
- •Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression (patients with controlled central nervous system (CNS) disease, i.e. asymptomatic and currently receiving concurrent intrathecal chemotherapy, are eligible upon discussion with the Principal InvestigatorI).
- •Known active Hepatitis B Virus (HBV), Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV) infection (patients with chronic or cleared HBV and HCV infection, are eligible).
研究组 & 干预措施
LY2510924 + Idarubicin + Cytarabine
Dose Escalation Phase: Starting dose level of LY2510924 is 10 mg subcutaneously each day of a 28 day cycle. Dose escalated in successive cohorts of patients. On Day 8, LY2510924 administered after bone marrow aspiration and/or biopsy is performed.
Dose Expansion Phase: LY2510924 given at the maximum tolerated dose (MTD) from Dose Escalation Phase.
Dose Escalation Phase: Idarubicin 12 mg/m2 by vein given on Days 8 and 9 of a 28 day cycle. In patients > 60 years of age Idarubicin given for 2 days.
Dose Expansion Phase: Idarubicin 8 mg/m2 by vein for 2 days.
Dose Escalation Phase: Cytarabine 1.5 gm/m2 by vein daily for 4 days (age < 60 years). In patients > 60 years of age Cytarabine given for 3 days only.
Dose Expansion Phase: Cytarabine 0.75 gm/m2 by vein for 3 days.
干预措施: LY2510924 (Drug)
LY2510924 + Idarubicin + Cytarabine
Dose Escalation Phase: Starting dose level of LY2510924 is 10 mg subcutaneously each day of a 28 day cycle. Dose escalated in successive cohorts of patients. On Day 8, LY2510924 administered after bone marrow aspiration and/or biopsy is performed.
Dose Expansion Phase: LY2510924 given at the maximum tolerated dose (MTD) from Dose Escalation Phase.
Dose Escalation Phase: Idarubicin 12 mg/m2 by vein given on Days 8 and 9 of a 28 day cycle. In patients > 60 years of age Idarubicin given for 2 days.
Dose Expansion Phase: Idarubicin 8 mg/m2 by vein for 2 days.
Dose Escalation Phase: Cytarabine 1.5 gm/m2 by vein daily for 4 days (age < 60 years). In patients > 60 years of age Cytarabine given for 3 days only.
Dose Expansion Phase: Cytarabine 0.75 gm/m2 by vein for 3 days.
干预措施: Idarubicin (Drug)
LY2510924 + Idarubicin + Cytarabine
Dose Escalation Phase: Starting dose level of LY2510924 is 10 mg subcutaneously each day of a 28 day cycle. Dose escalated in successive cohorts of patients. On Day 8, LY2510924 administered after bone marrow aspiration and/or biopsy is performed.
Dose Expansion Phase: LY2510924 given at the maximum tolerated dose (MTD) from Dose Escalation Phase.
Dose Escalation Phase: Idarubicin 12 mg/m2 by vein given on Days 8 and 9 of a 28 day cycle. In patients > 60 years of age Idarubicin given for 2 days.
Dose Expansion Phase: Idarubicin 8 mg/m2 by vein for 2 days.
Dose Escalation Phase: Cytarabine 1.5 gm/m2 by vein daily for 4 days (age < 60 years). In patients > 60 years of age Cytarabine given for 3 days only.
Dose Expansion Phase: Cytarabine 0.75 gm/m2 by vein for 3 days.
干预措施: Cytarabine (Drug)
结局指标
主要结局
Dose Limiting Toxicity of LY2510924, Idarubicin and Cytarabine in Patients with Relapsed or Refractory Acute Myeloid Leukemia
时间窗: 30 days post transplant
Dose-limiting toxicity (DLT) defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness or concomitant medications. To be considered a DLT such toxicity must be possibly, probably or definitely related to LY2510924. Toxicity evaluated using the National Cancer Institute (NCI) Version 4.0 criteria.
次要结局
- Response of LY2510924, Idarubicin and Cytarabine in Patients with Relapsed or Refractory Acute Myeloid Leukemia(56 days)