Phase I/II Study of Hyper-CVAD Plus RAD001 (Everolimus) for Patients With Relapsed or Refractory Acute Lymphocytic Leukemia (ALL)

M.D. Anderson Cancer Center1 个研究点分布在 1 个国家目标入组 24 人开始时间: 2009年11月最近更新: 2019年2月27日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: M.D. Anderson Cancer Center
入组人数: 24
试验地点: 1
主要终点: Maximum Tolerated Dose [MTD] Determination by Number of Participants With Dose Limiting Toxicity (DLT)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The goal of Phase I of this clinical research study is to find the highest tolerable dose of RAD001 (everolimus) when given in combination with the standard chemotherapy regimens to patients with ALL.

The goal of Phase II of this study is to learn if the drug combinations can help to control ALL. The safety of these drug combinations will be also studied in both phases.

详细描述

The Study Drugs:

Everolimus is designed to stop cancer cells from multiplying. It may also stop the growth of new blood vessels that help tumor growth, which may cause the tumor cells to die.

You will receive everolimus with 2 different chemotherapy combinations during alternating cycles. This means that you will receive 1 combination on Cycles 1, 3, 5, and 7 and the other combination during Cycles 2, 4, 6, and 8.

The first chemotherapy regimen is called hyper-CVAD. Hyper-CVAD includes cyclophosphamide, vincristine, Adriamycin (doxorubicin), and dexamethasone. This combination is designed to kill leukemia cells.

The other chemotherapy regimen includes the drugs methotrexate and ara-C (cytarabine). This combination is also designed to kill leukemia cells.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 10 Years 至 —（Child, Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Refractory or relapsed acute lymphocytic leukemia (ALL) or lymphoblastic lymphoma (LL). Patients expressing Philadelphia chromosome (Ph+) are eligible if they have failed a prior tyrosine kinase-containing therapy.
•Age >/= 10 years.
•Eastern Cooperative Oncology Group (ECOG) performance status </=
•Adequate liver function with serum bilirubin </= 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 2.5 x ULN, unless proven to be related to disease infiltration.
•Adequate renal function with serum creatinine </= 1.5 x ULN, unless proven to be related to disease infiltration.
•No symptomatic pulmonary disease. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) >/= 50% of expected, corrected for hemoglobin.
•Fasting serum cholesterol </= 300 mg/dL (or </= 7.75 mmol/L); fasting triglycerides </= 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
•Signed informed consent.

排除标准

•Systemic chemotherapy within 7 days (with the exception of hydroxyurea and/or dexamethasone) prior to starting therapy and recovered from persistent acute toxicity (> grade 1) from that therapy, unless there is evidence of rapidly progressive disease. Concurrent therapy for central nervous system (CNS) prophylaxis or treatment for CNS relapse is permitted.
•Prior treatment with or known hypersensitivity to an mammilian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus, everolimus).
•Major surgery within 4 weeks of start of study drug.
•Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix, or basal or squamous cell carcinomas of the skin.
•Severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study: a. Symptomatic congestive heart failure of New York Heart Association Class III or IV. b. Unstable angina pectoris or myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia. c. Uncontrolled severe infections. d. Liver disease such as cirrhosis, or severe hepatic impairment (Child-Pugh class C).
•continuation of #5: Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. Hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.
•Known history of HIV seropositivity.
•Impairment of gastrointestinal function of gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, malabsorption syndrome or small bowel resection).
•Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Childbearing potential is a sexually mature woman who: 1)has not undergone a hysterectomy or bilateral oophorectomy; 2)has not been naturally postmenopausal for at least 24 consecutive months. Adequate contraception must be used throughout the trial and for eight weeks after the last dose of study drug, by both sexes. (Women of child bearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of therapy.)
•Male patient whose sexual partner(s) are women of child bearing potential who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment.
•Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
•Patients who have developed pleural effusion while on dasatinib therapy.

研究组 & 干预措施

Phase I: RAD001 + Combination Chemo

Experimental

Optimal dose finding of Everolimus (RAD001) beginning dose 5 mg + two different chemotherapy combinations during alternating cycles, Hyper-CVAD on Cycles 1, 3, 5, & 7 and Methotrexate & Cytarabine (Ara-C) during Cycles 2, 4, 6, & 8.