Romidepsin Therapy in Conditioning and Maintenance in Patients With T-Cell Malignancies Receiving Allogeneic Stem Cell Transplant

Ohio State University Comprehensive Cancer Center1 个研究点分布在 1 个国家目标入组 23 人开始时间: 2017年12月8日最近更新: 2025年9月19日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Ohio State University Comprehensive Cancer Center
入组人数: 23
试验地点: 1
主要终点: Toxicity of Romidepsin with Busulfan and Fludarabine Conditioning Therapy for Allogeneic Stem Cell Transplantation

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 this clinical research study is to learn if giving romidepsin before and after a stem cell transplant in combination with fludarabine and busulfan can help to control leukemia or lymphoma. Researchers also want to learn the highest tolerable dose of romidepsin that can be given with this combination.

The safety of this combination and the safety of giving romidepsin after a stem cell transplant will also be studied.

This is an investigational study. Romidepsin is FDA approved and commercially available for the treatment of CTCL in patients who have received at least 1 systemic (affecting the whole body) therapy before. Busulfan and fludarabine are FDA approved and commercially available for use with a stem cell transplant.

The use of the combination of romidepsin, busulfan, and fludarabine to treat the type of leukemia or lymphoma you have is considered investigational.

Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.

详细描述

Study Parts and Study Drug Dose Levels:

If you are found to be eligible to take part in this study, you will start Part 1 of the study. During Part 1, you will receive the study drugs before having a stem cell transplant. If the disease is well controlled after the transplant and you are still eligible, you will start Part 2. During Part 2, you will continue to receive romidepsin. The study treatments given in each part are described in more detail below.

The dose of romidepsin you receive will depend on when you join this study. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of romidepsin is found.

All participants will receive the same dose level of fludarabine. Busulfan dose levels are explained below.

Study Drug Administration and Transplant (Part 1):

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

•Age 18 to 70 years of age.
•Diagnosis of either Cutaneous T-Cell Lymphoma; T-Prolymphocytic Leukemia; T-Large Granulocytic Leukemia; T-Lymphoblastic Leukemia/lymphoma; or Peripheral T-Cell Lymphoma, Natural Killer/T-cell lymphoma for whom allogeneic stem cell transplantation is indicated.
•An 10/10 or 8/8 HLA matched (high resolution typing at A, B, C, DRB1, DQ1) sibling or unrelated donor.
•EF>/= 50% on MUGA scan or Echocardiogram.
•FEV1, FVC and corrected DLCO >/= 40%.
•Adequate renal function, as defined by estimated serum creatinine clearance >/=50 ml/min (using the Cockcroft-Gault formula: creatinine clearance = [(140-age)*kg/(72*serum creatinine)] * 0.85 if female) and/or serum creatinine </=1.6 mg/dL. Renal function will be calculated using ideal body weight (IBW), unless a patient weights >40% of their IBW, then adjusted body weight will be utilized.
•Serum bilirubin </= 1.5 x upper limit of normal.
•SGOT and SGPT </= 2 x upper limit of normal.
•Able to sign informed consent.
•Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.

排除标准

•Patient with active CNS disease.
•Pregnancy (positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
•Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA >/=10,000 copies/mL, or >/= 2,000 IU/mL).
•Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.
•HIV infection.
•Hematopoetic Transplant Co-Morbidity Index (HCT-CI) >4 unless deemed clinically insignificant by primary investigator for patients receiving Time-Sequential Busulfan (total exposure 20000 umol-min).
•Active uncontrolled bacterial, viral or fungal infections.
•Exposure to other investigational drugs within 4 weeks before enrollment.
•Grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= grade
•Radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment.
•Prior whole brain irradiation.
•Prior autologous SCT in the prior 12 months.
•Congenital QT syndrome, QTc >500 ms.
•Myocardial infarction within 1 year of study entry. Subjects with a history of myocardial infarction between 6 and 12 months prior to study entry who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate;
•Other significant EKG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min);
•Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV. In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
•An EKG recorded at screening showing evidence of cardiac ischemia (ST depression depression of >/= 2 mm, measured from isoelectric line to the ST segment). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
•Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction <40% by MUGA scan or <50% by echocardiogram and/or MRI;
•A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);
•Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes;
•Uncontrolled hypertension, i.e., blood pressure (BP) of >/= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose and meet all other inclusion criteria; or,
•Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers).
•Patients taking drugs leading to significant QT prolongation where the interaction is too great to proceed with romidepsin.
•Concomitant use of CYP3A4 inhibitors where the interaction is thought too great to proceed with romidepsin.

研究组 & 干预措施

Romidepsin + Busulfan + Fludarabine + Stem Cell Transplant

Experimental

Part 1:

Busulfan administered at the dose calculated to achieve a total (including first two doses delivered on Day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic studies. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Romidepsin dosed per actual body weight/actual body surface area. Romidepsin administered on Day -6, -5, -4, and -3 at escalating doses of 1 mg/m2, 2 mg/m2, and 3 mg/m2 by vein to determine the optimal dose. Participants receiving a graft from a matched unrelated donor receive rabbit Thymoglobulin; 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1. Stem cell infusion on Day 0.