NCT00967044已完成1 期
Phase I/II of Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Everolimus With Panobinostat
研究概览
简要总结
Objectives:
Primary:
- Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the novel combination of everolimus + Panobinostat (LBH589) in a phase-I study in patients with relapsed lymphoma (Hodgkin and non-Hodgkin).
- Determine the safety and efficacy of this novel combination in a phase-II study in patients with relapsed Hodgkin and non-Hodgkin lymphoma
Secondary:
- Determine the in vivo effect of therapy on selected serum cytokines/chemokines (TGF-beta, thymus and activation-regulated chemokine (TARC), IL-6, IL-10, VEGF).
- Examine pre-treatment level of selected molecular targets (HDACs 1-11, STAT6, pSTAT6, STAT3, pSTAT3, Myc, Akt, Pichia anomala killer toxin (pAkt), S6, pS6, p21, cyclin D1) in primary lymphoma cells and the surrounding reactive inflammatory cells obtained by core needle biopsies from patients with relapsed lymphoma.
- Examine the correlation between molecular and biologic markers and clinical response and/or treatment-related toxicity.
详细描述
Phase I:
The Study Drugs:
Both panobinostat and everolimus are designed to block cancer cells from multiplying. Everolimus may also stop the growth of new blood vessels that help tumor growth. As a result, the cancer cells may grow more slowly or die.
Study Groups:
If you are found to be eligible to take part in this phase of the study, you will be assigned to a study group based on when you joined this study. Up to 5 groups of 3-6 participants will be enrolled in this phase of the study.
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 confirmed Hodgkin or non Hodgkin's lymphoma
- •Relapsed or refractory after standard treatments and with no curative option with conventional therapy
- •No evidence of cerebral or meningeal involvement by lymphoma
- •Age >= 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- •Life expectancy of at least 3 months
- •Signed informed consent form prior to enrollment
- •Patients must meet the following laboratory criteria: Aspartate aminotransferase (AST)/serum glutamate oxaloacetate transaminase (SGOT) and ALT/serum glutamate pyruvate transaminase (SGPT) </= 2.5 * upper limit of normal (ULN) ) or </= 5.0 x ULN if the transaminase elevation is due to lymphoma involvement, Serum bilirubin </= 1.5 * ULN, Serum creatinine </=1.5 * ULN free T4 within normal limits (WNL) (patients may be on thyroid hormone replacement)
- •Patients must have at least one measurable site of disease
- •Adequate bone marrow function as shown by: Absolute neutrophil count (ANC) >/= 1.0 x 109/L, Platelets >/=100 x 109/L
- •Fasting serum cholesterol </=300 mg/dL OR </=7.75 mmol/L AND fasting triglycerides </= 2.5 * 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 24 hours before starting therapy.
- •Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study drug
排除标准
- •Burkitt's lymphoma, Lymphoblastic lymphoma, Chronic lymphocytic leukemia (Small lymphocytic lymphoma may be included)
- •Chemotherapy or radiation therapy or other investigational agents within 4 weeks prior to entering the study
- •Previous radioimmunotherapy within 12 weeks
- •Prior therapy with HDAC or [1] mammalian target of rapamycin (mTOR) inhibitors i.e. temsirolimus, vorinostat (the list is not inclusive of investigational agents in these classes of drugs)
- •Patient with known HIV infection
- •Known active viral hepatitis
- •Any serious active disease or co-morbid condition, which in the opinion of the principle investigator, will interfere with the safety or with compliance with the study
- •Impaired cardiac function including any one of the following: • Screening ECG with a corrected QT interval (QTc) > 450 msec confirmed by the investigator prior to enrollment to the study • Patients with congenital long QT syndrome • History of sustained ventricular tachycardia • Any history of ventricular fibrillation or torsades de pointes • Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate >= 50 beats per minute are eligible.
- •Impaired cardiac function including any one of the following continued: • Patients with a myocardial infarction or unstable angina within 6 months from registration on study • Congestive heart failure (NY Heart Association class III or IV) • Right bundle branch block and left anterior hemiblock (bifascicular block) • Uncontrolled hypertension
- •Concomitant use of drugs with a risk of causing torsades de pointes
- •Patients with unresolved diarrhea Common Toxicity Criteria for Adverse Effects (CTCAE) grade 1
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral PANOBINOSTAT or everolimus.
- •Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception.
- •Male patients whose sexual partners are WOCBP not using effective birth control
- •Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, basal or squamous cell carcinoma of the skin, or early stage prostate carcinoma.
- •Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required
- •Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
- •Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone <= 20 mg. Topical or inhaled corticosteroids are allowed.
- •Patients should not receive immunization with attenuated live vaccines within one week of study registration or during study period
- •Chronic obstructive pulmonary disease (COPD) or asthma requiring therapy
- •Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
- •Active (acute or chronic) uncontrolled severe infection, requiring oral or intravenous antibiotics.
- •Patients receiving treatment on another clinical research trial.
研究组 & 干预措施
Panobinostat + Everolimus
Experimental
Panobinostat (LBH589) Plus Everolimus (RAD001)
干预措施: Panobinostat (Drug)
Panobinostat + Everolimus
Experimental
Panobinostat (LBH589) Plus Everolimus (RAD001)
干预措施: Everolimus (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Everolimus With Panobinostat
时间窗: 28 day treatment cycle
MTD of the novel combination of Everolimus + Panobinostat (LBH589) in a phase-I study in participants with relapsed lymphoma (Hodgkin and non-Hodgkin) where MTD is defined as the highest dose at which no more than 1 in 6 of the participants in the cohort experiences one or more dose limiting toxicities (DLTs) in the first 28 day treatment cycle. Thirty patients were enrolled onto four dose levels: Everolimus (mg, orally) 5, 5, 10, 10 daily or Panobinostat (mg, orally) 10, 20, 20, 30 three times per week. The MTD was established without the use of colony stimulating factor in cycle 1.
次要结局
未报告次要终点
研究者
研究点 (1)
Loading locations...
相似试验
Unknown
1 期
Phase I/II Study With Oral Panobinostat Maintenance Therapy Following Allogeneic Stem Cell Transplantation in Patients With High Risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)Acute Myeloid LeukemiaMyelodysplastic SyndromeNCT01451268Johann Wolfgang Goethe University Hospital62
终止
1 期
A Trial of Panobinostat and Trastuzumab for Adult Female Patients With HER2 Positive Metastatic Breast Cancer (MBC) Whose Disease Has Progressed on or After TrastuzumabBreast CancerNCT00567879Novartis Pharmaceuticals56
已完成
1 期
Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast CancerBrain MetastasesHER2 PositiveMetastatic Breast CancerNCT00614978Jules Bordet Institute18
撤回
1 期
Clinical Trial of BP1001 (Liposomal Grb2 Antisense Oligonucleotide) in Combination With Dasatinib in Patients With Ph + CML Who Have Failed TKI, Ph+ AML, Ph+ MDSChronic Myelogenous Leukemia, Ph1-PositiveAcute Myeloid LeukemiaMyelodysplastic SyndromeNCT02923986Bio-Path Holdings, Inc.
已完成
1 期
Panobinostat Plus Ifosfamide, Carboplatin, and Etoposide (ICE) Compared With ICE For Relapsed Hodgkin LymphomaHodgkin's LymphomaNCT01169636M.D. Anderson Cancer Center62