NCT00742027已完成2 期
A Phase II Study of Oral Panobinostat in Adult Patients With Relapsed/Refractory Classical Hodgkins Lymphoma After High-dose Chemotherapy With Autologous Stem Cell Transplant
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 129
- 试验地点
- 14
- 主要终点
- Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria
研究概览
简要总结
This study evaluated the efficacy of oral panobinostat in participants with refractory/relapsed classical Hodgkins lymphoma (HL) who have received prior treatment with high dose chemotherapy and autologous stem cell transplant. Safety of panobinostat also was assessed. Other markers that may correlate with efficacy or safety were explored.
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
- •Participant age is ≥ 18 years.
- •Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Participant has a history of classical Hodgkin's Lymphoma (HL) (i.e. Nodular sclerosing, Mixed-cellularity, Lymphocyte-rich, Lymphocyte depleted).
- •Participant has progressive disease after receiving high dose chemotherapy with autologous hematopoietic stem cell transplant (AHSCT).
- •Note: If last therapy was ≥ 18 months ago, then biopsy should be performed to confirm diagnosis.
- •Note: Participant should have received ≤ 5 prior systemic treatment regimens (See Post-text supplement 2 for definitions and examples).
- •Note: Participant will be allowed on study who have also received an allogeneic hematopoietic stem cell transplant, however this therapy alone is not sufficient for inclusion into this study.
- •Participant has at least one site of measurable nodal disease at baseline ≥ 2.0 centimeter (cm) in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by computed tomography (CT) scan (magnetic resonance imaging [MRI] is allowed only if CT scan can not be performed).
- •Note: Participant with bone marrow involvement are eligible, but this criteria alone should not be used for disease measurement.
- •Participant has the following laboratory values (labs may be repeated, if needed, to obtain acceptable values before screen fail):
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/liter (L) [International System of Units {SI} units 1.5 x 10^9/L].
- •Platelet count ≥ 75 x 10^9/L.
- •Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution.
- •Note: Potassium, calcium, magnesium, sodium, and/or phosphorus supplements may be given to correct values that are < lower limits of normal (LLN). Post-correction values must not be deemed to be a clinically significant abnormality prior to participant being dosed.
- •Serum creatinine ≤ 1.5 x upper limits of normal (ULN).
- •Serum bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN, if participant has Gilbert syndrome).
- •Aspartate transaminase (AST)/ serum glutamic oxaloacetic transaminase (SGOT) and/or alanine transaminase (ALT)/ serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x ULN or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement.
- •Clinically euthyroid. Note: Participants are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
- •Written informed consent was obtained from the participant prior to any study-specific screening procedures.
- •Participant has the ability to swallow capsules or tablets.
排除标准
- •Participant has a history of prior treatment with a deacetylase (DAC) inhibitor including panobinostat.
- •Participant will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat treatment.
- •Participant has been treated with monoclonal antibody therapy (e.g., rituximab or anti CD-30 antibody, etc.) within 4 weeks of start of study treatment.
- •Participant has received chemotherapy or any investigational drug or undergone major surgery ≤ 2 weeks prior to starting study drug or whose side effects of such therapy have not resolved to ≤ grade
- •Participant has been treated with > 5 prior systemic lines of treatment (see Post-text supplement 2 for definitions and examples).
- •Participant has received prior radiation therapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to start of study treatment or whose side effects of such therapy have not resolved to ≤ grade
- •Participant is using any anti-cancer therapy concomitantly.
- •Participant treated with allogeneic hematopoietic stem cell transplant who is currently on or has received immunosuppressive therapy within 90 days prior to start of screening and/or have ≥ Grade 2 graft versus host disease (GvHD).
- •Participant has a history of another primary malignancy ≤ 3 years before study entry, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix.
- •Participant has a history of central nervous system (CNS) involvement with lymphoma.
- •Participant has impaired cardiac function including any of the following:
- •Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (<50 beats per minute [bpm]), QT interval (QTcF) > 450 milliseconds (msec) on screening electrocardiography (ECG), or right bundle branch block + left anterior hemiblock (bifascicular block).
- •Presence of atrial fibrillation (ventricular heart rate >100 bpm).
- •Previous history angina pectoris or acute myocardial infarction (MI) within 6 months.
- •Congestive heart failure (New York Heart Association functional classification III-IV) or baseline multigated acquisition (MUGA)/Echo shows left ventricular ejection fraction (LVEF) < 45%.
- •Participant has any other clinically significant heart disease (e.g., uncontrolled hypertension).
- •Participant has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection).
- •Participant has unresolved diarrhea ≥ grade
- •Participant has any other concurrent severe and/or uncontrolled medical condition(s) (e.g., uncontrolled diabetes mellitus, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol.
- •Participant has a known history of human immunodeficiency virus (HIV) seropositivity (screening HIV testing is not required).
- •Participant is using medications that have a relative risk of prolonging the QT interval or of inducing Torsade de Pointes, where such treatment cannot be discontinued or switched to a different medication prior to starting study drug.
- •Participant is a woman who is pregnant or breast feeding, or a women of childbearing potential (WOCBP) not willing to use a double method of contraception during the study through 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). WOCBP must have a negative serum pregnancy test at baseline.
- •Male participant whose sexual partner(s) are WOCBP who are not willing to use a double method of contraception, one of which includes a condom, during the study and for 3 months after the end of treatment.
- •Participants with any of the following contraindications to positron emission tomography (PET) are excluded from the [18F]- fludeoxyglucose (FDG) PET study (only applicable for centers participating in the PET study):
- •Fasting blood glucose above 200 milligrams per deciliter (mg/dL), at time of PET scan.
- •Inability to lay down for 60 minutes or has a history of claustrophobia.
- •Participant not at a participating center.
研究组 & 干预措施
Panobinostat
Experimental
Participants received panobinostat 40 mg, capsules, orally, thrice every week (i.e. days 1, 3 and 5), in each cycle of 21 days until unacceptable toxicity, disease progression, start of new anti-cancer therapy or withdrawal of consent (up to approximately 48 months).
干预措施: Panobinostat (Drug)
结局指标
主要结局
Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria
时间窗: From the start of the treatment of last participant up to 32 weeks
ORR was number of participants with best overall disease response of complete response(CR)/partial response(PR).Best overall disease response was best disease response recorded from start of treatment until disease progression/recurrence.CR=complete normalization of all index nodal,extranodal lesions,complete disappearance of all extranodal lesions.PR=50% decrease in SPD for up to 6 identified dominant lesions (splenic,hepatic nodules) from baseline.Stable=neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease (PD), reference smallest sum diameters while on study.Progression=50% increase in sum of longest diameter of all target lesions,from smallest sum of longest diameter of all target lesions recorded at or after baseline/a new lesion/progression of non-target lesions.Unknown is progression not documented,one/more of index lesions not assessed or have been assessed using a different method than baseline at the time of radiologic evaluation.
次要结局
- Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), And Deaths as a Measure of Safety and Tolerability of Panobinostat(Up to approximately 5 years)
- Maximum Observed Concentration (Cmax) of Panobinostat(Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose)
- Response Rate Based on Central Review of Computed Tomography (CT) Scan/Magnetic Resonance Imaging (MRI)(From start of treatment until progression/recurrence or start of a new cancer therapy (up to approximately 5 years))
- Duration of Overall Disease Response(From the start of treatment up to approximately 5 years)
- The Overall Survival (OS)(Baseline to date of death from any cause (up to approximately 5 years))
- Time To Overall Disease Response in Responders(From the start of treatment up to approximately 5 years)
- The Time to Reach Maximum Plasma Concentration (Tmax) of Panobinostat(Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose)
- Progression Free Survival (PFS)(From the start of treatment up to approximately 5 years)
- Area Under the Plasma Concentration-Time Curve From Time Zero to 28 Hours (AUC0-28) for Panobinostat(Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose)
- Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-∞) for Panobinostat(Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose)
研究者
研究点 (14)
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