Romidepsin in Combination With CHOEP as First Line Treatment Before Hematopoietic Stem Cell Transplantation in Young Patients With Nodal Peripheral T-cell Lymphomas: a Phase I-II Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 89
- 试验地点
- 54
- 主要终点
- Dose-limiting toxicity (DLT) of Ro-CHOEP-21 (Phase I endpoint)
研究概览
简要总结
This is a multicenter study that includes two phases:
- A phase I study to define the maximum tolerated dose (MTD) of Romidepsin in addition to CHOEP-21 and to test the safety and feasibility of CHOEP-21 in combination with dose escalation of Romidepsin (8, 10, 12, 14 mg). The dose level defined as MTD of Romidepsin will be used for the subsequent phase II study.
- A phase II study to evaluate the efficacy (response rate, progression free survival and overall survival) and safety of Ro-CHOEP-21 incorporated into a treatment strategy including SCT.
详细描述
PHASE I A1) Induction phase Ro-CHOEP-21 x 3 cycles
- Romidepsin (dose escalation) starting dose: 12mg/ms iv day +1 and +8. Dose modification according to toxicity (14mg/ms day +1 and +8; 10mg/ms day +1 and +8; 8mg/ms day +1 and +8);
- CHOEP-21 (Doxorubicin 50 mg/ms iv day +1; Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1; Cyclophosphamide 750 mg/ms iv day +1; Etoposide 100mg/ms iv from day +1 to +3; Prednisone100 mg orally from days +1 to +5).
According to the response achieved after the first 3 Ro-CHOEP-21 cycles:
- PR or CR: Ro-CHOEP-21 for 3 additional cycles followed by phase A2
- SD or PD: Treatment failures, proceed to salvage according to each institutional policy.
A2) Stem cell mobilization and transplantation phase Response evaluation and one DHAP course followed by peripheral stem cell harvesting.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 e ≤ 65 years
- •Peripheral T-cell lymphomas at diagnosis including: PTCL-NOS, AITL including other nodal TFH, ALK-ALCL
- •Stage II-IV
- •Written informed consent
- •No prior treatment for lymphoma
- •No Central Nervous System (CNS) disease (meningeal and/or brain involvement by lymphoma)
- •HIV negativity
- •Absence of active hepatitis C virus (HCV) infection
- •HBV negativity or patients with HBcAb +, HBsAg -, HBs Ab+/- with HBV-DNA negativity (in these patients Lamivudine prophylaxis is mandatory)
- •Levels of serum bilirubin, alkaline phosphatase and transaminases < 2 the upper normal limit, if not disease related
- •No psychiatric illness that precludes understanding concepts of the trial or signing informed consent
- •Ejection fraction > 50% and myocardial stroke in the last year nor QT prolongation (QTc interval < 480 msec using the Fridericia formula)
- •Clearance of creatinine > 60 ml/min if not disease related
- •Spirometry Diffusion Capacity (DLCO) > 50%
- •Absence of active, uncontrolled infection
- •For males and females of child-bearing potential, agreement upon the use of effective contraceptive methods prior to study entry, for the duration of study participation and in the following 90 days after discontinuation of study treatment
- •Availability of histological material for central review and pathobiological studies.
排除标准
- •Age <18 e > 65 years
- •Hystology other than: PTCL-NOS, AITL, ALK-ALCL
- •Prior treatment for lymphoma
- •Positive serologic markers for human immunodeficiency virus (HIV)
- •Active hepatitis B virus (HBV) infection
- •Active hepatitis C virus (HCV) infection
- •Levels of serum bilirubin, alkaline phosphatase and transaminases > 2 the upper normal limit, if not disease related
- •Ejection fraction < 50% and no myocardial stroke in the last year or QT prolongation (QTc interval > 480 msec using the Fridericia formula)
- •Clearance of creatinine < 60 ml/min if not disease related
- •Spirometry Diffusion Capacity (DLCO) < 50%
- •Pregnancy or lactation
- •Patient not agreeing to take adequate contraceptive measures during the study
- •Psychiatric disease that precludes understanding concepts of the trial or signing informed consent
- •Any active, uncontrolled infection
- •Prior history of malignancies other than PTCLs in the last five years (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast).
研究组 & 干预措施
Ro-CHOEP-21
During the Phase I It will administered Romidepsin (dose escalation) and the combination of CHOEP-21. During the Phase II It will administered Romidepsin (dose according to phase I) and the combination of CHOEP-21.
干预措施: Ro-CHOEP-21 (PHASE I) (Drug)
Ro-CHOEP-21
During the Phase I It will administered Romidepsin (dose escalation) and the combination of CHOEP-21. During the Phase II It will administered Romidepsin (dose according to phase I) and the combination of CHOEP-21.
干预措施: Ro-CHOEP-21 (PHASE II) (Drug)
结局指标
主要结局
Dose-limiting toxicity (DLT) of Ro-CHOEP-21 (Phase I endpoint)
时间窗: 3 months
Incidence of dose-limiting toxicity (DLT) of Ro-CHOEP-21, considering as maximum dose the one causing induction of any grade ≥ 3 non hematologic toxicity or a delay \>15 days of planned cycle date observed during the first two cycles according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)
Progression Free Survival (PFS) of Ro-CHOEP-21 (Phase II endpoint)
时间窗: 18 months
PFS on intention to treatment (ITT) evaluated at 18 months. PFS will be defined as the time between the date of enrolment and the date of disease progression, relapse or death from any cause.
次要结局
- Proportion of patients reaching SCT (Phase I endpoint)(6 months)
- ORR = Overall response rate (Phase I endpoint)(6 months)
- Overall Response Rate (ORR) and Complete Response (CR)(Phase II endpoint)(6 months)
- Event free survival (EFS) (Phase II endpoint)(18 months)
- Overall survival (OS) (Phase II endpoint)(24 months)
- Progression Free Survival (PFS) and Overall Survival (OS) (Phase II endpoint)(3 months)
- Toxicities (Phase II endpoint)(18 months)
- Higher toxicities (Phase II endpoint)(18 months)
- Treatment-related mortality (TRM) (Phase II Endpoint)(24 months)
- Graft-versus-host disease (GVHD) (Phase II endpoint)(24 months)