A Phase 3, Randomized, Open-Label Study Comparing the Efficacy and Safety of the Combination of Beleodaq-CHOP or Folotyn-COP to the CHOP Regimen Alone in Newly Diagnosed Patients With Peripheral T-Cell Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 504
- 试验地点
- 134
- 主要终点
- PFS
研究概览
简要总结
Part 1: This is a 5 Arm study primarily to determine the best dose out of the two dose levels of Belinostat and Pralatrexate combined with CHOP/COP in newly diagnosed PTCL patients based on Safety for part 2 study.
Part 2 (Efficacy and Safety): This is a 3 Arm study. Patients with previously untreated PTCL will be randomized 1:1:1 into 1 of 3 treatment groups: 2 experimental treatment groups (Bel-CHOP or Fol-COP) or 1 active comparator treatment group (CHOP). Patients will be treated for up to 6 cycles. The primary objective is to compare the Progression Free Survival of patients with newly diagnosed PTCL treated for up to 6 cycles with Beleodaq (belinostat) in combination with CHOP (Bel-CHOP) or Folotyn (pralatrexate injection) in combination with COP (Fol-COP) to CHOP alone.
详细描述
Study Design and Treatment Plan:
Part 1: Dose Finding
It is a randomized, open label, multicenter study in patients with PTCL who have not been previously treated and the control arm is CHOP, COP, is the CHOP regimen without Doxorubicin (H). Two investigational agents are separately added to C(H)OP, Belinostat for Bel-CHOP and Pralatrexate for FOL-COP. In this first part, each investigational arm will have two dose levels which will be compared with CHOP as reference. Treatment will be randomized in five arms:
- Group 1a (Bel-CHOP) Belinostat 600 mg/m2
- Group 1b (Bel-CHOP) Belinostat 1000 mg/m2
- Group 2a (Fol-COP) Pralatrexate 20 mg/m2
- Group 2b (Fol-COP) Pralatrexate 30 mg/m2
- Group 3 for CHOP alone. Analysis will be done when 75 patients have received their planned treatment cycles to evaluate treatment compliance.
Approximately 20 patients will be enrolled into each group and receive at least one cycle of drug thus 15 patients are expected to be evaluated with their planned treatment of 6 cycles completed. The safety data will be evaluated to select the proper dose for Belinostat -CHOP and Pralatrexate-COP for the Part 2 study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
None - Open Label
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
- •Patient with newly diagnosed, untreated histology-proven PTCL based on local pathology review who is eligible for receiving, Belinostat, Pralatrexate, and CHOP. Pathology material must be available at the site for each patient before enrollment so that it can be sent to the Sponsor (or designee) for later confirmation. The following subtypes, as defined by the updated World Health Organization (WHO) classification, may be included. This information should be available for eligibility:
- •Pathology subtype:
- •Peripheral T-cell lymphoma, not otherwise specified
- •Angioimmunoblastic T-cell lymphoma
- •Anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) patients are eligible only if Brentuximab Vedotin (BV) is not commercially approved for use, not available in the country or patient is contraindicated to receive BV.
- •Follicular T-cell lymphoma
- •Others: Extra-nodal natural killer/T-cell lymphoma, nasal type; enteropathy-associated T-cell lymphoma; hepatosplenic T-cell lymphoma; and subcutaneous panniculitis-like T-cell lymphoma
- •CD30 expression and T-cell Follicular Helper (TFH) phenotype status must be available for documentation.
- •Patient has at least 1 site of measurable disease according to Response Evaluation Criteria in Lymphoma (RECIL) 2017 criteria as assessed by the local Investigator (Appendix 3)
- •Patient has an Eastern Cooperative Oncology Group performance (ECOG) status ≤2
- •For Part 1 (Dose Finding) - Patient has adequate hematological, hepatic, and renal function as defined by:
- •Absolute neutrophil count ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bone marrow involvement
- •Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of bone marrow involvement
- •Total bilirubin ≤1.5 mg/dL
- •Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3×upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma)
- •Calculated creatinine clearance of ≥ 60 mL/min
- •Part 2 (Efficacy and Safety) - disease related hypoplasia, hepatological or renal dysfunction can be included if any of the treatment groups can be administered based on package insert recommendation with the following restrictions:
- •Absolute neutrophil count ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bone marrow involvement
- •Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of bone marrow involvement
- •Total bilirubin ≤1.5 mg/dL
- •Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3 x the upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma)
- •Calculated creatinine clearance of ≥ 60 mL/min
- •UGT1A1 genotype has been characterized (see Belinostat dose modifications if abnormal) and must be available for documentation.
- •Patient must be willing and capable of giving written informed consent and must be able to adhere to dosing and visit schedules and meet all study requirements
- •Patient (male or female) is at least 18 years of age at the time of informed consent
- •Patient is willing to practice 2 forms of contraception, one of which must be a barrier method, from study entry until at least 6 months after the last dose of study treatment.
- •Females of childbearing potential must have a negative urine pregnancy test within 4 weeks prior to the first day of study treatment. Females who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) or are surgically sterilized do not require this test.
排除标准
- •A patient will not be eligible for inclusion if ANY of the criteria listed below apply:
- •Patients with a diagnosis of:
- •Precursor T-cell lymphoma or leukemia
- •Adult T-cell lymphoma/leukemia
- •T-cell prolymphocytic leukemia
- •T-cell large granular lymphocytic leukemia
- •Primary cutaneous type ALCL
- •Cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome)
- •ALCL if they can be treated with Brentuximab Vedotin (BV)
- •Patients taking drugs which are potent UGT1A1 inhibitors must discontinue one week before randomization; drug can be resumed if the treatment doesn't include belinostat
- •Patient with an active concurrent malignancy/life-threatening disease with the exception of non melanoma skin tumors and in situ cervical cancer if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease. If there is a history of prior malignancies/life-threatening diseases, the patient must be disease free for at least 5 years
- •Prior histone deacetylase (HDAC) inhibitor or pralatrexate therapy
- •Any known cardiac abnormalities such as baseline prolongation of QT/corrected QT (QTc) interval (i.e. demonstration of a QTc interval >450 msec); long QT syndrome; myocardial infarction within 6 months prior to starting study; history of significant cardiovascular disease; the required use of a concomitant medication that may cause Torsades de Pointes
- •Patient with uncontrolled hypertension
- •Patients status on the following:
- •Has a known HIV-positive diagnosis with uncontrolled and detectable viral load
- •Has Hepatitis B or Hepatitis C virus diagnosis with uncontrolled and detectable viral load or immunological evidence of chronic active disease
- •Patient with central nervous system metastasis
- •Patient with an active uncontrolled infection, underlying medical condition, laboratory abnormality, or other serious illness that would impair the ability of the patient to receive protocol treatment
- •Patient who has used any investigational drugs, biologics, or devices within 28 days prior to study treatment or plans to use any of these during the course of the study
- •Patient with a known history of drug or alcohol abuse
- •Pregnant or breastfeeding women
研究组 & 干预措施
Group 1a
Group 1a Belinostat 600 mg/m2 + CHOP
干预措施: Belinostat Injection (Drug)
Group 1b
Group 1b Belinostat 1000 mg/m2 + CHOP
干预措施: Belinostat Injection (Drug)
Group 2a
Group 2a Pralatrexate 20 mg/m2 + COP
干预措施: Pralatrexate Injection (Drug)
Group 2a
Group 2a Pralatrexate 20 mg/m2 + COP
干预措施: COP (Drug)
Group 2b
Group 2b Pralatrexate 30 mg/m2 + COP
干预措施: Pralatrexate Injection (Drug)
Group 2b
Group 2b Pralatrexate 30 mg/m2 + COP
干预措施: COP (Drug)
Group 1a
Group 1a Belinostat 600 mg/m2 + CHOP
干预措施: CHOP (Drug)
Group 3
CHOP
干预措施: CHOP (Drug)
Group 1b
Group 1b Belinostat 1000 mg/m2 + CHOP
干预措施: CHOP (Drug)
结局指标
主要结局
PFS
时间窗: 4.5 years
Progression-free survival is determined from randomization to the first documented Progression of Disease or death, whichever occurs first.
次要结局
- Overall survival(8 years)