A Phase 3, Randomised, Parallel-Group, Active-Controlled, Double-Blind Study to Demonstrate Equivalence of Pharmacokinetics and Noninferiority of Efficacy for CT-P10 in Comparison With Rituxan, Each Administered in Combination With Cyclophosphamide, Vincristine, and Prednisone (CVP) in Patients With Advanced Follicular Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celltrion
- 入组人数
- 140
- 主要终点
- Maximum Serum Concentration at Steady State (Cmax,ss)
研究概览
简要总结
This study is a Phase 3 prospective, randomised, parallel-group, active controlled, double blind, multicentre, international study with 2 coprimary endpoints designed to demonstrate equivalence in pharmacokinetics (Part 1), as well as noninferiority in efficacy (Part 2), of CT-P10 to Rituxan when coadministered with CVP and to assess efficacy and safety in patients with advanced (stage III-IV) FL. Part 1 and Part 2 of the study will run in parallel.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 is male or female older than 18 years.
- •Patient has histologically confirmed FL according to the World Health Organization 2008 classification (Jaffe 2009); grades 1 to 3a based on local laboratory review.
- •Patient has at least 1 measurable tumour mass that has not previously been irradiated, and the mass must be:
- •greater than 1.5 cm in the longest dimension or
- •between 1.1 and 1.5 cm in the longest dimension and greater than 1.0 cm in the shortest axis
- •Patient has confirmed CD20+ lymphoma, as assessed by local laboratory review. (Tissue obtained within 6 months before Day 1 of Cycle 1 will be reviewed by a central independent reviewer to detect pathological type.)
- •Patient has Ann Arbor stage III or IV disease.
排除标准
- •Patient has received rituximab (or a rituximab biosimilar), cyclophosphamide, or vincristine.
- •Patient has allergies or hypersensitivity to murine, chimeric, human or humanised proteins, cyclophosphamide, vincristine, or prednisone.
- •Patient has evidence of histological transformation to high-grade or diffuse large B-cell lymphoma.
- •Patient has known central nervous system involvement.
- •Patient has received previous treatment for NHL:
- •Previous treatment including chemotherapy, radiotherapy, immunotherapy, and/or surgery (except previous biopsy)
- •All doses of corticoid therapy for treatment of NHL
- •Corticoid therapy during the previous 4 weeks from Day 1 of Cycle 1 with prednisone >20 mg per day for the treatment for any purpose
研究组 & 干预措施
CT-P10
Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period.
Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
干预措施: CT-P10 (Biological)
CT-P10
Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period.
Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
干预措施: Cyclophosphamide (Drug)
CT-P10
Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period.
Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
干预措施: Vincristine (Drug)
CT-P10
Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period.
Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
干预措施: Prednisone (Drug)
Rituxan
Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period.
Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
干预措施: Rituxan (Biological)
Rituxan
Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period.
Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
干预措施: Cyclophosphamide (Drug)
Rituxan
Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period.
Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
干预措施: Vincristine (Drug)
Rituxan
Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period.
Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
干预措施: Prednisone (Drug)
结局指标
主要结局
Maximum Serum Concentration at Steady State (Cmax,ss)
时间窗: Core Cycle 4 (Week 12)
Cmax,ss: Maximum concentration of drug in plasma at steady state on administering a fixed dose at equal dosing intervals. PK sampling was done at pre-dose and 1 hour after the end of infusion (EOI) at Core Cycles 1-3 and 5-8. At Core Cycle 4 (i.e. steady state), intensive PK samplings were done as follows: predose, EOI, 1 hour after EOI, 24 hour after EOI, 168 hour after EOI, 336 hour after EOI, 504 hour after EOI. Lastly, one sample at any time of the end of treatment (EOT) 1 visit was obtained.
Overall Response Rate (ORR) According to the 1999 International Working Group (IWG) Criteria
时间窗: During the Core Study Period (up to 8 cycles; Week 24)
ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed complete response (CRu), or partial response (PR) by central review. Per 1999 IWG criteria, the disease status was assessed by using contrasted CT, and CR, CRu, and PR were defined as followings; CR=Disappearance of all clinical/radiographic evidence of disease: regression of lymph nodes to normal size, absence of B-symptoms, bone marrow involvement, and organomegaly, and normal LDH level; CRu=Regression of measurable disease: \>=75% decrease in SPD of target lesions and in each target lesions. no increase in the size of non-target lesions, neither new lesion nor organomegaly measured; PR=Regression of measurable disease: \>=50% decrease in SPD of target lesions and no evidence of disease progression.
Area Under the Serum Concentration-time Curve at Steady State (AUCtau)
时间窗: Core Cycle 4 (Week 12)
AUCtau: Area under the plasma drug concentration-time curve within a dosing interval at steady state. PK sampling was done at pre-dose and 1 hour after the end of infusion (EOI) at Core Cycles 1-3 and 5-8. At Core Cycle 4 (i.e. steady state), intensive PK samplings were done as follows: predose, EOI, 1 hour after EOI, 24 hour after EOI, 168 hour after EOI, 336 hour after EOI, 504 hour after EOI. Lastly, one sample at any time of the end of treatment (EOT) 1 visit was obtained.
次要结局
- B-cell Kinetics (B-cell Depletion and Recovery)(Cycles 1 to 8 during the Core Study Period)