A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Comparing the Efficacy and Safety of Tafasitamab Plus Lenalidomide in Addition to R-CHOP Versus R-CHOP in Previously Untreated, High-intermediate and High-risk Patients With Newly-diagnosed Diffuse Large B-cell Lymphoma (DLBCL)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 899
- 试验地点
- 4
- 主要终点
- PFS-INV
研究概览
简要总结
This is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial designed to compare the efficacy and safety of the humanized monoclonal anti CD19 antibody tafasitamab plus lenalidomide in addition to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) versus R-CHOP in previously untreated, high-intermediate and high-risk patients with newly-diagnosed DLBCL
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Previously untreated patients with local biopsy-proven, CD20-positive DLBCL, including one of the following diagnoses by 2016 World Health Organization (WHO) classification of lymphoid neoplasms are eligible:
- •DLBCL, NOS including GCB type, ABC type
- •T-cell rich large BCL
- •Epstein-Barr virus-positive DLBCL, NOS
- •Anaplastic lymphoma kinase (ALK)-positive large BCL
- •Human herpes virus-8 (HHV8)-positive DLBCL, NOS
- •High-grade BCL with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements (double-hit or triple-hit lymphoma). Please note: Patients must be appropriate candidates for R-CHOP. If an investigator deems a patient with a known double- or triple-hit lymphoma (HGBL) should be treated more aggressively (e.g. dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab [DA-EPOCH-R] or cyclophosphamide, vincristine, doxorubicin and dexamethasone (CVAD) followed by methotrexate and cytarabine [Hyper CVAD]), this patient would not be considered eligible for this study
- •DLBCL coexistent with either follicular lymphoma (FL) of any grade, gastric MALT lymphoma or non-gastric MALT lymphoma
- •FL grade 3b
- •Availability of archival or freshly collected tumor tissue sent for retrospective central pathology review
- •IPI status of 3 to 5 (for patients > 60 years of age) or aaIPI 2 to 3 (for patients ≤ 60 years of age)
- •Diagnosis to treatment interval, defined as the time between the date of DLBCL diagnosis (date of the first biopsy specimen containing B Cell lymphoma according to the local pathology report) and the start of treatment (C1D1) ≤ 28 days
- •ECOG performance status of 0, 1, or 2
- •Left ventricular ejection fraction equal to or greater 50% as assessed by local echocardiography or cardiac multi-gated acquisition (MUGA) scan
- •Adequate hematologic function
- •Female participants: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and refrain from breast feeding and donating eggs; agreement to ongoing pregnancy testing during the course of the study, and after study therapy has ended
- •Male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agreement to refrain from donating sperm
排除标准
- •Any other histological type of lymphoma according to WHO 2016 classification of lymphoid neoplasms, e.g., primary mediastinal (thymic) large B-cell lymphoma, Burkitt's lymphoma, BCL, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma (grey-zone lymphoma); primary effusion lymphoma; primary cutaneous DLBCL, leg type; primary DLBCL of the CNS; DLBCL arising from CLL or indolent lymphoma
- •History of prior non-hematologic malignancy except for the following:
- •Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening
- •Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer
- •Adequately treated carcinoma in situ without current evidence of disease
- •Any systemic anti-lymphoma and/or investigational therapy prior to the start of C1D1, except for permitted pre-phase treatment
- •Contraindication to any of the individual components of R-CHOP, including prior receipt of anthracyclines
- •Known CNS lymphoma involvement
- •Known active systemic bacterial, viral, fungal, or other infection at screening, including patients with suspected active or latent tuberculosis (as confirmed by a positive interferon-gamma release assay)
- •History or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that in the investigator's opinion would preclude participation in the study or compromise the patient's ability to give informed consent
研究组 & 干预措施
Tafasitamab plus lenalidomide in addition to R-CHOP
Patients will receive tafasitamab plus lenalidomide in addition to R-CHOP for six 21-day cycles:
Tafasitamab dose: 12 mg/kg body weight. Each 21-day cycle (cycles 1-6) will comprise of a tafasitamab IV infusion on Day 1, Day 8 and Day 15.
Lenalidomide dose: 25 mg as a starting dose per os (orally) once per day on Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Tafasitamab (Drug)
Tafasitamab plus lenalidomide in addition to R-CHOP
Patients will receive tafasitamab plus lenalidomide in addition to R-CHOP for six 21-day cycles:
Tafasitamab dose: 12 mg/kg body weight. Each 21-day cycle (cycles 1-6) will comprise of a tafasitamab IV infusion on Day 1, Day 8 and Day 15.
Lenalidomide dose: 25 mg as a starting dose per os (orally) once per day on Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Lenalidomide (Drug)
Tafasitamab plus lenalidomide in addition to R-CHOP
Patients will receive tafasitamab plus lenalidomide in addition to R-CHOP for six 21-day cycles:
Tafasitamab dose: 12 mg/kg body weight. Each 21-day cycle (cycles 1-6) will comprise of a tafasitamab IV infusion on Day 1, Day 8 and Day 15.
Lenalidomide dose: 25 mg as a starting dose per os (orally) once per day on Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Rituximab (Drug)
Tafasitamab plus lenalidomide in addition to R-CHOP
Patients will receive tafasitamab plus lenalidomide in addition to R-CHOP for six 21-day cycles:
Tafasitamab dose: 12 mg/kg body weight. Each 21-day cycle (cycles 1-6) will comprise of a tafasitamab IV infusion on Day 1, Day 8 and Day 15.
Lenalidomide dose: 25 mg as a starting dose per os (orally) once per day on Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Cyclophosphamide (Drug)
Tafasitamab plus lenalidomide in addition to R-CHOP
Patients will receive tafasitamab plus lenalidomide in addition to R-CHOP for six 21-day cycles:
Tafasitamab dose: 12 mg/kg body weight. Each 21-day cycle (cycles 1-6) will comprise of a tafasitamab IV infusion on Day 1, Day 8 and Day 15.
Lenalidomide dose: 25 mg as a starting dose per os (orally) once per day on Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Doxorubicin (Drug)
Tafasitamab plus lenalidomide in addition to R-CHOP
Patients will receive tafasitamab plus lenalidomide in addition to R-CHOP for six 21-day cycles:
Tafasitamab dose: 12 mg/kg body weight. Each 21-day cycle (cycles 1-6) will comprise of a tafasitamab IV infusion on Day 1, Day 8 and Day 15.
Lenalidomide dose: 25 mg as a starting dose per os (orally) once per day on Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Vincristine (Drug)
Tafasitamab plus lenalidomide in addition to R-CHOP
Patients will receive tafasitamab plus lenalidomide in addition to R-CHOP for six 21-day cycles:
Tafasitamab dose: 12 mg/kg body weight. Each 21-day cycle (cycles 1-6) will comprise of a tafasitamab IV infusion on Day 1, Day 8 and Day 15.
Lenalidomide dose: 25 mg as a starting dose per os (orally) once per day on Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Prednisone (Drug)
Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
Patients will receive tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP for six 21-day cycles:
Tafasitamab placebo: 0.9% saline solution Days 1, 8 and 15 of each 21-day cycle
Lenalidomide placebo: Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Rituximab (Drug)
Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
Patients will receive tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP for six 21-day cycles:
Tafasitamab placebo: 0.9% saline solution Days 1, 8 and 15 of each 21-day cycle
Lenalidomide placebo: Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Cyclophosphamide (Drug)
Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
Patients will receive tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP for six 21-day cycles:
Tafasitamab placebo: 0.9% saline solution Days 1, 8 and 15 of each 21-day cycle
Lenalidomide placebo: Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Doxorubicin (Drug)
Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
Patients will receive tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP for six 21-day cycles:
Tafasitamab placebo: 0.9% saline solution Days 1, 8 and 15 of each 21-day cycle
Lenalidomide placebo: Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Vincristine (Drug)
Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
Patients will receive tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP for six 21-day cycles:
Tafasitamab placebo: 0.9% saline solution Days 1, 8 and 15 of each 21-day cycle
Lenalidomide placebo: Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Prednisone (Drug)
Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
Patients will receive tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP for six 21-day cycles:
Tafasitamab placebo: 0.9% saline solution Days 1, 8 and 15 of each 21-day cycle
Lenalidomide placebo: Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Tafasitamab placebo (Drug)
Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
Patients will receive tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP for six 21-day cycles:
Tafasitamab placebo: 0.9% saline solution Days 1, 8 and 15 of each 21-day cycle
Lenalidomide placebo: Days 1-10 of each 21-day cycle
R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
干预措施: Lenalidomide placebo (Drug)
结局指标
主要结局
PFS-INV
时间窗: Time from date of randomization until Progressive Disease or death from any cause. In this trial, the primary endpoint is PFS as assessed by the investigator (up to 43 months)
Progression-Free Survival as assessed by the investigator using the Lugano Response Criteria for Malignant Lymphoma
次要结局
- ORR as per INV at EOT(6 ± 2 weeks after End of Treatment)
- Metabolic PET-negative CR-rate at EOT by INV(End of treatment, 4-8 weeks after last dose)
- EFS-INV(From randomization until the first occurrence of disease progression or relapse as assessed by the INV using, start of new anti-lymphoma treatment or death from any cause, whichever occurs first (up to 43 months))
- OS(From randomization until the date of death from any cause (up to 62 months))
- Metabolic PET-negative CR-rate at EOT by BIRC(End of treatment, 4-8 weeks after last dose)
- Time to next anti-lymphoma treatment (TTNT)(From randomization date to start of next anti-lymphoma therapy (for any reason including disease progression, treatment toxicity, and patient preference) or death due to any cause, whatever comes first (up to 43 months))
- OS at 3 years(36 months after randomization)
- PFS at 3 years(36 months after randomization)
- Duration of Complete Response (CR) as assessed by the investigator(From the date of the first occurrence of a documented CR, to the date of progression, relapse, or death from any cause, whichever is earlier (up to 43 months))
- EFS at 3 years(36 months after randomization)