NCT04984837进行中（未招募）2 期
A Randomized Non Comparative Phase II Study of Lacutamab With GemOx Versus GemOx Alone in Relapsed/Refractory Patients With Peripheral T-cell Lymphoma
The Lymphoma Academic Research Organisation182 个研究点 分布在 3 个国家目标入组 49 人开始时间: 2021年10月5日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 49
- 试验地点
- 182
- 主要终点
- median modified progression-free survival (mPFS) - CT-based
研究概览
简要总结
This is an open-label multicenter randomized non comparative phase II study to evaluate the safety and efficacy of the monoclonal anti-KIR3DL2 antibody Lacutamab in patients with Refractory/Relapsing (R/R) KIR3DL2 positive Peripheral T Cell Lymphoma (PTCL) : Not Other Specified (NOS), PTCL-TFH (including Angioimmunoblastic T-cell Lymphoma (AITL), Follicular T-cell lymphoma, Nodal peripheral T-cell lymphoma with TFH phenotype), Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma (ATL), Hepatosplenic T-cell lymphoma (HSTL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL), NK-T cell lymphoma (NKT) and Aggressive NK-cell leukemia (ANKL).
The design is non comparative meaning that non comparison between arms will be performed as the control arm will ensure that the assumptions used for sample size calculation are verified. For that reason, randomization is unbalanced in favor of the experimental arm (2:1).
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
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
- •1. KIR3DL2-positive with at least 1% of tumour cells positivity, before randomization, based on central evaluation by immunohistochemistry (IHC)
- •Patients with histologically documented PTCL:
- •Biopsy-proven treated PTCL defined by the WHO 2016 criteria (the biopsy at relapse is recommended but not mandatory):
- •PTCL-TFH (AITL, Follicular T-cell lymphoma, Nodal peripheral T-cell lymphoma with TFH phenotype)
- •ATL: acute- or lymphoma-type
- •For patients with ALCL: previously treated with brentuximab vedotin
- •Relapsed/refractory PTCL after at least one previous line of systemic based regimen of chemotherapy (no mandatory latency after the previous treatment)
- •With a maximum of 2 prior lines of systemic therapies, including autologous stem cell transplantation (ASCT is authorized in first and second line and is not counted as a unique line, even if associated to a systemic therapy)
- •Bi-dimensionally measurable disease defined by at least one single node or tumor lesion ≥ 1.5 cm assessed by CT scan
- •Signed written screening informed consent prior to KIR3DL2 screening
- •Signed written study informed consent prior to randomization
- •Aged 18 years or more with no upper age limit, at randomization
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3 prior to prephase treatment (if applicable), and 0 to 2 prior randomization
- •Minimum life expectancy of 3 months
- •Females of childbearing potential (FCBP) must agree to use highly effective contraceptive method* from C1D1, during the entire study period, during dose interruptions, and for 9 months after the last study treatments
- •FCBP must have a negative serum or urinary pregnancy test within 28 days prior C1D1
- •Male patients and their partner (FCBP) must agree to use two reliable forms of contraception (condom for males and hormonal method for partners) from C1D1, during the entire study period, during dose interruptions, and for 9 months after the last study treatments
排除标准
- •1. Patients with active COVID-19 infection (last positive PCR < 2 weeks before randomization)
- •Patients taking immunotherapy or chemotherapy, except short-term corticosteroids in monotherapy at a cumulated dose equivalent of prednisone ≤ 1mg/kg/day, during 7 consecutive days, within 3 weeks prior to first administration of study drug (C1D1); or prephase treatment given at investigator's discretion before randomization and for maximum 3 weeks (glucocorticosteroids, vepesid (VP16), cyclophosphamide, vincristine and prednisone (COP))
- •Previous treatment by Gemcitabine or Oxaliplatin
- •Use of any experimental anti-cancer drug therapy within 6 weeks before randomization
- •Contraindication to any drug contained in the study treatment regimen
- •Previous allogenic hematopoietic cell transplantation
- •Positive test results for HIV and Hepatitis C Virus (HCV) (Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation)
- •Known active hepatitis B (positive Ag HBs) (if latent Hepatitis B Virus (HBV) (positive anti-HBc), patients have to be treated with Entecavir (Baraclude ®) and HBV PCR should be performed every month to allow antiviral strategy adaptation)
- •Central nervous system or meningeal involvement by lymphoma
- •Any of the following laboratory abnormalities prior randomization:
- •Absolute neutrophil count (ANC) < 1 G/L, unless neutropenia is related to PTCL
- •Platelet count < 75 G/L, unless thrombopenia is related to PTCL
- •Alkaline Phosphatases > 2.5 x upper limit of normal (ULN)
- •Serum Glutamoyl-oxaloacetate Transferase (SGOT) /Alanine aminotransferase (AST) or Serum Glutamate Pyruvate Transaminase (SGPT)/Alanine aminotransferase (ALT) > 2.5 x ULN
- •Bilirubin > 1.5 x ULN, unless SGOT/AST and SGPT/ALT > 2.5 x ULN or bilirubin elevated due to PTCL or hemolysis
- •Calculated creatinine clearance (MDRD or Cockcroft) < 40 mL/min
- •Any significant cardiovascular impairment: New York Heart Association (NYHA) Class III or IV cardiac disease, uncontrolled high blood pressure, unstable angina, myocardial infarction or stroke within the last 6 months from randomization, and cardiac arrhythmia within the last 3 months from randomization
- •Uncontrolled clinically significant intercurrent illness including, but not limited to, diabetes, ongoing active infections. Patients receiving antibiotics for infections that are under control may be included in the study
- •Concurrent malignancy or prior history of malignancies other than lymphoma unless the subject has been free of disease for ≥ 2 years, except early stage cutaneous squamous or basal cell carcinoma, localized prostate cancer, or cervical intraepithelial neoplasia
- •Major surgery within 4 weeks before randomization
- •Pregnant or lactating females
研究组 & 干预措施
Lacutamab
Experimental
Lacutamab 750 mg/IV + GEmOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase Lacutamab 750 mg/IV for a maximum of 20 additional cycles of 4 weeks during the maintenance phase
干预措施: Gemcitabine (Drug)
Lacutamab
Experimental
Lacutamab 750 mg/IV + GEmOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase Lacutamab 750 mg/IV for a maximum of 20 additional cycles of 4 weeks during the maintenance phase
干预措施: Lacutamab (Drug)
Lacutamab
Experimental
Lacutamab 750 mg/IV + GEmOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase Lacutamab 750 mg/IV for a maximum of 20 additional cycles of 4 weeks during the maintenance phase
干预措施: Oxaliplatine (Drug)
Standard of care
Active Comparator
GemOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase
干预措施: Oxaliplatine (Drug)
Standard of care
Active Comparator
GemOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase
干预措施: Gemcitabine (Drug)
结局指标
主要结局
median modified progression-free survival (mPFS) - CT-based
时间窗: 5,5 years.
time from randomization until one of the following events occurs, whichever comes first: 1. Disease progression (PD) 2. Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations (HCT)) 3. Relapse after achievement of CR 4. Death due to any cause. PD and relapse will be evaluated according to Lugano 2014 criteria (CT-based).
次要结局
- complete response rate (CRR) Lugano 2014 criteria (CT-based)(5,5 years.)
- Number of Adverse Events(5,5 years.)
- complete response rate (CRR) Lugano 2014 criteria (PET-based)(5,5 years.)
- overall survival (OS)(5,5 years.)
- rate of patients proceeding to allogenic stem cell transplantation(5,5 years.)
- Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)(29 months (29 cycles))
- overall response rate (ORR) Lugano 2014 criteria (CT-based)(5,5 years.)
- Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)(29 months (29 cycles))
- Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx(29 months)
- median modified progression-free survival (mPFS) - PET-based(5,5 years.)
- overall response rate (ORR) Lugano 2014 criteria (PET-based)(5,5 years.)
- response rate assessed by Deauville criteria(5,5 years.)
- duration of response (DOR),(5,5 years.)
- Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)(1 month (1 cycle))
- Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)(1 month (1 cycle))
- Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)(2 months (2 cycles))
- Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)(2 months (2 cycles))
- Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)(3 months (3 cycles))
- Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)(3 months (3 cycles))
- Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)(15 months (15 cycles))
- Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)(15 months (15 cycles))
- Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)(26 months (26 cycles))
- Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)(26 months (26 cycles))
- Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx(1 month (1 cycle))
- Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx(2 months (2 cycles))
- Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx(3 months (3 cycles))
- Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx(7 months (7 cycles))
- Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx(9 months (9 cycles))
- Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx(15 months (15 cycles))
- Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx(26 months)
- Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)(7 months (7 cycles))
- Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)(7 months (7 cycles))
- Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)(9 months (9 cycles))
- Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)(9 months (9 cycles))
研究者
研究点 (182)
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