Consolidation With ADCT-402 (Loncastuximab Tesirine) After a Short Course of Immunochemotherapy: a Phase II Study in BTKi-treated (or BTKi Intolerant) Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) Patients
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 49
- 试验地点
- 40
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a prospective, phase 2, multicenter, open-label, single-arm study. Primary objective is to assess the efficacy of loncastuximab tesirine given as consolidation therapy after salvage immunochemotherapy in BTKi (Bruton Tyrosine Kinase inhibitors) -treated (or BTKi intolerant) R/R (Relapse or Refractory) MCL (Mantle Cell Lymphoma) patients. The sponsor of this clinical trial is Fondazione Italiana Linfomi - ETS (FIL ETS).
详细描述
This is a Phase 2, multicenter, open-label, single-arm study of the efficacy and safety of loncastuximab tesirine given as consolidation therapy after salvage immunochemotherapy in BTKi-treated (or BTKi intolerant) R/R MCL patients.
Primary Objective:
- To assess the efficacy of a consolidation with loncastuximab tesirine following salvage immunochemotherapy (2 courses of Rituximab-Bendamustine-Cytarabine, R-BAC) in Bruton Tyrosine Kinase inhibitors (BTKi) treated (or BTKi intolerant) relapsed/refractory (R/R) Mantle Cell Lymphomas (MCL).
Secondary Objectives:
- To evaluate the safety profile of loncastuximab tesirine consolidation.
- To assess the rate of Minimal Residual Disease (MRD) negativity after loncastuximab tesirine consolidation.
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically documented diagnosis of MCL as defined in the 2017 edition of the World Health Organization (WHO) classification
- •Age ≥ 18 and < 85 years
- •Relapsed/Refractory disease after one, two, three or four lines of treatment
- •Bendamustine-naive or relapsed after at least one year after the last cycle of a bendamustine-containing regimen
- •Previous treatment with BTKi (Bruton Tyrosine Kinase inhibitors) monotherapy or BTKi containing regimens with R/R disease; and/or patients who discontinued BTKi monotherapy or BTKi containing regimens for adverse events and have active disease necessitating treatment.
- •Previous treatment with any anti-CD19 agents is allowed (included CAR-T treatment) If previous anti-CD19 treatment has occurred, tissue CD19 expression must be assessed by histology or flow cytometry
- •Venetoclax treated patients are allowed.
- •Stem cell transplant eligible patients are allowed.
- •Measurable nodal or extranodal disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions. Note: Patients with bone marrow involvement only are eligible. In case of bone marrow infiltration only, bone marrow aspiration and biopsy are mandatory for all staging evaluations
- •ECOG (Eastern Cooperative Oncology Group)/WHO (World Health Organization) performance status ≤ 2 (unless MCL-related)
- •The following laboratory values at screening (unless due to bone marrow involvement by lymphoma):
- •Absolute Neutrophil count (ANC) > 1.0×109/L
- •Platelet count ≥ 75.000/mm3
- •Creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula)
- •Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN (upper limit of normal)
- •Bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non- hepatic origin)
- •Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures.
- •Subject must be able to adhere to the study visit schedule and other protocol requirements.
- •Life expectancy ≥ 3 months.
- •Women of childbearing potential (WOCBP) and men must agree to use effective contraception if sexually active.This applies for the time period between signing of the informed consent form and at least 10 months after last loncastuximab tesirine (ADCT-402) dose. Men with female partners who are of childbearing potential must agree to use effective contraception if sexually active. This applies for the time period between signing of the informed consent form and at least 7 months after last loncastuximab tesirine (ADCT-402) dose.
排除标准
- •Subjects who have received a bendamustine containing regimen and relapsed less than one year after the end of treatment.
- •Known history of hypersensitivity to human antibodies.
- •Allogenic stem cell transplant within 6 months prior to start of first study drug.
- •Allogenic stem cell transplant with active / uncontrolled graft-versus-host disease.
- •Previous treatment with CD19 targeting agents.
- •More than four lines of previous treatment (autologous stem cell transplant performed as part of consolidation to a previous line of therapy should not be considered as a line of therapy).
- •Active second malignancy in the last three years other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or any other tumor that the Sponsor and Coordinating Investigator agree and document should not be considered preclusive to participate in the study.
- •Major surgery or any anticancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to start of study drug (R-BAC). A shorter interval in special settings must be approved by the Sponsor and/or Investigator.
- •Cardiovascular disease (NYHA, New York Heart Association, class ≥2).
- •Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent.
- •Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
- •Uncontrolled and/or active systemic infection (viral including COVID 19, bacterial or fungal);
- •Chronic or acute hepatitis B (HBV) or hepatitis C (HCV) requiring treatment. Note:
- •subjects with serologic evidence of prior vaccination to HBV (i.e., HBsAg negative, HBsAb positive and HBcAb negative) or positive HBcAb from previous infection or intravenous immunoglobulins (IVIG) may participate; inactive carriers (HBsAg positive with undetectable HBV DNA) are eligible. Patients with presence of HCV antibody are eligible only if PCR results (polimerase chain reaction) negative for HCV RNA.
- •HIV seropositivity.
- •Lymphoma with active CNS (central nervous system) involvement at the time of screening, including leptomeningeal disease.
- •Congenital long QT syndrome or a corrected QTcF interval of >480 msec at screening (unless secondary to pacemaker or bundle branch block).
- •Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the patient inappropriate for study participation or put the patient at risk.
- •If female, the patient is pregnant or breast-feeding.
研究组 & 干预措施
Consolidation with ADCT-402 (loncastuximab tesirine) after a short course of immunochemotherapy
R/R MCL after one, two, three or four lines of treatment including BTKi treatment (or BTKi intolerant), with complete response (CR) or partial response (PR) or with stable disease (SD) after salvage immunochemotherapy (R-BAC, Rituximab - Bendamustine, Ara-C x 2 cycles) will undergo consolidation with loncastuximab tesirine. A patient with CR, PR or SD after one R-BAC course, which is unable to undergo a second course due to toxicity to chemotherapy, can be considered to proceed for consolidation.
干预措施: Consolidation with ADCT-402 (loncastuximab tesirine) after salvage immunochemotherapy at standard dose (R-BAC, Rituximab - Bendamustine, Ara-C)) (Drug)
Consolidation with ADCT-402 (loncastuximab tesirine) after a short course of immunochemotherapy
R/R MCL after one, two, three or four lines of treatment including BTKi treatment (or BTKi intolerant), with complete response (CR) or partial response (PR) or with stable disease (SD) after salvage immunochemotherapy (R-BAC, Rituximab - Bendamustine, Ara-C x 2 cycles) will undergo consolidation with loncastuximab tesirine. A patient with CR, PR or SD after one R-BAC course, which is unable to undergo a second course due to toxicity to chemotherapy, can be considered to proceed for consolidation.
干预措施: Consolidation with ADCT-402 (loncastuximab tesirine) after salvage immunochemotherapy at reduced dose (R-BAC, Rituximab - Bendamustine, Ara-C) (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: The primary endpoint will be assessed from the beginning of the study up to 36 months.
The length of time during and after the treatment that patients live with the disease, but it does not get worse. Progression-Free Survival (PFS) will be defined from the date of enrollment and the first documentation of recurrence, progression or death from any cause. Responding patients and patients who are lost to follow up will be censored at their last assessment date. PFS will be assessed on an ITT (Intention to Treat) basis.
次要结局
- Overall Survival (OS)(The endpoint will be assessed from the beginning of the study up to 36 months)
- Overall Response Rate (ORR)(The endpoint will be assessed from the beginning of the study therapy up to 6 months)
- Rate of Adverse Events(The endpoint will be assessed from the beginning of the study therapy up to 36 months)
- Duration of Response (DOR)(The endpoint will be assessed from the beginning of the study therapy up to 36 months)
- Event-Free Survival (EFS)(The endpoint will be assessed from the beginning of the study therapy up to 36 months)
- MRD (Minimal Residual Disease) negativity rate(The endpoint will be assessed from the beginning of the study therapy up to 18 months)
- Rate of conversion from partial response (PR) to complete response (CR)(The endpoint will be assessed from the beginning of the study therapy up to 6 months)
- Rate of conversion from stable disease (SD) to complete response (CR) and partial response (PR)(The endpoint will be assessed from the beginning of the study therapy up to 6 months)