2022-501601-12-00已完成2 期
A Phase 2 Open-label Study of Loncastuximab Tesirine in Combination with Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Patients with Diffuse Large B-cell Lymphoma (DLBCL) (LOTIS-9)
ADC Therapeutics S.A., ADC Therapeutics S.A.12 个研究点 分布在 2 个国家目标入组 28 人开始时间: 2023年2月27日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 12
- 主要终点
- Cohort A • CR rate defined as proportion of patients with a BOR of CR according to the 2014 Lugano Classification criteria
研究概览
简要总结
Cohort A To assess the efficacy of a response-adapted treatment of Lonca-R in unfit patients with previously untreated DLBCL, or HGBCL, or Grade 3b FL Cohort B To assess the tolerability and efficacy of a response-adapted treatment of Lonca-R in frail patients or patients with cardiac comorbidities with previously untreated DLBCL, or HGBCL, or Grade 3b FL, who are ineligible for standard R-mini-CHOP
研究设计
- 分配方式
- Not Applicable
- 主要目的
- A Phase 2 Open-label Study Of Loncastuximab Tesirine In Combination With Rituximab (lonca-r) In Prev
- 盲法
- None
入排标准
- 年龄范围
- 65 years 至 65+ years（65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Male or female
- •Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization (WHO) classification (including patients with DLBCL transformed from indolent lymphoma), or high-grade B cell lymphoma (HGBCL), or Grade 3b follicular lymphoma (FL).
- •Measurable disease as defined by the 2014 Lugano Classification
- •Stages I-IV
- •ECOG PS 0-2; ECOG PS 3 allowed if decline in status is deemed related to lymphoma & felt to be potentially reversible by the treating physician
- •Adequate organ function as defined by screening laboratory values within the following parameters: a. Absolute neutrophil count (ANC) ≥ 1.0 × 10^3/µL (off growth factors at least 72 hours) b. Platelet count ≥ 75 × 10^3/µL without transfusion in the past 7 days c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤ 2.5 × the upper limit of normal (ULN) d. Total bilirubin ≤ 1.5 × ULN (patients with known Gilbert’s syndrome may have a total bilirubin up to ≤ 3 × ULN) e. Calculated creatinine clearance > 30 mL/min by the Cockcroft and Gault equation
- •Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 12 months after the last dose of study treatment. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of the first dose until at least 7 months after the patient receives her/his last dose of study treatment
- •Inclusion Criteria specific for Cohort A: Unfit as defined by the sGA (includes all of the following): a. Aged ≥ 80 years b. ADL score of 6 c. IADL score of 8 d. CIRS-G: no score of 3-4 and < 5 scores of 2
- •Inclusion Criteria specific for Cohort B: Frail as defined by the sGA: a. Aged ≥ 80 years b. ADL score of < 6 and/or c. IADL score of < 8 and/or d. CIRS-G ≥ 1 score of 3-4 and/or ≥ 5 scores of 2 OR Aged ≥ 65 - <80 with at least one of the following cardiac comorbidities that make anthracycline-containing regimens inadvisable as determined by the investigator. a. Left ventricular ejection fraction (LVEF) ≥ 30 to < 50% b. History of myocardial infarction within 6 months prior to screening c. Ischemic heart disease d. History of stroke within 12 months prior to screening
排除标准
- •Known history of hypersensitivity to or positive serum human anti-drug antibody to a CD19 antibody
- •Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
- •Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drug (Cycle 1 Day 1 [C1D1]), except shorter if approved by the Sponsor
- •Use of any other experimental medication within 14 days prior to start of study drug (C1D1)
- •Received live vaccine within 4 weeks of C1D1
- •Congenital long QT syndrome or a corrected QTcF interval of > 480 ms at screening (unless secondary to pacemaker or bundle branch block)
- •Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor’s Medical monitor and Investigator agree, and document should not be exclusionary
- •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
- •Previous therapy for DLBCL, HGBCL, Grade 3b FL (with exception of corticosteroid course for symptom management of less than 14 days)
- •Previous therapy with loncastuximab tesirine and rituximab for any indication
- •Known history of hypersensitivity to any component of study treatment (loncastuximab tesirine and rituximab)
- •Human immunodeficiency virus (HIV) seropositive with any of the following: a. CD4+ T-cell (CD4+) counts < 350 cells/µL b. Acquired immunodeficiency syndrome (AIDS) – defining opportunistic infection within 12 months prior to screening c. Not on anti-retroviral therapy, or on anti-retroviral therapy for < 4 weeks at the time of screening d. HIV viral load ≥ 400 copies/mL
- •Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load
- •Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load
- •History of Stevens-Johnson syndrome or toxic epidermal necrolysis
- •Lymphoma with active central nervous system involvement at the time of screening, including leptomeningeal disease
结局指标
主要结局
Cohort A • CR rate defined as proportion of patients with a BOR of CR according to the 2014 Lugano Classification criteria
Cohort A • CR rate defined as proportion of patients with a BOR of CR according to the 2014 Lugano Classification criteria
Cohort B • CR rate defined as proportion of patients with a BOR of CR according to the 2014 Lugano Classification criteria
Cohort B • CR rate defined as proportion of patients with a BOR of CR according to the 2014 Lugano Classification criteria
Cohort B • Tolerability as defined by the percentage of patients completing a total of 4 cycles of therapy divided by the total number of patients.
Cohort B • Tolerability as defined by the percentage of patients completing a total of 4 cycles of therapy divided by the total number of patients.
次要结局
- ORR according to the 2014 Lugano Classification defined as the proportion of patients with a BOR of CR or PR.
- 2 year PFS, defined as the proportion of patients that are PFS event-free at 2 years
- 3 year overall survival (3-yr OS), defined as the proportion of patients that are OS event-free at 3 years.
- Duration of response (DoR) defined as the time from the first documentation of tumor response (CR or PR) to disease progression or death
- Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)
- Changes from baseline in safety laboratory variables, vital signs, physical examinations, Eastern Cooperative Oncology Group scale of performance status (ECOG PS)
- Concentrations and PK parameters of loncastuximab tesirine pyrrolobenzodiazepine (PBD)-conjugated antibody, total antibody, and SG3199 unconjugated warhead
- Frequency of confirmed positive anti-drug antibody (ADA) responses, their associated titers and, if applicable, neutralizing activity to loncastuximab tesirine after treatment with loncastuximab tesirine when given in combination with rituximab
- Changes in patient-reported outcomes (e.g., symptoms, functions, and overall health status) from baseline as evaluated by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)
研究者
Clinical Operations
Scientific
ADC Therapeutics S.A.
研究点 (12)
Loading locations...
相似试验
已完成
3 期
A Study of Subcutaneous Risankizumab Injection for Pediatric Participants With Moderate to Severe Plaque Psoriasis to Assess Change in Disease Symptoms (OptIMMize-1)2023-504156-10-00Abbvie Deutschland GmbH & Co. KG72
招募中
2 期
Sac-TMT Plus KL-A167 in PD-L1+, HR+/HER2- Metastatic Breast Cancer After CDK4/6 InhibitorsBreast CancerNCT07258108Sun Yat-sen University35
招募中
2 期
Obinutuzumab, Zanubrutinib, and Lenalidomide in First-line Treatment of Mantle Cell LymphomaMantle Cell LymphomaNCT07261163Institute of Hematology & Blood Diseases Hospital, China37
招募中
2 期
Evaluation of the efficacy and safety of Rituximab in patients with Amyotrophic Lateral Sclerosis (ALS)2022-502743-35-00Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.52
招募中
2 期
A Study to understand the Effectiveness, Safety, and what the body does to Mosunetuzumab in participants with Systemic Lupus Erythematosus with or without Active Lupus Nephritis2024-519930-22-00F. Hoffmann-La Roche AG5