NCT05533775招募中1 期
A Phase I/II, Open-Label, Single-Arm, Two-Part Trial to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of Glofitamab in Monotherapy and in Combination With Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 65
- 试验地点
- 30
- 主要终点
- Achievement of a complete response (CR) as determined by the investigator according to the International Pediatric NHL Response Criteria for pediatric participants and Lugano Classification for young adult participants (Arm A)
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of glofitamab, as monotherapy and in combination with a standard chemoimmunotherapy regimen: rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in pediatric and young adult participants with relapsed and refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 6 months to < 18 years at the time of signing Informed Consent for Cohort A Part 1 and Cohort B of the study, and age 6 months to < 30 years old at the time of signing Informed Consent for Cohort A Part 2 of the study
- •Histologically re-confirmed diagnosis, via tissue biopsy, or bone marrow aspirate, pleural effusion, or ascites, prior to study entry of aggressive mature B-NHL that expresses CD20 (reconfirmed by IHC or flow cytometry if IHC is not possible), including BL, BAL (mature B-cell leukemia FAB L3), DLBCL, and PMBCL, at the time of first R/R disease for Cohort A and second or greater R/R disease for Cohort B
- •Refractory or relapsed disease (i.e., prior treatment was ineffective or intolerable) following first-line standard-of-care chemoimmunotherapy for Cohort A and following at least two prior systemic chemoimmunotherapy regimens and who have exhausted all available established therapies for Cohort B
- •Measurable disease, defined as: At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension; or percentage of bone marrow involvement with lymphoma cells defined by cytomorphological analysis of bone marrow aspirates
- •Adequate performance status, as assessed according to the Lansky or Karnofsky Performance Status scales: Participants < 16 years old: Lansky Performance Status ≥ 50%; Participants ≥ 16 years old: Karnofsky Performance Status ≥ 50%
- •Adequate bone marrow, liver, and renal function
- •Negative test results for acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV)
- •Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count ≥200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months
- •Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment
- •Participants and/or caregivers who are willing and able to complete clinical outcome assessments throughout the study using either paper or interviewer methods
排除标准
- •Isolated CNS disease of mature B-NHL without systemic involvement, and primary CNS lymphoma
- •Receipt of glofitamab prior to study enrollment
- •Ongoing adverse events from prior anti-cancer therapy that were not resolved to Grade ≤ 1 (exceptions: alopecia, Grade 2 peripheral neuropathy)
- •Grade ≥ 3 adverse events, with the exception of Grade 3 endocrinopathy managed with replacement therapy
- •Participants with active infections which are not resolved prior to Day 1 of Cycle 1
- •Prior solid organ transplantation
- •Known or suspected history of hemophagocytic lymphohistiocytosis (HLH), or chronic active Epstein-Barr viral infection (CAEBV)
- •Active autoimmune disease requiring treatment
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products, except if the participant was able to safely receive it after initial administration (consider consultation with Medical Monitor)
- •History of confirmed progressive multifocal leukoencephalopathy
- •Current or past history of uncontrolled non-malignant CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
- •Evidence of significant and uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
- •Major surgery or significant traumatic injury < 28 days prior to the obinutuzumab pretreatment infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
- •Administration of a live, attenuated vaccine within 4 weeks before the start of study treatment (obinutuzumab pretreatment) or at any time during the study treatment period and within 12 months after end of study treatment
- •Participants with any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
研究组 & 干预措施
Arm A
Experimental
Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).
干预措施: Carboplatin (Drug)
Arm A
Experimental
Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).
干预措施: Rituximab (Drug)
Arm A
Experimental
Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).
干预措施: Etoposide (Drug)
Arm B
Experimental
Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days).
干预措施: Glofitamab (Drug)
Arm A
Experimental
Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).
干预措施: Ifosfamide (Drug)
Arm A
Experimental
Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).
干预措施: Obinutuzumab (Drug)
Arm A
Experimental
Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).
干预措施: Glofitamab (Drug)
Arm A
Experimental
Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).
干预措施: Tocilizumab (Drug)
Arm B
Experimental
Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days).
干预措施: Obinutuzumab (Drug)
Arm B
Experimental
Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days).
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Achievement of a complete response (CR) as determined by the investigator according to the International Pediatric NHL Response Criteria for pediatric participants and Lugano Classification for young adult participants (Arm A)
时间窗: Up to 3 treatment cycles (cycle length = 21 days)
Percentage of participants with adverse events (AEs) (Arm A)
时间窗: Approximately 3 years
Serum concentration of glofitamab in combination with R-ICE chemoimmunotherapy (Arm A)
时间窗: Up to 3 treatment cycles (cycle length = 21 days)
Serum concentration of glofitamab monotherapy (Arm B)
时间窗: Up to 12 treatment cycles (Arm B) (cycle length = 21 days)
次要结局
- Objective response rate (ORR) (Arms A and B)(Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days))
- Duration of complete response (DOCR) (Arm A)(From the first occurrence of a documented complete response (CR) to documented disease progression or death from any cause (whichever occurs first) (approximately 3 years))
- Progression-free survival (PFS) (Arm A)(From enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) (approximately 3 years))
- Event-free survival (EFS) (Arm A)(From enrollment to the first occurrence of disease progression, death from any cause, or start of new anti-lymphoma therapy (not including planned hematopoietic stem cell transplantation (HSCT)) (approximately 3 years))
- Percentage of participants who proceed to HSCT after up to three cycles of treatment (Arm A)(Up to 3 treatment cycles (cycle length = 21 days))
- Duration of response (DOR) (Arm B)(From the first occurrence of a documented CR or partial response (PR) until documented disease progression or death from any cause, whichever occurs first (approximately 4 years))
- Percentage of participants with AEs (arm B)(Approximately 3 years)
- Serum concentration of obinutuzumab (Arms A and B)(Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days))
- Serum concentration of rituximab (Arm A)(Up to 3 treatment cycles (cycle length = 21 days))
- Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B)(Up to 3 treatment cycles (cycle length = 21 days))
- Objective response rate (ORR) (Arms A and B)(Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days))
- Duration of complete response (DOCR) (Arm A)(From the first occurrence of a documented complete response (CR) to documented disease progression or death from any cause (whichever occurs first) (approximately 3 years))
- Progression-free survival (PFS) (Arm A)(From enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) (approximately 3 years))
- Event-free survival (EFS) (Arm A)(From enrollment to the first occurrence of disease progression, death from any cause, or start of new anti-lymphoma therapy (not including planned hematopoietic stem cell transplantation (HSCT)) (approximately 3 years))
- Overall survival (OS) (Arms A and B)(From enrollment to the date of death from any cause (Arm A = approximately 3 years, Arm B = approximately 4 years))
- Percentage of participants who proceed to HSCT after up to three cycles of treatment (Arm A)(Up to 3 treatment cycles (cycle length = 21 days))
- Duration of response (DOR) (Arm B)(From the first occurrence of a documented CR or partial response (PR) until documented disease progression or death from any cause, whichever occurs first (approximately 4 years))
- Percentage of participants with AEs (arm B)(Approximately 3 years)
- Serum concentration of obinutuzumab (Arms A and B)(Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days))
- Serum concentration of rituximab (Arm A)(Up to 3 treatment cycles (cycle length = 21 days))
- Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B)(Up to 3 treatment cycles (cycle length = 21 days))
研究者
研究点 (30)
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