A Study to Evaluate Glofitamab Monotherapy and Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma

Официальное название

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

Обзор

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).

Вмешательства

• Препарат Obinutuzumab
  Participants will receive intravenous (IV) obinutuzumab pretreatment on Days 1 and 2 of Cycle 1 (Cycle length = 21 days)
• Препарат Glofitamab
  Arm A: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of Cycles 2 and 3 Arm B: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of each cycle thereafter (Cycle length = 21 days)
• Препарат Rituximab
  Participants will receive IV rituximab on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)
• Препарат Ifosfamide
  Participants will receive IV ifosfamide on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)
• Препарат Carboplatin
  Participants will receive IV carboplatin on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)
• Препарат Etoposide
  Participants will receive IV etoposide on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)
• Препарат Tocilizumab
  Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events

Первичные конечные точки

• 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) [Срок оценки: Up to 3 treatment cycles (cycle length = 21 days)]
• Percentage of participants with adverse events (AEs) (Arm A) [Срок оценки: Approximately 3 years]
• Serum concentration of glofitamab in combination with R-ICE chemoimmunotherapy (Arm A) [Срок оценки: Up to 3 treatment cycles (cycle length = 21 days)]
• Serum concentration of glofitamab monotherapy (Arm B) [Срок оценки: Up to 12 treatment cycles (Arm B) (cycle length = 21 days)]

Вторичные конечные точки (11)

• Objective response rate (ORR) (Arms A and B) [Срок оценки: Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)]
• Duration of complete response (DOCR) (Arm A) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: Up to 3 treatment cycles (cycle length = 21 days)]
• Duration of response (DOR) (Arm B) [Срок оценки: 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) [Срок оценки: Approximately 3 years]
• Serum concentration of obinutuzumab (Arms A and B) [Срок оценки: Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)]
• Serum concentration of rituximab (Arm A) [Срок оценки: Up to 3 treatment cycles (cycle length = 21 days)]
• Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B) [Срок оценки: Up to 3 treatment cycles (cycle length = 21 days)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 10 центров

• Children's Hospital of Alabama — Birmingham
• UCSF Benioff Children's Hospital Oakland — Oakland
• Kaiser Permanente Oakland Medical Center — Oakland
• Kaiser Permanente - Roseville — Roseville
• Kaiser Permanente - Santa Clara — Santa Clara
• Johns Hopkins University — Baltimore
• Dana-Farber Cancer Institute — Boston
• Childrens Mercy Hosp & Clinics — Kansas City
• … и ещё 2 центра

Китай · 3 центра

• West China Second University Hospital — Чэнду
• Sun Yet-sen University Cancer Center — Гуанчжоу
• Guangxi Cancer Hospital of Guangxi Medical University — Nanning

Австралия · 2 центра

• Queensland Children?s Hospital — South Brisbane
• Perth Children's Hospital — Nedlands

Бразилия · 2 центра

• Hospital Erasto Gaertner — Curitiba
• Graacc-Grupo de Apoio ao adolescente e a crianca com cancer — São Paulo

Франция · 2 центра

• Hôpital Pellegrin — Bordeaux
• Gustave Roussy — Villejuif

Италия · 2 центра

• IRCCS Ospedale Pediatrico Bambino Gesù — Rome
• Ospedaliera Ospedale Infantile Regina Margherita — Turin

South Korea · 2 центра

• Seoul National University Hospital- Pediatric Site — Seoul
• Asan Medical Center — Seoul

Испания · 2 центра

• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Infantil Universitario Niño Jesus — Madrid

Чехия · 1 центр

• Fakultni nemocnice v Motole;Klinika detske hematologie a onkologie — Prague

Дания · 1 центр

• Rigshospitalet — København Ø

Германия · 1 центр

• Universitaetsklinikum Muenster — Münster

Венгрия · 1 центр

• Semmelweis Egyetem II. sz. Gyermekgyogyaszati Klinika — Budapest

Польша · 1 центр

• Ponadregionalne Centrum Onkologii Dzieci?cej ,,Przyladek Nadziei?;Klinika Transplantacji S — Wroclaw

Идентификаторы

NCT: NCT05533775 · CO43810

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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