A Study to Evaluate the Optimization of the Cytokine Release Syndrome Profile for Glofitamab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed/Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma

Официальное название

A Phase II, Open-Label, Multicenter Study to Evaluate the Optimization of the Cytokine Release Syndrome Profile for Glofitamab in Combination With Gemcitabine Plus Oxaliplatin in Patients With Relapsed/Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma

Обзор

This Phase II trial evaluates the optimization of the cytokine release syndrome (CRS) profile for glofitamab in combination with gemcitabine and oxaliplatin (Glofit-GemOx) in participants with relapsed or refractory aggressive B-cell Non-Hodgkin's lymphoma. The study utilizes an optimized steroid premedication regimen and monitoring schedule specifically designed to enable the administration of the treatment regimen in an outpatient setting.

Вмешательства

• Препарат Obinutuzumab
  Participants will receive intravenous (IV) obinutuzumab 7 days prior to the first dose of glofitamab.
• Препарат Glofitamab
  Participants will receive IV glofitamab, both in combination with gemcitabine and oxaliplatin and as monotherapy, for up to 12 cycles (cycle length = 21 days).
• Препарат Gemcitabine
  Participants will receive IV gemcitabine in combination with glofitamab and oxaliplatin for up to 8 cycles (cycles length = 21 days).
• Препарат Oxaliplatin
  Participants will receive IV oxaliplatin in combination with glofitamab and gemcitabine for up to 8 cycles (cycle length = 21 days).

Первичные конечные точки

• Incidence of cytokine release syndrome (CRS) [Срок оценки: Up to approximately 5 years]

Вторичные конечные точки (8)

• Incidence of serious cytokine release syndrome (CRS) events [Срок оценки: Up to approximately 5 years]
• CRS frequency relative to the start of glofitamab infusions [Срок оценки: Up to approximately 5 years]
• Complete response (CR) rate as determined by independent review facility (IRF) and the investigator [Срок оценки: Up to approximately 5 years]
• Overall response rate (ORR) as determined by IRF and the investigator [Срок оценки: Up to approximately 5 years]
• Duration of response (DOR) [Срок оценки: From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (Up to approximately 5 years)]
• Duration of complete response (DOCR) [Срок оценки: From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (Up to approximately 5 years)]
• Progression-free survival (PFS) as determined by the IRF and the investigator [Срок оценки: From enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first (Up to approximately 5 years)]
• Overall survival (OS) [Срок оценки: From enrollment to date of death from any cause (Up to approximately 5 years)]

Критерии участия

Критерии включения

• Histologically confirmed large B-cell lymphoma (de novo or transformed from FL) with one of the following diagnoses according to World Health Organization, fifth edition: DLBCL Not Otherwise Specified (NOS); High-Grade B-Cell Lymphoma (HGBL), NOS; DLBCL/HGBL with MYC and BCL2 rearrangements
• R/R disease, defined as: relapsed = disease that has recurred following a response that lasted >/= 6 months after completion of the last line of therapy; refractory = disease that did not respond to or that progressed < 6 months after completion of the last line of therapy
• At least one line of prior systemic therapy
• Participants who have failed only one prior line of therapy must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant (ASCT)
• At least one bi-dimensionally measurable (> 1.5 cm) nodal lesion, or one bi-dimensionally measurable (> 1 cm) extranodal lesion, as measured on CT scan
• Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2
• According to the investigator's judgment, participants should be able to receive the step-up dose regimen in an outpatient setting
• Adequate hematologic and renal function

Критерии исключения

• Prior enrollment in Studies GO41943 (NCT04313608), GO41944 (STARGLO; NCT04408638), or Study GO44900 (NCT06624085)
• Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation
• Any history of Waldenstrom's macroglobulinemia
• Primary mediastinal B-cell lymphoma
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
• Contraindication to obinutuzumab, gemcitabine or oxaliplatin, or tocilizumab
• Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
• Prior treatment with gemcitabine or oxaliplatin
• Peripheral neuropathy or paresthesia assessed to be Grade >/= 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 at enrollment
• Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
• Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment
• Primary or secondary CNS lymphoma at the time of recruitment
• Prior CNS involvement that has been definitively treated and confirmed via magnetic resonance imaging (MRI) or cerebrospinal fluid analysis to be in complete remission is permissible
• Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• History of other primary malignancy, with exceptions defined by the protocol
• Significant or extensive cardiovascular disease
• Significant pulmonary disease (including moderate or severe obstructive pulmonary disease)
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment
• Positive for: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); tuberculosis; hepatitis B virus (HBV); hepatitis C virus (HCV); chronic active Epstein-Barr viral infection
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) or progressive multifocal leukoencephalopathy
• Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better (with the exception of alopecia and anorexia)
• Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
• Prior solid organ transplantation or prior allogenic stem cell transplant
• Active autoimmune disease requiring treatment
• Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor agents), within 4 weeks prior to first dose of study treatment
• Ongoing systemic corticosteroid use which, in the opinion of the investigator, puts the participant at increased risk of steroid-related iatrogenic adrenal insufficiency
• Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
• Clinically significant history of cirrhotic liver disease
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participant at high-risk from treatment complications
• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 18 months after the final dose of study treatment

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 33 центра

• Alaska Oncology & Hematology, LLC — Anchorage
• Community Cancer Institute (CCI) — Clovis
• Providence Medical Foundation — Fullerton
• Los Angeles Cancer Network — Glendale
• Valkyrie Clinical Trials — Los Angeles
• Valkyrie Clinical Trials — Panorama City
• Zuckerberg San Francisco General Hospital — San Francisco
• The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Cente — Torrance
• … и ещё 25 центров

Франция · 5 центров

• CHU de Grenoble — La Tronche
• Chu de Montpellier-St Eloi — Montpellier
• CHU de Bordeaux — Pessac
• CHU DE RENNES - CHU Pontchaillou — Rennes
• Chu De Tours — Tours

Италия · 5 центров

• Istituto Nazionale Tumori Irccs Fondazione g. Pascale — Naples
• IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori" — Meldola
• A.O. Spedali Civili Di Brescia-P.O. Spedali Civili — Brescia
• Irccs Istituto Europeo Di Oncologia (IEO) — Milan
• Istituto Clinico Humanitas — Rozzano

Германия · 4 центра

• CAMPUS BENJAMIN FRANKLIN CharitéCentrum 14 Med.Klinik f.Hämatologie u.Onkologie — Berlin
• Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) — Berlin
• Universitätsklinikum Köln — Cologne
• Otto von Guericke Uni Magdeburg Uniklinik — Magdeburg

South Korea · 3 центра

• Seoul National University Bundang Hospital — Seongnam-si
• Seoul National University Hospital — Seoul
• Asan Medical Center — Seoul

Канада · 2 центра

• Arthur J.E. Child Comprehensive Cancer Center — Calgary
• CancerCare Manitoba (CCMB) — Winnipeg

Австралия · 1 центр

• Epworth Hospital — East Melbourne

Идентификаторы

NCT: NCT06806033 · GO45434

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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