Non Hodgkin Lymphoma Clinical Trial

A Dose Escalation Study of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-Treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin’s Lymphoma

Summary

This is a Phase I/II, multicenter, open-label, dose-escalation study designed to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of a novel T-Cell bispecific (TCB), glofitamab, administered by intravenous (IV) infusion as a single agent and in combination with obinutuzumab, following pre-treatment with a one-time, fixed dose of obinutuzumab. This entry-to-human study is divided in 3 parts: dose escalation (Parts I and II) and dose expansion (Part III). Single-participant dose-escalation cohorts will be used in Part I, followed by conversion to multiple participant dose-escalation cohorts (Part II), in order to define a tentative maximum tolerated dose (MTD) or optimal biological dose (OBD). The expansion cohorts (Part III) will be initiated when the tentative MTD/OBD is defined, to further evaluate the safety, PK and therapeutic activity of glofitamab.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Depending upon study part, a history or status of: 1) a histologically-confirmed hematological malignancy that is expected to express cluster of differentiation (CD)20; 2) relapse after or failure to respond to at least one prior treatment regimen; and 3) no available treatment options that are expected to prolong survival (e.g., standard chemotherapy or autologous stem cell transplant [ASCT])
Measurable disease, defined as at lease one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally measureable extranodal lesion, defined as > 1.0 cm in its longest dimension
Able to provide a fresh biopsy from a safely accessible site, per investigator determination, providing the patient has more than one measurable target lesion
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Life expectancy of >/=12 weeks
AEs from prior anti-cancer therapy must have resolved to Grade less than or equal to ( Adequate liver, hematological and renal function
Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic Hepatitis B virus (HBV) infection
Negative test results for Hepatitis C virus (HCV) and human immunodeficiency virus (HIV)
Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential. Women who are not of childbearing potential who are considered to be post-menopausal (at least 12 months of non-therapy amenorrhea) or surgically sterile (absence of ovaries and/or uterus) are not required to have a pregnancy test

Exclusion Criteria:

Inability to comply with protocol mandated hospitalizations and restrictions
Participants with chronic lymphocytic leukemia (CLL), Burkitt lymphoma and lymphoplasmacytic lymphoma
Participants with a known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
Participants with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to obinutuzumab infusion or by clinical judgment in the absence of a positive blood culture
Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing
Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 [anti-CTLA4], anti-programmed death 1 [anti-PD1] and anti-programmed death ligand 1 [anti-PDL1]) within 4 weeks or five half-lives of the drug, whichever is shorter, before obinutuzumab infusion on Cycle 1 Day -7
History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents
Documented refractoriness to an obinutuzumab-containing regimen
Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent, including chimeric antigen receptor therapy (CAR-T) within 4 weeks prior to obinutuzumab infusion
Prior solid organ transplantation
Prior allogeneic SCT
Autologous SCT within 100 days prior to obinutuzumab infusion
Participant with history of confirmed progressive multifocal leukoencephalopathy (PML)
Current or past history of central nervous system (CNS) lymphoma
Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Participants with a past history of stroke that have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits are allowed.
Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders and known autoimmune diseases
Participants with another invasive malignancy in the last 2 years (with the exception of basal cell carcinoma and tumors deemed by the Investigator to be of low likelihood for recurrence)
Significant or extensive history of cardiovascular disease such as New York Heart Association Class III or IV or Objective Class C or D cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina
Administration of a live, attenuated vaccine within 4 weeks before obinutuzumab infusion or anticipation that such a live attenuated vaccine will be required during the study
Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within two weeks prior to obinutuzumab infusion. Treatment with corticosteroid 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
History of autoimmune disease, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus, erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Participants with a remote history of, or well controlled autoimmune disease, may be eligible to enroll after consultation with the Medical Monitor
In Part III DLBCL dexamethasone cohort, patients with a history of hypersensitivity to dexamethasone or systemic corticosteroids will be excluded

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

860

Study ID:

NCT03075696

Recruitment Status:

Recruiting

Sponsor:

Hoffmann-La Roche

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There are 41 Locations for this study

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Cedars Sinai Medical Center
Los Angeles California, 90048, United States
Ingalls Memorial Hospital
Harvey Illinois, 60426, United States
University of Kansas Medical Centre
Kansas City Kansas, 66160, United States
University of Michigan
Ann Arbor Michigan, 48109, United States
Washington University; Wash Uni. Sch. Of Med
Saint Louis Missouri, 63110, United States
Mount Sinai Medical Center
New York New York, 10029, United States
MSKCC
New York New York, 10065, United States
Allegheny Health Network (Pittsburg PA)
Pittsburgh Pennsylvania, 15212, United States
Hunstman Cancer Institute
Salt Lake City Utah, 84112, United States
Virginia Commonwealth University Medical Center
Richmond Virginia, 23230, United States
Swedish Cancer Inst.
Seattle Washington, 98104, United States
Prince of Wales Hospital; Haematology
Randwick New South Wales, 2031, Australia
Peter Maccallum Cancer Centre
Melbourne Victoria, 3000, Australia
Cliniques Universitaires St-Luc
Bruxelles , 1200, Belgium
UZ Gent
Gent , 9000, Belgium
Princess Margaret Cancer Center
Toronto Ontario, M5G 1, Canada
Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK
Praha 2 , 128 0, Czechia
Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT
København Ø , 2100, Denmark
Helsinki University Central Hospital; Dept of Oncology
Helsinki , 00250, Finland
Hopital Henri Mondor; Hematologie Clinique
Creteil , 94010, France
Hopital Claude Huriez; Hematologie
Lille , 59037, France
CHU Saint Eloi; Service d'Hématologie Clinique
Montpellier , 34295, France
Ch Lyon Sud; Hemato Secteur Jules Courmont
Pierre Benite , 69495, France
CHU DE RENNES - CHU Pontchaillou; Service d'Hématologie Clinique Adulte
Rennes , 35033, France
AUSL della Romagna; Dipartimento Oncoematologico - U.O.C. Oncologia
Ravenna Emilia-Romagna, 48121, Italy
Fond. IRCCS Istituto Nazionale Tumori; S. C. Ematologia
Milano Lombardia, 20133, Italy
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
Rozzano Lombardia, 20089, Italy
A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia
Torino Piemonte, 10126, Italy
Auckland Cancer Trial Centre; Ward 64, Auckland City Hospital,
Auckland , 1023, New Zealand
Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz
Gdańsk , 80-21, Poland
Szpital Kliniczny im. Heliodora Święcickiego; Oddzial Hematologii i Transplantacji Szpiku
Poznań , 60-56, Poland
Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz
Warszawa , 02-78, Poland
Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
Wrocław , 50-36, Poland
Hospital Universitari Germans Trias i Pujol; Servicio de Hematologia
Badalona Barcelona, 08915, Spain
Hospital Duran i Reynals L'Hospitalet; Hematology Department
L'Hospitalet de Llobregat Barcelona, 08908, Spain
Hospital Universitario Marques de Valdecilla; Servicio de Hematologia
Santander Cantabria, 39008, Spain
Hospital del Mar; Servicio de Hematologia
Barcelona , 08003, Spain
Hospital Universitari Vall d'Hebron; Servicio de Hematologia
Barcelona , 08035, Spain
Hospital Univ. 12 de Octubre; Servicio de Hematologia
Madrid , 28041, Spain
China Medical University Hospital; Oncology and Hematology
Taichung , 404, Taiwan
National Taiwan Universtiy Hospital; Division of Hematology
Taipei , 100, Taiwan

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

860

Study ID:

NCT03075696

Recruitment Status:

Recruiting

Sponsor:


Hoffmann-La Roche

How clear is this clinincal trial information?

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