A Phase III Study Evaluating Glofitamab in Combination With Gemcitabine + Oxaliplatin vs Rituximab in Combination With Gemcitabine + Oxaliplatin in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04408638

Collaborator

(none)

270

Enrollment

Locations

Arms

49.7

Anticipated Duration (Months)

3.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of glofitamab in combination with gemcitabine plus oxaliplatin (Glofit-GemOx) compared with rituximab in combination with gemcitabine plus oxaliplatin (R-GemOx) in patients with R/R DLBCL.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-cell Lymphoma	Drug: Obinutuzumab Drug: Glofitamab Drug: Rituxumab Drug: Tocilizumab Drug: Gemcitabine Drug: Oxaliplatin	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

270 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Glofitamab in Combination With Gemcitabine Plus Oxaliplatin Versus Rituximab in Combination With Gemcitabine and Oxaliplatin in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Actual Study Start Date :

Feb 23, 2021

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Apr 15, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glofit-GemOx Participants will receive up to 8 cycles of glofitamab (Glofit) in combination with gemcitabine and oxaliplatin (GemOx), followed by up to 4 cycles of glofitamab monotherapy. A single dose of obinutuzumab will be administered 7 days prior to the first dose of glofitamab. Treatment is administered in 21-day cycles.	Drug: Obinutuzumab Participants will receive a single dose of intravenous (IV) obinutuzumab pre-treatment 7 days prior to the first dose of glofitamab. Drug: Glofitamab Participants will receive IV glofitamab for up to 12 cycles. Drug: Tocilizumab Participants will receive IV tocilizumab as needed for treatment of cytokine-release syndrome (CRS). Drug: Gemcitabine Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles. Drug: Oxaliplatin Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.
Experimental: R-GemOx Participants will receive rituxumab (R) in combination with gemcitabine and oxaliplatin (GemOx) for up to 8 cycles. Treatment is administered in 21-day cycles.	Drug: Rituxumab Participants will receive IV rituxumab on Day 1 of each cycle for up to 8 cycles. Drug: Gemcitabine Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles. Drug: Oxaliplatin Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

Arm

Intervention/Treatment

Experimental: Glofit-GemOx

Participants will receive up to 8 cycles of glofitamab (Glofit) in combination with gemcitabine and oxaliplatin (GemOx), followed by up to 4 cycles of glofitamab monotherapy. A single dose of obinutuzumab will be administered 7 days prior to the first dose of glofitamab. Treatment is administered in 21-day cycles.

Drug: Obinutuzumab

Participants will receive a single dose of intravenous (IV) obinutuzumab pre-treatment 7 days prior to the first dose of glofitamab.

Drug: Glofitamab

Participants will receive IV glofitamab for up to 12 cycles.

Drug: Tocilizumab

Participants will receive IV tocilizumab as needed for treatment of cytokine-release syndrome (CRS).

Drug: Gemcitabine

Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.

Drug: Oxaliplatin

Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

Experimental: R-GemOx

Participants will receive rituxumab (R) in combination with gemcitabine and oxaliplatin (GemOx) for up to 8 cycles. Treatment is administered in 21-day cycles.

Drug: Rituxumab

Participants will receive IV rituxumab on Day 1 of each cycle for up to 8 cycles.

Drug: Gemcitabine

Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.

Drug: Oxaliplatin

Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

Outcome Measures

Primary Outcome Measures

Overall survival (OS), defined as the time from randomization to date of death from any cause [Up to 3.5 years]

Secondary Outcome Measures

Progression-free survival (PFS), defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the Independent Review Committee (IRC) [Up to 3.5 years]
PFS, defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the investigator [Up to 3.5 years]
Complete response (CR) rate, defined as the proportion of patients whose best overall response is a CR on positron emission tomography/computed tomography (PET/CT) during the study, as determined by the IRC [Up to 3.5 years]
CR rate, defined as the proportion of patients whose best overall response is a CR on positron emission tomography/computed tomography (PET/CT) during the study, as determined by the investigator [Up to 3.5 years]
Objective response rate (ORR), defined as the proportion of patients whose best overall response is a partial response (PR) or a CR during the study, as determined by the IRC [Up to 3.5 years]
ORR, defined as the proportion of patients whose best overall response is a partial response (PR) or a CR during the study, as determined by the investigator [Up to 3.5 years]
Duration of objective response (DOR), defined as the time from the first occurrence of a documented objective response (CR or PR) to disease progression, or death from any cause, whichever occurs first [Up to 3.5 years]
Duration of CR, defined as the time from the first occurrence of a documented CR to disease progression, or death from any cause, whichever occurs first [Up to 3.5 years]
Time to deterioration in physical functioning and fatigue, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) [Up to 3.5 years]
Time to deterioration in lymphoma symptoms, as measured by the Functional Assessment of Cancer Therapy-Lymphoma subscale (FACT-Lym LymS) [Up to 3.5 years]
Percentage of Participants with Adverse Events [Up to 3.5 years]
Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity, and study treatment discontinuation because of adverse events [Up to 3.5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Histologically confirmed diffuse large B-cell lymphoma (DLBCL), not otherwise specified
Relapsed/refractory (R/R) disease, defined as follows: Relapsed = disease that has recurred ≥6 months after completion of the last line of therapy; Refractory = disease that either progressed during the last line of therapy or progressed within 6 months (<6 months) of the last line of prior therapy
At least one (≥1) 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, as defined by the study protocol
Confirmed availability of tumor tissue, unless unobtainable per investigator assessment. Freshly collected biopsy is preferred. Archival tissue is acceptable
At least one bi-dimensionally measurable (≥1.5 cm) nodal lesion, or one bi-dimensionally measurable (≥1 cm) extranodal lesion, as measured on computed tomography (CT) scan
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
Adequate hematologic function (unless attributable to the underlying disease, as established by extensive bone marrow involvement or associated with hypersplenism secondary to the involvement of the spleen by DLBCL per the investigator), as defined by the study protocol
Adequate renal function, defined as an estimated creatinine clearance ≥30 mL/min

Exclusion Criteria

Patient has failed only one prior line of therapy and is a candidate for stem cell transplantation
History of transformation of indolent disease to DLBCL
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma not otherwise specified, as defined by 2016 WHO guidelines
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, rituximab, gemcitabine or oxaliplatin, or tocilizumab
Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
Peripheral neuropathy assessed to be Grade >1 according to 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 central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma
Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative 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
Suspected or latent tuberculosis
Positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
Known or suspected chronic active Epstein-Barr viral infection
Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
Known history of progressive multifocal leukoencephalopathy
Adverse events from prior anti-cancer therapy 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
Prior allogeneic stem cell transplant
Active autoimmune disease requiring treatment
Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 4 weeks prior to first dose of study treatment
Corticosteroid therapy within 2 weeks prior to first dose of study treatment (exceptions defined by study protocol)
Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
Clinically significant history of cirrhotic liver disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-3300
2	Banner Health MD Anderson AZ	Gilbert	Arizona	United States	85234
3	Community Cancer Institute (CCI)	Fresno	California	United States	93720
4	Baptist Medical Center - Jacksonville	Jacksonville	Florida	United States	32207-8202
5	Baptist - MD Anderson Cancer Center	Jacksonville	Florida	United States	32207
6	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
7	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
8	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21287
9	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
10	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
11	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
12	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
13	Duke University Medical Center	Durham	North Carolina	United States	27705
14	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
15	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
16	Prince of Wales Hospital; Haematology	Randwick	New South Wales	Australia	2031
17	Monash Health Monash Medical Centre	Clayton	Victoria	Australia	3168
18	St Vincent's Hospital Melbourne	Fitzroy	Victoria	Australia	3065
19	Peter Maccallum Cancer Centre	Melbourne	Victoria	Australia	3000
20	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
21	UZ Gent	Gent		Belgium	9000
22	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
23	CHU Sart-Tilman	Liège		Belgium	4000
24	Beijing Cancer Hospital	Beijing		China	100142
25	Peking University Third Hospital	Beijing		China	100191
26	West China Hospital, Sichuan University	Chengdu		China	610041
27	Sun Yet-sen University Cancer Center	Guangzhou		China	510060
28	Harbin Medical University Cancer Hospital	Harbin		China	150081
29	Jiangsu Province Hospital	Nanjing		China	210036
30	Fudan University Shanghai Cancer Center	Shanghai City		China	200120
31	Tianjin Cancer Hospital	Tianjin		China	300060
32	Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology	Wuhan City		China	430022
33	Zhejiang Cancer Hospital	Zhejiang		China	310022
34	Henan Cancer Hospital	Zhengzhou		China	450008
35	Aarhus Universitetshospital Skejby; Blodsygdomme	Aarhus N		Denmark	8200
36	Rigshospitalet; Hæmatologisk Klinik	København Ø		Denmark	2100
37	Institut Bergonie; Hematologie Oncologie	Bordeaux		France	33076
38	Hopital Henri Mondor; 51 Av Mal Lattre De Tassigny	Creteil		France	94010
39	Hopital Claude Huriez; Hematologie	Lille		France	59037
40	CHU DE MONTPELLIER-ST ELOI; Département d'Hématologie Clinique	Montpellier		France	34295
41	Centre Hospitalier Lyon Sud	Pierre Benite		France	69495
42	CHU Pontchaillou; Service Hématologie	Rennes		France	35003
43	Städtisches Klinikum Dessau	Dessau-Roßlau		Germany	06847
44	Universitatsklinikum Frankfurt	Frankfurt		Germany	60590
45	Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Medizinische Klinik I	Giessen		Germany	35392
46	Universitaetsklinikum Heidelberg	Heidelberg		Germany	69120
47	Universitaetsklinikum Regensburg	Regensburg		Germany	93053
48	Katharinenhospital Stuttgart; Klinik für Hämatologie, Onkologie und Palliativmedizin	Stuttgart		Germany	70174
49	Pusan National University Hospital	Busan		Korea, Republic of	49241
50	National Cancer Center	Goyang-si		Korea, Republic of	10408
51	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13605
52	Seoul National University Hospital	Seoul		Korea, Republic of	03080
53	Asan Medical Center	Seoul		Korea, Republic of	05505
54	Samsung Medical Center	Seoul		Korea, Republic of	06351
55	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland
56	Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli	Lublin		Poland	20-090
57	Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn		Poland	10-228
58	Szpital Wojewodzki w Opolu, Oddzial Hematologii i Onkologii Hematologicznej	Opole		Poland	45-061
59	Szpital Kliniczny im. Heliodora Święcickiego; Oddzial Hematologii i Transplantacji Szpiku	Poznań		Poland	60-569
60	Instytut Hematologii i Transfuzjologii; Klinika Hematologii	Warszawa		Poland	02-776
61	Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku	Wrocław		Poland	50-367
62	PanOncology Trials; Hospital Oncológico, Puerto Rico Medical Center	San Juan		Puerto Rico	00935
63	Hospital Universitario Marques de Valdecilla; Servicio de Hematologia	Santander	Cantabria	Spain	39008
64	Hospital Universitari Vall d'Hebron; Servicio de Hematologia	Barcelona		Spain	08035
65	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona		Spain	08036
66	Hospital Universitario la Paz; Servicio de Hematologia	Madrid		Spain	28046
67	Hospital Universitario Virgen del Rocio; Servicio de Hematologia	Sevilla		Spain	41013
68	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia		Spain	46010
69	Inselspital Bern, Insel-Gruppe AG	Bern		Switzerland	3010
70	Universitätsspital Zürich	Zürich		Switzerland	8091
71	Chang Gung Medical Foundation - Kaohsiung; Oncology; Division of Hematology-Oncology	Kaoisung		Taiwan	833
72	Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology	Taoyuan		Taiwan	333
73	Taichung Veterans General Hospital	Xitun Dist.		Taiwan	40705
74	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
75	St James's Institute of Oncology; Dept of Haematology	Leeds		United Kingdom	LS9 7TF
76	UCLH - Clinical Trials Pharmacy B&D Centre	London		United Kingdom	N7 9NH
77	Christie Hospital; Department of Haematology and Transplant	Manchester		United Kingdom	M20 4BX
78	Nottingham City Hospital; Dept of Haematology	Nottingham		United Kingdom	NG5 1PB
79	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD