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JOURNAL ONKOLOGIE – STUDIE

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

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NCT-Nummer:
NCT04408638

Studienbeginn:
Januar 2021

Letztes Update:
11.01.2021

Wirkstoff:
Obinutuzumab, Glofitamab, Rituxumab, Tocilizumab, Gemcitabine, Oxaliplatin

Indikation (Clinical Trials):
Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Hoffmann-La Roche

Collaborator:
-

Studienleiter

Clinical Trials
Study Director
Hoffmann-La Roche

Kontakt

Reference Study ID Number: GO41944 www.roche.com/about_roche/roche_worldwide.htm
Kontakt:
Phone: 888-662-6728
E-Mail: global-roche-genentech-trials@gene.com» Kontaktdaten anzeigen

Studienlocations (3 von 74)

Städtisches Klinikum Dessau
06847 Dessau-Roßlau
(Sachsen-Anhalt)
Germany» Google-Maps
Universitatsklinikum Frankfurt
60590 Frankfurt
(Hessen)
Germany» Google-Maps
Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Medizinische Klinik I
35392 Giessen
(Hessen)
Germany» Google-Maps
Universitätsklinikum Heidelberg
69120 Heidelberg
(Baden-Württemberg)
Germany» Google-Maps
Universitaetsklinikum Regensburg
93053 Regensburg
(Bayern)
Germany» Google-Maps
Katharinenhospital Stuttgart; Klinik für Hämatologie, Onkologie und Palliativmedizin
70174 Stuttgart
(Baden-Württemberg)
Germany» Google-Maps
University of Alabama at Birmingham
35294-3300 Birmingham
United States» Google-Maps
University of Maryland Medical Center
21201 Baltimore
United States» Google-Maps
University of Mississippi Medical Center
39216 Jackson
United States» Google-Maps
Rutgers Cancer Institute of New Jersey
08901 New Brunswick
United States» Google-Maps
Icahn School of Medicine at Mount Sinai
10029 New York
United States» Google-Maps
Providence Portland Medical Center
97213 Portland
United States» Google-Maps
Thomas Jefferson Uni Hospital
19107 Philadelphia
United States» Google-Maps
University of Pittsburgh - Hillman Cancer Center
15232-1301 Pittsburgh
United States» Google-Maps
Providence Regional Cancer Partnership
98201 Everett
United States» Google-Maps
Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
430022 Wuhan City
China» Google-Maps
Arhus Universitetshospital Skejby; Blodsygdomme
8200 Aarhus N
Denmark» Google-Maps
Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT
2100 København Ø
Denmark» Google-Maps
Pusan National University Hospital
49241 Busan
Korea, Republic of» Google-Maps
Seoul National University Bundang Hospital
13605 Seongnam-si
Korea, Republic of» Google-Maps
Seoul National University Hospital
03080 Seoul
Korea, Republic of» Google-Maps
Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli
20-090 Lublin
Poland» Google-Maps
Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
10-228 Olsztyn
Poland» Google-Maps
Szpital Wojewodzki w Opolu, Oddzial Hematologii i Onkologii Hematologicznej
45-061 Opole
Poland» Google-Maps
Szpital Kliniczny; Oddzial Hematologii i Transplantacji Szpiku
60-569 Poznań
Poland» Google-Maps
Instytut Hematologii i Transfuzjologii; Klinika Hematologii
02-776 Warszawa
Poland» Google-Maps
Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
50-367 Wrocław
Poland» Google-Maps
PanOncology Trials; Hospital Oncológico, Puerto Rico Medical Center
00935 San Juan
Puerto Rico» Google-Maps
Hospital Universitario Marques de Valdecilla; Servicio de Hematologia
39008 Santander
Spain» Google-Maps
Hospital Universitari Vall d'Hebron; Servicio de Hematologia
08035 Barcelona
Spain» Google-Maps
Hospital Clínic i Provincial; Servicio de Hematología y Oncología
08036 Barcelona
Spain» Google-Maps
Hospital Universitario la Paz; Servicio de Hematologia
28046 Madrid
Spain» Google-Maps
Hospital Universitario Virgen del Rocio; Servicio de Hematologia
41013 Sevilla
Spain» Google-Maps
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
46010 Valencia
Spain» Google-Maps
Beatson West of Scotland Cancer Centre
G12 0YN Glasgow
United Kingdom» Google-Maps
St James's Institute of Oncology; Dept of Haematology
LS9 7TF Leeds
United Kingdom» Google-Maps
UCLH - Clinical Trials Pharmacy B&D Centre
N7 9NH London
United Kingdom» Google-Maps
Christie Hospital; Department of Haematology and Transplant
M20 4BX Manchester
United Kingdom» Google-Maps
Newcastle University; Northern Institute For Cancer Research Paul O'gorman Building
NE1 4LP Newcastle
United Kingdom» Google-Maps
Nottingham City Hospital; Dept of Haematology
NG5 1PB Nottingham
United Kingdom» Google-Maps
Southampton General Hospital
SO16 6YD Southampton
United Kingdom» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Overall survival (OS), defined as the time from randomization to date of death from any cause (Time Frame - Up to 3.5 years)



Secondary outcome:

1. 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) (Time Frame - Up to 3.5 years)

2. 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 (Time Frame - Up to 3.5 years)

3. 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 (Time Frame - Up to 3.5 years)

4. 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 (Time Frame - Up to 3.5 years)

5. 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 (Time Frame - Up to 3.5 years)

6. 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 (Time Frame - Up to 3.5 years)

7. 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 (Time Frame - Up to 3.5 years)

8. 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 (Time Frame - Up to 3.5 years)

9. 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) (Time Frame - Up to 3.5 years)

10. Time to deterioration in lymphoma symptoms, as measured by the Functional Assessment of Cancer Therapy-Lymphoma subscale (FACT-Lym LymS) (Time Frame - Up to 3.5 years)

11. Percentage of Participants with Adverse Events (Time Frame - Up to 3.5 years)

12. Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity, and study treatment discontinuation because of adverse events (Time Frame - Up to 3.5 years)

Studien-Arme

  • 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.
  • 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.

Geprüfte Regime

  • Obinutuzumab:
    Participants will receive a single dose of intravenous (IV) obinutuzumab pre-treatment 7 days prior to the first dose of glofitamab.
  • Glofitamab:
    Participants will receive IV glofitamab for up to 12 cycles.
  • Rituxumab:
    Participants will receive IV rituxumab on Day 1 of each cycle for up to 8 cycles.
  • Tocilizumab:
    Participants will receive IV tocilizumab as needed for treatment of cytokine-release syndrome (CRS).
  • Gemcitabine:
    Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.
  • Oxaliplatin:
    Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

Quelle: ClinicalTrials.gov


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