Clinical trial NCT04980222: A Study to Evaluate the Safety and Efficacy of Glofitamab in Combination With Rituximab (R) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Circulating Tumor (ct)DNA High-Risk Patients With Untreated Diffuse Large B-Cell Lymphoma
Official title: A Phase II Study Evaluating the Safety and Efficacy of Glofitamab in Combination With Rituximab (R) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Circulating Tumor (ct)DNA High-Risk Patients With Untreated Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-07-28
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This Phase II, open-label, multicenter study will evaluate the safety, efficacy, and pharmacokinetics of glofitamab in combination with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in individuals with circulating tumor DNA (ctDNA) high-risk diffuse large B-cell lymphoma (DLBCL), as the first line of treatment.


Eligibility criteria: Inclusion Criteria:

* Previously untreated patients with CD20-positive DLBCL, including one of the following diagnoses made according to the 2016 World Health Organization (WHO) classification of lymphoid neoplasms

  * DLBCL, not otherwise specified, including GCB and ABC/non-GCB types as well as double-expressor lymphoma (coexpression of MYC and BCL2)
  * High-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 translocations
  * Patients with de novo transformed follicular lymphoma (patients with discordant bone marrow involvement, i.e., evidence of low-grade histology in bone marrow) may be considered after discussion with the Medical Monitor
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
* International Prognostic Index (IPI): 2-5
* Life expectancy of at least 6 months
* Adequate biomarker blood samples prior to initiation of R-CHOP on Day 1 of Cycle 1 and on Day 1 of Cycle 2 submitted for screening for determination of ctDNA status
* At least one bi-dimensionally fluorodeoxyglucose (FDG)-avid measurable lymphoma lesion on positron emission tomography/computed tomography (PET/CT) scan
* Left ventricular ejection fraction (LVEF) \>=50%, as determined on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
* Adequate hematopoietic function
* Contraception use

Additional Inclusion Criterion for ctDNA High-Risk Participants:

* Plasma sample evaluated to be ctDNA high risk

Exclusion Criteria:

* Current diagnosis of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma (gray-zone lymphoma), primary mediastinal (thymic) large B-cell lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, Burkitt lymphoma, central nervous system (CNS) lymphoma (primary or secondary involvement), primary effusion DLBCL, and primary cutaneous DLBCL
* Contraindication to any of the individual components of R-CHOP, including prior receipt of anthracyclines, history of severe allergic or anaphylactic reactions to murine monoclonal antibodies, or known sensitivity or allergy to murine products
* Prior treatment for indolent lymphoma
* Prior solid organ or allogeneic stem cell transplant
* Prior therapy for DLBCL and high-grade B-cell lymphoma (HGBCL) with the exception of palliative, short-term treatment with corticosteroids
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the final dose of R-CHOP, 3 months after the final dose of tocilizumab (if applicable), or 2 months after the final dose of glofitamab

Primary outcomes:
measure: End of Treatment Complete Response (EOT CR) Rate
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Overall Response Rate (ORR) at the EOT
timeFrame: Up to approximately 24 months
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 24 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 24 months
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to 90 days after the final dose of study treatment
measure: Serum Concentration of Glofitamab
timeFrame: At pre-defined intervals up to approximately 10 months
measure: Maximum Concentration (Cmax) of Glofitamab
timeFrame: At pre-defined intervals up to approximately 10 months
measure: Total Exposure (AUC) of Glofitamab
timeFrame: At pre-defined intervals up to approximately 10 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute Inpatient Investigational Pharmacy
state: California
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Saint Louis
country: United States
facility: Washington University; Wash Uni. Sch. Of Med
state: Missouri
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering - Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan-Kettering; Cancer Center
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center at Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Cancer Center at Nassau
state: New York
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital Skejby
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
city: Wroc?aw
country: Poland
facility: Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Univ. 12 de Octubre; Servicio de Hematologia
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: