Feasibility Trial of Glofitamab in a Response Adapted Approach Incorporating Interim FDG PET and ctDNA to Optimize Primary Therapy of DLBCL (GRAIL)

NCT06050694 | Recruiting Phase 2 DMC

• 1 other identifier: OZM-121
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase ll study of participants with untreated diffuse large B Cell lymphoma (DLBCL).

Conditions

Diffuse Large B Cell Lymphoma (DLBCL)

Outcome Measures

Primary Outcomes (1)

• To demonstrate the feasibility of a ctDNA and FDG-PET interim response adapted approach (iRAAp) for the primary therapy of DLBCL

  Determine the proportion of patients that can have results available to risk adapt cycle treatment starting at cycle 3 based on interim testing (ctDNA collected immediately prior to cycle 2 of Pola-R-CHP, PET scan following cycle 2 of Pola-R-CHP ie. PET2). Treat the ctDNA low-risk patients (favourable ctDNA and PET2) with abbreviated chemotherapy (total 4 cycles of Pola-R-CHP with 2 courses of rituximab as a monotherapy). Treat the ctDNA high-risk patients (unfavourable ctDNA and/or PET2) with a novel treatment approach (complete 3 cycles of Pola-R-CHP and then start novel approach).

  At the end of cycle 1 (ctDNA) and cycle 2 (PET)(each cycle is 21 days)

Secondary Outcomes (5)

• Event-free survival (EFS)

  baseline to month 24

• Incidence of treatment emergent adverse events

  baseline to cycle 6 (each cycle is 21 days)

• Progression free survival (PFS) at 12 months and 24 months

  baseline to 24 months

• To evaluate changes in health-related quality of life (HRQOL)

  baseline through year 2

• Overall survival (OS) at 12 months and 24 months

  baseline to 24 months

Study Arms (2)

Pola-R-CHP

NO INTERVENTION

Protocol induction: Cycle 1-2 Low-risk group: Cycle 3-4 polatuzumab vedotin 1.8 mg/kg, cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 on day 1, prednisone 100 mg daily days 1-5, and rituximab 375 mg/m2 within 72 hours of polatuzumab vedotin Cycle 5-6 rituximab 375 mg/m2 on day 1 of cycle 5 and cycle 6

Pola-R-CHP and glofitamab

EXPERIMENTAL

High-risk group: Cycle 3-6 polatuzumab vedotin 1.8 mg/kg, cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 on day 1, prednisone 100 mg daily days 1-5, rituximab 375 mg/m2 within 72 hours of polatuzumab vedotin and Glofitamab 2.5 mg Cycle 3 Day 8 and 10 mg on Day 15 Cycles 3-6

Drug: glofitamab

Interventions

glofitamab DRUG

Glofitamab 2.5 mg Cycle 3 Day 8 and 10 mg on Day 15 Cycles 3-6

Pola-R-CHP and glofitamab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women ≥ 18 years of age deemed eligible for treatment with full-dose Pola- R-CHP and possible treatment with glofitamab by the qualified investigator.
• Histologic diagnosis of DLBCL and variants according to the WHO 201613 or WHO 202254 classification including DLBCL non-organ-specific (NOS), Germinal centre B-cell type, activated B-cell type, T-cell/histiocyte-rich large B-cell lymphoma, Epstein-Barr Virus (EBV) + DLBCL, Primary mediastinal/thymic large B-cell lymphoma, High grade B-cell lymphoma with myelocytomatosis oncogene (MYC) and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements, High grade B cell lymphoma NOS including lymphomas transformed from previously untreated indolent lymphomas.
• Previously untreated DLBCL with the following exceptions: (a) prior radiotherapy for palliation (not localized), (b) up to 7 days of corticosteroids (prednisone 100mg/day equivalent).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Presence of at least one radiologically measurable nodal or extranodal mass. A measurable nodal mass must have a longest diameter ≥1.5 cm. A measurable extranodal mass should have a longest diameter ≥1.0 cm.16
• Left ventricular ejection fraction (LVEF) ≥ 50%, as determined on cardiac multiple- gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
• Women of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and up to 18 months after the last dose of or protocol therapy. Men who are sexually active must use highly effective methods of contraception during treatment and up to 6 months after the last dose of protocol therapy. Men require an agreement to remain abstinent (ie, refrain from heterosexual intercourse) or use a condom, and an agreement to refrain from donating sperm. Periodic abstinence and withdrawal are not acceptable methods of contraception. Fertility preservation options should be discussed. Examples of highly effective contraceptive methods include an agreement to remain abstinent (ie, refrain from heterosexual intercourse), bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• Willing and able to participate in all required evaluations and procedures in this study.
• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained by the patient or legally acceptable representative before any study-specific procedures are performed.

You may not qualify if:

• Current/past history of central nervous system (CNS) lymphoma.
• Prior exposure to any anthracycline, rituximab or cluster of differentiation 3 (CD3) targeted bispecific antibody.
• Prior malignancy (or any other malignancy requiring active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to \< 5 years. Subjects receiving adjuvant hormonal therapy for early breast or prostate cancer are eligible.
• Significant or extensive cardiovascular disease such as New York Heart Association Class III or IV cardiac disease or Objective Assessment Class C or D, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study.
• 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 (bronchospasm, obstructive pulmonary disease), and known autoimmune diseases.
• Patients with a known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• History of illicit drug or alcohol abuse within 12 months prior to screening, in the Investigator's judgment.
• Known active infection, or reactivation of a latent infection, whether bacterial, viral (including, but not limited to, EBV, cytomegalovirus (CMV), hepatitis B, hepatitis C, and human immunodeficiency virus (HIV), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 4 weeks of dosing. Individuals with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy, have a cluster of differentiation 4 (CD4) count ≥ 200/μL, and have an undetectable viral load. HIV positive patients should be monitored per local/institutional standards while receiving study treatment.
• Known history of drug-specific hypersensitivity or anaphylaxis to study drugs (glofitamab and individual components of Pola-R-CHP), including grade III or greater allergic reactions to any monoclonal antibody.
• Known Type I hypersensitivity or anaphylactic reactions to murine proteins, Chinese Hamster Ovary (CHO) cell proteins, or to any component of Rituximab
• Current history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Patients with a history of stroke who have not experienced a stroke or transient ischemic attack within the past 2 years and have no residual neurological deficient, as judged by the investigator, are allowed.
• Active autoimmune disease which is not well controlled by therapy:
• Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible. Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Participants with active autoimmune disease with dermatologic manifestations are eligible for the study.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (3)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

NOT YET RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

glofitamab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• John Kuruvilla, FRCPC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Kuruvilla, FRCPC

CONTACT

4169462821; LymphomaClinicalTrials@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2023
• First Posted: September 22, 2023
• Study Start: January 24, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)