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Diffuse Large B Cell Lymphoma (DLBCL)Phase 2GRAILNCT06050694

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

A Phase 2 study testing glofitamab in people with Diffuse Large B Cell Lymphoma (DLBCL), run by University Health Network, Toronto at 3 sites in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B Cell Lymphoma (DLBCL)
What is being tested?
glofitamab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
3 sitesCanada
Study dates
24 Jan 2025to Nov 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • 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)
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  • 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.
  • Participants with a history of autoimmune hepatitis, systemic lupus erythematosus, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, multiple sclerosis, or glomerulonephritis will be excluded.
  • Participants with a history of immune thrombocytopenic purpura, autoimmune hemolytic anemia, Guillain-Barré syndrome, myasthenia gravis, myositis, rheumatoid arthritis, vasculitis, or other autoimmune disease will be excluded unless they have not required systemic therapy in the last 12 months
  • Major surgical procedure within 4 weeks of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
  • Administration of a live, attenuated vaccine within 4 weeks before study treatment infusion on Cycle 1/Day 1 or anticipation that such a live, attenuated vaccine will be required during the study. Live vaccines during the study and until participants' B- cells recover, are prohibited. Note: Influenza vaccination should be given during influenza season only. Participants must not receive live, attenuated influenza vaccine (e.g., FluMist) at any time during the study treatment period).
  • Use of any of the prohibited therapies including: investigational or unlicensed/unapproved agents; biologic agents (e.g., bevacizumab, erlotinib); immunotherapy/radio-immunotherapy; radiotherapy (with the exception of limited field palliative radiotherapy for bone pain or for soft tissue lesions after consultation with the Sponsor); chemotherapy (apart from Pola-R-CHP per protocol); hormone therapy (other than contraceptives, hormone-replacement therapy, or megestrol acetate); chronic use of steroids (inhaled, topical or systemic)
  • Positive test results for hepatitis B virus (HBV) infection (defined as positive B surface antigen [HBsAg] serology). Patients with occult or prior HBV infection (defined as negative HBsAg and positive hepatitis B core antibody [HBcAb]) may be included if HBV DNA is undetectable, provided that they are willing to undergo DNA testing on Day 1 of every cycle and every three months for at least 12 months after the last cycle of study treatment and appropriate antiviral therapy.
  • Positive test results for hepatitis C virus (HCV) antibody. Patients who are positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Absolute Neutrophil Count (ANC) <1.0 x109/L (subjects with bone marrow involvement by lymphoma are eligible regardless of ANC).
  • Hemoglobin (Hgb) ≤ 9 g/dL
  • Platelets <50 x109/L (subjects with bone marrow involvement by lymphoma are eligible regardless of platelet count)
  • Total serum bilirubin >2 times the upper limit of normal (or <3 times for Gilbert's disease or documented hepatic involvement by lymphoma), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >3 times the upper limit of normal (or >5 times for documented hepatic involvement by lymphoma)
  • Creatinine clearance <30 mL/min.
  • Prothrombin time (PT)/ international normalized ratio (INR) >2 times the upper limit of normal in the absence of anticoagulants or partial thromboplastin time (PTT) >2 times the upper limit of normal in the absence of anticoagulants.
  • Breastfeeding or pregnant, or intending to become pregnant during the study or within 12 months after the final dose of Pola-R-CHP, 3 months after the final dose of tocilizumab (if applicable), or 2 months after the final dose of glofitamab. WOCBP must have a serum pregnancy test done a maximum of 7 days prior to treatment initiation and a negative result must be documented prior to recruitment.
  • Concurrent participation in another therapeutic clinical trial.
  • 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.
  • Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot Marie Tooth disease.
  • Known history of progressive multifocal leukoencephalopathy.
  • Positive severe acute respiratory syndrome (SARS-CoV-2) test within 7 days prior to enrollment. Rapid antigen test result is also acceptable.
  • Known or suspected chronic active Epstein-Barr viral infection.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

John Kuruvilla, FRCPC contact

4169462821

LymphomaClinicalTrials@uhn.ca

Canada3 sites, 3 recruiting

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

    Chadi Zakaria, Ph.D., 514-340-8222 ext. 23293, chadi.zakaria.ccomtl@ssss.gouv.qc.ca

    Recruiting

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

    Not yet recruiting

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

    John Kuruvilla, 416-946-4501 x 2821, john.kuruvilla@uhn.ca

    Recruiting

Other trials in Canada

About this study

Official title: Feasibility Trial of Glofitamab in a Response Adapted Approach Incorporating Interim FDG PET and ctDNA to Optimize Primary Therapy of DLBCL

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

Read the detailed description

This is a multicenter, phase II, non-randomized, open-label, single-arm study in patients with untreated DLBCL. Patients will be on treatment for a total of 6 cycles, each 21 days in length.

After receiving 2 cycles of polatuzumab vedotin, cyclophosphamide, doxorubicin, prednisone (Pola-R-CHP), a risk-adapted approach will be used to modify therapy for patients who are found to be of an unfavourable risk. Pola-R-CHP chemotherapy will be administered every 21 days at standard doses: polatuzumab vedotin 1.8 mg/kg IV on day 1, cyclophosphamide 750 mg/m2 IV on day 1, doxorubicin 50 mg/m2 IV on day 1, prednisone 100 mg orally daily days 1-5, and rituximab 375 mg/m2 IV within 72 hours of polatuzumab vedotin and CHP. No subcutaneous administration of rituximab is allowed in this study.

All patients will undergo circulating tumour DNA (ctDNA) evaluation in peripheral blood at baseline and prior to cycle 2 of Pola-R-CHP. Interim response will also be assessed by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) scan response prior to cycle 3 of treatment positron emission tomography (PET2). Based on these tests, patients will be risk stratified into two treatment arms. The ctDNA low-risk patients (favourable ctDNA and PET2) will receive two additional cycles of Pola-R-CHP chemotherapy followed by 2 additional courses of rituximab. See Table 3 for exact treatment dosing for Cycles 3 - 6.

The ctDNA high-risk risk group (unfavourable ctDNA and/or PET2) will receive 4 additional cycles of Pola-R-CHP chemotherapy given with glofitamab. See Table 4 for exact treatment dosing for Cycles 3 - 6. Following six cycles of treatment, patients in both groups will undergo treatment assessment with CT scan, PET/CT scan, and bone marrow biopsy (as required).

Following completion of protocol treatment, patients will go into survival follow-up. Routine assessments will include patient visits with laboratory testing including ctDNA testing every 3 months. Imaging studies (PET/CT scan) will be repeated every 6 months.

Being tested
glofitamab
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • glofitamabDrug

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

Study groups in NCT06050694
Study groupRoleWhat they receive
Pola-R-CHPNo interventionProtocol 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 glofitamabExperimentalHigh-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
Receives: Drug: glofitamab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

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

Secondary outcomes (5)

  1. Event-free survival (EFS)

    To evaluate the event-free survival (EFS) of an iRAAp in primary therapy of DLBCL

    Measured: baseline to month 24

  2. Incidence of treatment emergent adverse events

    To evaluate the tolerability and toxicity of an iRAAp in primary therapy of DLBCL by assessing the frequency, severity, and relatedness of adverse events

    Measured: baseline to cycle 6 (each cycle is 21 days)

  3. Progression free survival (PFS) at 12 months and 24 months

    To assess PFS at 12-months and 24-months in the whole population and both ctDNA high-risk and ctDNA low-risk response cohorts.

    Measured: baseline to 24 months

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

    To evaluate changes in health-related quality of life (HRQOL) through treatment and follow-up. HRQOL inclusive of three validated patient-reported outcome (PRO) instruments (FACT-Lym, FACT-Cog and EORTC QLQ-C30) that will be completed by the participant at required visits. The FACT-Lym was designed to address health-related quality-of-life issues for patients with non-Hodgkin's lymphoma (NHL), and includes both general concerns related to cancer treatments and specific concerns relevant to lymphoma. The FACT-Cog is a well-validated tool that measures cognitive complaints. The EORTC QLQ-C30 includes 30 separate questions (items) resulting in 5 functional scales (Physical Functioning, Role Functioning, Emotional Functioning, Cognitive Functioning, and Social Functioning), 1 Global Health Status scale, 3 symptom scales (Fatigue, Nausea and Vomiting, and Pain), and 6 single items (Dyspnea, Insomnia, Appetite Loss, Constipation, Diarrhea, and Financial Difficulties).

    Measured: baseline through year 2

  5. Overall survival (OS) at 12 months and 24 months

    To assess OS at 12-months and 24 months in the whole population and both ctDNA high-risk and ctDNA low-risk response cohorts.

    Measured: baseline to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Sep 2023
  2. Study start24 Jan 2025
  3. Primary completionNov 2027 (estimated)
  4. Study completionNov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06050694
Sponsor's protocol ID
OZM-121
Acronym
GRAIL
Status last verified
Apr 2026
First submitted
29 Aug 2023
Last updated
24 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing glofitamab in people with Diffuse Large B Cell Lymphoma (DLBCL), run by University Health Network, Toronto at 3 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact John Kuruvilla, FRCPC (4169462821, LymphomaClinicalTrials@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To demonstrate the feasibility of a ctDNA and FDG-PET interim response adapted approach (iRAAp) for the primary therapy of DLBCL (time frame: At the end of cycle 1 (ctDNA) and cycle 2 (PET)(each cycle is 21 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06050694.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.

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