A Study of Glofitamab-based Treatment in People With Diffuse Large B-cell Lymphoma

NCT06765317 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 24-332
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 7

Brief Summary

The researchers are doing this study to find out if the study treatment is an effective treatment that causes few or mild side effects in people with diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), or transformed lymphoma. The treatment being tested in this study is glofitamab, polatuzumab, and obinutuzumab in combination with standard treatment (the combination of rituximab, cyclophosphamide, doxorubicin, and prednisone, or R-miniCHP).

Conditions

Diffuse Large B Cell Lymphoma (DLBCL); High Grade B Cell Lymphoma

Keywords

Glofitamab; Polatuzumab; Obinutuzumab; Rituximab; Cyclophosphamide; Doxorubicin

Outcome Measures

Primary Outcomes (1)

• evaluate the complete response rate (CRR)

  according to the 2014 Lugano Response Criteria

  1 year

Study Arms (1)

Obinutuzumab, Glofitamab and Polatuzumab

EXPERIMENTAL

All patients will receive 2 cycles of glofitamab and polatuzumab followed by an interim PET scan (iPET2). If iPET2 is negative (Deauville score 1-3), patients will receive 4 cycles of glofitamab-polaRminiCHP. If iPET is positive (Deauville score 4,5) with partial response or stable disease, patients will receive 6 cycles of glofitamab-pola-R-miniCHP (polatuzumab will be omitted from last 2 cycles to keep total number of doses at 6 per standard of care)

Drug: Glofitamab; Drug: Polatuzumab; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Obinutuzumab:

Interventions

Glofitamab DRUG

C1D8 2.5 mg iv; C1D15 10 mg iv; C2D1-onwards: 30 mg iv, every 3 weeks

Obinutuzumab, Glofitamab and Polatuzumab

Polatuzumab DRUG

1.8 mg/kg iv C1D1 onwards, every 3 weeks

Obinutuzumab, Glofitamab and Polatuzumab

Rituximab DRUG

375 mg/m2 iv D1

Obinutuzumab, Glofitamab and Polatuzumab

Cyclophosphamide DRUG

400 mg/m2 iv D1

Obinutuzumab, Glofitamab and Polatuzumab

Doxorubicin DRUG

25 mg/m2 iv D1

Obinutuzumab, Glofitamab and Polatuzumab

Obinutuzumab: DRUG

1000 mg iv C1D1 (7 days prior to glofitamab administration) single dose

Obinutuzumab, Glofitamab and Polatuzumab

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 65-79 years with a fitness assessment of unfit or frail per simplified GA (Appendix 1, www.filinf.it/epi)
• Age ≥80 years with any fitness level
• Pathologically confirmed DLBCL, HGBCL or transformed lymphoma
• No prior systemic anti-lymphoma therapy (prednisone/equivalent up to 100 mg daily x 7 days is permissible)
• Ann Arbor Stage 2 bulky, 3 or 4 disease (Appendix 1)
• Any IPI score (Appendix 1)
• Anthracycline eligible: LVEF ≥ 45% by echocardiogram or MUGA scan.
• Must have at least one bi-dimensionally measurable lesion (\>1.5 cm in its largest dimension for nodal lesions, or \>1.0 cm in its largest dimension for extranodal lesions by computerized tomography \[CT\] scan or MRI)
• Eastern Cooperative Oncology Group performance status ≤ 2 (Appendix 1)
• Must have adequate organ and marrow status:
• Absolute neutrophil count (ANC) ≥1,000/mm3 or ≥500/mm3 if due to disease involvement in the bone marrow
• Platelet count ≥50,000 cells/mm3 or ≥25,000/mm3 if due to disease involvement in the bone marrow
• Patients who do not meet criteria for bone marrow function due to marrow involvement of lymphoma and/or other disease-related cytopenias (e.g., immune thrombocytopenia) may be enrolled into the study after discussion with, and confirmation by the PI.
• Serum creatinine ≤ULN OR estimated Creatinine Clearance (CrCl) ≥30 mL/min (Cockcroft-Gault formula or other institutional standard methods)
• Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤3 x upper limit of normal (ULN)

You may not qualify if:

• Prior systemic anti-lymphoma therapy (localized radiation, steroids and antibiotics are permitted)
• Prior solid organ transplantation
• Prior allogeneic stem cell transplantation
• Active CNS involvement
• Uncontrolled HIV or active HBV or HCV infection (controlled HIV with undetectable viral load and previously treated HBV and HCV are allowed) 5.1 Participants with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) DNA is undetectable at the time of screening. Such participants must be willing to undergo HBV DNA testing on Day 1 of every cycle and every 3 months for at least 12 months after the final cycle of study treatment and appropriate antiviral therapy as indicated.
• Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
• Uncontrolled active systemic infection
• Major surgery within 4 weeks of the first dose of study drug (exceptions may be allowed after discussion with PI if patient has fully recovered from procedure and antilymphoma therapy is urgently needed)
• Significant or extensive history of 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 3 months prior to the start of Cycle 1, unstable arrhythmias, or unstable angina.
• Uncontrolled autoimmune disorder
• A history of confirmed progressive multifocal leukoencephalopathy
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or risk study outcomes
• Inability to comply with all the study-related procedures, in the investigator's judgement.
• Contraindication to any of the individual components of polatuzumab, R-miniCHP and glofitamab or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
• Prior treatment with systemic immunotherapeutic agents, including but not limited to, radio-immuno-conjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (mAbs) (e.g., anti-cytotoxic T lymphocyte associated protein 4, anti-PD-1, and anti-PD-L1) within 4 weeks or five half-lives of the drug, whichever is shorter 15. Prior use of any monoclonal antibody for the purposes of treating cancer within 3 months of the start of Cycle 1

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Cancer Center Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Rockville Centre, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

glofitamab; polatuzumab vedotin; Rituximab; Cyclophosphamide; Doxorubicin; obinutuzumab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Pallawi Torka, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pallawi Torka, MD

CONTACT

201-775-7808; torkap@mskcc.org

Paul Hamlin, MD

CONTACT

646-608-3706

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2025
• First Posted: January 9, 2025
• Study Start: January 16, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (7)