GLORY: Glofit-GemOx With Liso-Cel For Lymphoma

NCT07711483 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 26-359
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to assess the clinical efficacy of bridging therapy with glofitamab/gemcitabine/oxaliplatin (Glofit-GemOx) followed by lisocabtagene maraleucel (liso-cel) in relapsed/refractory large B-cell lymphomas. This clinical trial also aims to investigate other efficacy parameters of the combination of Glofit-GemOx plus liso-cel and assess the safety of the combination of Glofit-GemOx bridging plus liso-cel. The main questions it aims to answer are:

• How effective Glofit-GemOx bridged to liso-cel therapy is compared to liso-cel alone?
• How will Glofit-GemOx bridged to liso-cel therapy affect other factors such as how long treatment effects last, how long patients survive after treatment, re-hospitalization rates, and more?
• How many patients receiving Glofit-GemOx bridging to liso-cel will experience side effects of differing severities? Participants will receive an obinutuzumab intravenous infusion 3 days prior to undergoing a leukapheresis procedure. 2 days after leukapheresis, participants will receive 1-2 cycles of Glofit-GemOx therapy via intravenous infusion. After completing Glofit-GemOx therapy, participants will receive lymphodepleting chemotherapy via intravenous infusion for 3 consecutive days, 3-5 days prior to then receiving an intravenous infusion of liso-cel.

Conditions

Lymphoma; B-cell Lymphomas; Relapsed/Refractory Large B-cell Lymphoma; Large B-cell Lymphoma

Keywords

GLORY; lymphoma; liso-cel; glofit-gemox; leukapheresis; CAR T-cell; bridging therapy

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CRR) to lisocabtagene maraleucel

  The complete response rate (CRR) is defined as the proportion of subjects achieving an objective response of complete response prior to start of another non-study anticancer therapy. CRR is based on the best overall response post-lisocabtagene maraleucel infusion. CRR will be defined according to the Lugano Classification.

  Screening to start of another non-study anticancer therapy or for up to 2 years from the day the last participant is enrolled, whichever occurs first.

Secondary Outcomes (14)

• Overall Response Rate to Glofit-GemOx bridging

  Screening to start of another non-study anticancer therapy or for up to 2 years from the day the last participant is enrolled, whichever occurs first.

• Progression-Free Survival (PFS) after lisocabtagene maraleucel

  Registration to death or up to 2 years after the day of the lisocabtagene maraleucel infusion.

• Overall Survival (OS) after lisocabtagene maraleucel

  Registration to death or up to 2 years after the day of the lisocabtagene maraleucel infusion.

• Overall Response Rate (ORR) to lisocabtagene maraleucel

  Screening to start of another non-study anticancer therapy or for up to 2 years from the day the last participant is enrolled, whichever occurs first.

• Duration of Response (DOR) after lisocabtagene maraleucel

  Day of first measurement meeting CR or PR criteria to the day of first documentation of recurrent or progressive disease or for up to 2 years after the day of the lisocabtagene maraleucel infusion.

Study Arms (1)

Liso-Cel after Glofit-GemOx bridging therapy

EXPERIMENTAL

Participants will receive obinutuzumab at the pre-determined dose 4 days prior to undergoing leukapheresis. After leukapheresis, participants will receive glofitamab, gemcitabine, and oxaliplatin (Glofit-GemOx) at the pre-determined doses over 3 weeks for 1-2 treatment cycles (each cycle is 21 days). Participants will then receive lymphodepleting chemotherapy of fludarabine and cyclophosphamide at the pre-determined doses for 3 consecutive days. Lsiocabtagene maraleucel (liso-cel) will be administered 2-7 days after the participants completes lymphodepleting chemotherapy.

Drug: Obinutuzumab; Drug: Glofitamab; Drug: Gemcitabine & oxaliplatin; Procedure: Leukapheresis; Drug: Lymphodepleting chemotherapy; Drug: LISOCABTAGENE MARALEUCEL

Interventions

Obinutuzumab DRUG

Intravenous infusion received once, 5 days prior to receiving the first doses of glotfitamab, gemcitabine, and oxaliplatin.

Also known as: GA101, RO5072759

Liso-Cel after Glofit-GemOx bridging therapy

Glofitamab DRUG

Intravenous infusion received on days 1, 3, 8, and 15 of cycle 1 and on day 15 of the optional cycle 2 (each cycle is 21 days).

Liso-Cel after Glofit-GemOx bridging therapy

Gemcitabine & oxaliplatin DRUG

Intravenous infusions received on day 1 of cycle 1 and an optional cycle 2 (each cycle is 21 days).

Liso-Cel after Glofit-GemOx bridging therapy

Leukapheresis PROCEDURE

Procedure to collect stem cells for modification that will occur 2 days prior to administration of the first doses of glofitamab, gemcitabine, and oxaliplatin.

Liso-Cel after Glofit-GemOx bridging therapy

LISOCABTAGENE MARALEUCEL DRUG

Intravenous infusion of participant's re-manufactured stem cells administered one 3-5 days after completing lymphodepleting chemotherapy.

Liso-Cel after Glofit-GemOx bridging therapy

Lymphodepleting chemotherapy DRUG

Intravenous infusions of cyclophosphamide and fludarabine administered for 3 consecutive days 3-5 days prior to receive lisocabtagene maraleucel.

Also known as: cyclophosphamide, fludarabine

Liso-Cel after Glofit-GemOx bridging therapy

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed large B-cell NHL including diffuse large B-cell lymphoma (DLBCL), either de novo or transformed from any indolent B-cell lymphoma, DLBCL NOS, primary mediastinal \[thymic\] large B-cell lymphoma (PMBCL), high grade B-cell lymphoma NOS, or high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements \[double/triple-hit lymphoma (DHL/THL)\]; and grade 3B follicular lymphoma.
• Relapsed or refractory to 1 prior line of systemic lymphoma therapy if relapse/refractory within 12 months of initial treatment. Previous therapy must have included a CD20-targeted agent and an anthracycline or alkylating agent. Patients may have received steroids and/or polatuzumab-rituximab (without bendamustine), and/or radiation therapy for disease control and/or palliation "holding therapy" between frontline therapy and protocol registration and this will not be considered an additional line of systemic therapy.
• OR Relapsed or refractory to 1 prior line of systemic lymphoma therapy at any time after initial treatment if patient is ineligible for a stem cell transplant. Previous therapy must have included a CD20-targeted agent and an anthracycline or alkylating agent. Patients may have received steroids and/or polatuzumab-rituximab (without bendamustine), and/or radiation therapy for disease control and/or palliation "holding therapy" between frontline therapy and protocol registration and this will not be considered an additional line of systemic therapy.
• Intent and eligibility to proceed to therapy with lisocabtagene maraleucel
• Adult patients ≥ 18 years
• PET-positive measurable disease per Lugano criteria
• ECOG performance status 0-2
• Estimated creatinine clearance of ≥30 mL/min, calculated using the Cockcroft and Gault equation (if male: \[140 - Age\] x Mass \[kg\] / \[72 x creatinine g/dL\]; multiply by 0.85 if female)
• Serum Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 3 times the ULN
• Total Bilirubin ≤1.5 x ULN, unless directly attributable to Gilbert-Meulengracht syndrome and ≤3.0 mg/dL
• Absolute neutrophil count (ANC) ≥ 1000/mm3 (G-CSF support allowed if ≥ 24 hours prior to screening lab draw)
• Hemoglobin ≥8g/dL
• Platelets ≥ 50,000/mm3 without transfusion within 7 days
• Patients with primary CNS lymphoma are not eligible. Patients with secondary CNS involvement by lymphoma are eligible if they otherwise meet all eligibility criteria.
• The effects of glofitamab, gemcitabine, and oxaliplatin on the developing human fetus are unknown. For this reason and because immunotherapy/chemotherapy agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate double-method (each partner) contraception (acceptable means of birth control: condoms (male), condoms (female), intrauterine devices, contraceptive implants, combined hormonal contraceptives (pills, patches, vaginal rings), progestin-only pills, depot medroxyprogesterone acetate (DMPA) injections; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation, and 12 months after completion of lisocabtagene maraleucel administration.

You may not qualify if:

• History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following: Non-melanoma skin cancers, in situ malignancies, prostate cancer followed with watchful waiting, indolent lymphoma, any previously treated malignancy felt at low risk for recurrence.
• Evidence of disease (such as severe or uncontrolled systemic diseases) that, in the investigator's opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol
• Treatment with prior CAR T-cell therapy.
• Treatment with prior CD20:CD3 bispecific antibody therapy.
• History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
• Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
• Received a live virus vaccination within 28 days of first dose of study drug.
• Concurrent participation in another therapeutic clinical trial.
• Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk
• Previous treatment with gene therapy product or adoptive T cell therapy
• Allogeneic stem cell transplant within 90 days of leukapheresis
• Active acute or chronic GVHD requiring immunosuppressive therapy within 6 weeks prior to enrollment
• Grade 2 or higher peripheral neuropathy
• Serologic status reflecting active hepatitis B or C infection
• Subjects who are hepatitis B core antibody (HBcAb) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative PCR result before enrollment and must be willing to undergo DNA PCR testing during the study and take anti-HBV therapy with entecavir or equivalent. Those who are HBsAg-positive or hepatitis B PCR positive will be excluded.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, B-Cell; Recurrence

Interventions

obinutuzumab; glofitamab; gemcitabine-oxaliplatin regimen; Leukapheresis; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Jeremy Abramson, MD, MMSc

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeremy Abramson, MD, MMSc

CONTACT

617-726-8566; jabramson@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 17, 2026
• Study Start (Estimated): October 14, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2030
• Last Updated: July 17, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)