A Study Evaluating the Efficacy, Safety, and Pharmacokinetics of Glofitamab in Combination With Rituximab Plus Ifosfamide, Carboplatin Etoposide Phosphate in Participants With Relapsed/Refractory Transplant or CAR-T Therapy Eligible Diffuse B-Cell Lymphoma

NCT ID: NCT05364424

Last Updated: 2025-12-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-04
• Study Completion Date: 2025-10-15

Brief Summary

The purpose of this study is to evaluate the preliminary efficacy, safety, and pharmacokinetics of glofitamab (glofit) in combination with rituximab plus ifosfamide, carboplatin, and etoposide (R-ICE) in participants with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), who have failed one prior line of therapy incorporating an anti-cluster of differentiation (CD) 20 antibody (i.e., rituximab) and an anthracycline, and who are transplant or chimeric antigen receptor T-cell (CAR-T) therapy eligible, defined as being medically eligible for intensive platinum-based salvage therapy followed by autologous stem cell transplantation (ASCT) or for CAR-T therapy.

Conditions

Diffuse Large B-Cell Lymphoma (DLBCL)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R/R DLBCL

Participants will receive up to 3 21-day cycles of glofitamab, rituximab, ifosfamide, carboplatin, and etoposide (glofit-R-ICE).

Group Type: EXPERIMENTAL

Glofitamab

Intervention Type: DRUG

Participants will receive intravenous (IV) glofitamab for up to 3 cycles.

Obinutuzumab

Intervention Type: DRUG

Participants will receive IV obinutuzumab on Cycle 1 Day 1.

Tocilizumab

Intervention Type: DRUG

Participants will receive IV tocilizumab as necessary to manage cytokine release syndrome (CRS) events.

Rituximab

Intervention Type: DRUG

Participants will receive up to 2 doses of IV rituximab.

Ifosfamide

Intervention Type: DRUG

Participants will receive IV ifosfamide for up to 3 cycles.

Carboplatin

Intervention Type: DRUG

Participants will receive IV carboplatin for up to 3 cycles.

Etoposide

Intervention Type: DRUG

Participants will receive IV etoposide for up to 3 cycles.

Interventions

Glofitamab

Participants will receive intravenous (IV) glofitamab for up to 3 cycles.

Intervention Type: DRUG

Obinutuzumab

Participants will receive IV obinutuzumab on Cycle 1 Day 1.

Intervention Type: DRUG

Tocilizumab

Participants will receive IV tocilizumab as necessary to manage cytokine release syndrome (CRS) events.

Intervention Type: DRUG

Rituximab

Participants will receive up to 2 doses of IV rituximab.

Intervention Type: DRUG

Ifosfamide

Participants will receive IV ifosfamide for up to 3 cycles.

Intervention Type: DRUG

Carboplatin

Participants will receive IV carboplatin for up to 3 cycles.

Intervention Type: DRUG

Etoposide

Participants will receive IV etoposide for up to 3 cycles.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Life expectancy ≥ 12 weeks
• Histologically confirmed B-cell lymphoma
• One line of prior systemic therapy including an anti-CD20 monoclonal antibody (i.e. rituximab) and an anthracycline
• Relapsed or refractory disease after first-line chemoimmunotherapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Participant must be a candidate for high-dose chemotherapy followed by ASCT or CAR-T therapy

• Prior solid organ transplantation
• Prior allogeneic stem cell transplant
• Prior ASCT for lymphoma
• Prior autologous stem cell transplant for any indication other than lymphoma, within 5 years from the start of study treatment
• Active autoimmune disease requiring treatment
• Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 4 weeks prior to first dose of study treatment
• Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Participants who received corticosteroid treatment with ≤ 30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to Cycle 1 Day 1. Participants may have received a brief (≤ 7 days) course of systemic steroids (≤ 100 mg prednisone equivalent per day) prior to initiation of study therapy for control of lymphoma-related symptoms
• Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
• Clinically significant history of cirrhotic liver disease

Exclusion Criteria

• Treatment with more than one prior line of therapy for DLBCL
• Primary mediastinal B-cell lymphoma
• Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
• Peripheral neuropathy assessed to be Grade > 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 at enrollment
• Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
• Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment
• Primary or secondary CNS lymphoma at the time of enrollment or history of CNS lymphoma
• Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Known history of progressive multifocal leukoencephalopathy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Chao Family Comprehensive Cancer Center UCI

Orange, California, United States

Memorial Cancer Institute at Memorial West

Pembroke Pines, Florida, United States

The University of Chicago

Chicago, Illinois, United States

Tulane Medical Center

New Orleans, Louisiana, United States

UMASS Memorial Medical Center

Worcester, Massachusetts, United States

New York University Langone Medical Center

New York, New York, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

MD Anderson Cancer Center

Houston, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

GO43693

Identifier Type: -

Identifier Source: org_study_id