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 Eligible Diffuse B-Cell Lymphoma

• Status: Not yet recruiting
• Trial end date: 2024-10-22
• Target enrollment: 0
• Participant gender: All

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 eligible, defined as being medically eligible for intensive platinum-based salvage therapy followed by autologous stem cell transplantation (ASCT).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Carboplatin; Etoposide; Ifosfamide; Obinutuzumab; Rituximab

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

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

• Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better (with the exception of alopecia and anorexia, or as otherwise permitted by inclusion criteria)

• 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