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

Diffuse Large B-Cell Lymphoma (DLBCL) Clinical Trial

Official title:

A Phase IB, Open-Label, Multicenter, Single Arm Study Evaluating the Preliminary Efficacy, Safety, and Pharmacokinetics of Glofitamab in Combination With Rituximab Plus Ifosfamide, Carboplatin Etoposide Phosphate in Patients With Relapsed/Refractory Transplant or CAR-T Therapy Eligible Diffuse B-Cell Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05364424
• Other study ID #: GO43693
• Status: Recruiting
• Phase: Phase 1
• Start date: November 4, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: GO43693 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma (DLBCL)
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Glofitamab
Participants will receive intravenous (IV) glofitamab for up to 3 cycles.
• Obinutuzumab
Participants will receive IV obinutuzumab on Cycle 1 Day 1.
• Tocilizumab
Participants will receive IV tocilizumab as necessary to manage cytokine release syndrome (CRS) events.
• Rituximab
Participants will receive up to 2 doses of IV rituximab.
• Ifosfamide
Participants will receive IV ifosfamide for up to 3 cycles.
• Carboplatin
Participants will receive IV carboplatin for up to 3 cycles.
• Etoposide
Participants will receive IV etoposide for up to 3 cycles.

Locations

Country	Name	City	State
United States	The University of Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40	Cleveland	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Tulane Medical Center; Investigational/Research Pharmacy	New Orleans	Louisiana
United States	New York University Langone Medical Center	New York	New York
United States	Chao Family Comprehensive Cancer Center UCI	Orange	California
United States	Memorial Cancer Institute at Memorial West	Pembroke Pines	Florida
United States	UMASS Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR), defined as the proportion of participants that achieves a CR or PR within three cycles of glofit-R-ICE, as determined by the investigator according to Lugano criteria		Up to 2.5 years
Secondary	Event-free survival (EFS) after enrollment		From enrollment to the first occurrence of disease progression, initiation of new anti-lymphoma therapy (not including planned ASCT or CAR-T therapy), or death from any cause (whichever occurs first) (up to 2.5 years)
Secondary	Progression-free survival (PFS) after enrollment		From enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) as determined by the investigator according to Lugano criteria (up to 2.5 years)
Secondary	Mobilization-adjusted response rate (MARR)	The proportion of participants treated with intent to proceed to ASCT that achieves a CR or PR within three cycles of glofit-R-ICE, as determined by the investigator according to Lugano criteria, and additionally achieves mobilization of a minimum of 2,000,000 CD34+ hematopoietic stem cells/kg for ASCT	Up to 2.5 years
Secondary	Overall survival (OS) after enrollment		From enrollment to death from any cause (up to 2.5 years)
Secondary	CR rate after enrollment, defined as the proportion of participants that achieves a CR within three cycles of glofit-R-ICE, as determined by the investigator according to Lugano criteria		Up to 2.5 years
Secondary	Duration of Response (DOR)		From the first occurrence of a documented objective response (CR or PR) to disease progression or death from any cause (whichever occurs first) as determined by the investigator according to Lugano criteria (up to 2.5 years)
Secondary	Duration of complete response (DOCR)		From the first occurrence of a documented complete response to disease progression or death from any cause (whichever occurs first) as determined by the investigator according to Lugano criteria (up to 2.5 years)
Secondary	Percentage of participants with adverse events (AEs)		Up to 2.5 years
Secondary	Percentage of participants with cytokine release syndrome (CRS)		Up to 2.5 years
Secondary	Maximum serum concentration (Cmax) of glofitamab		Up to 2.5 years
Secondary	Minimum serum concentration (Cmin) of glofitamab		Up to 2.5 years
Secondary	Percentage of participants with anti-drug antibodies (ADAs)		From baseline up to 2.5 years