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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

Primary Purpose

Diffuse Large B-Cell Lymphoma (DLBCL)

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Glofitamab

Obinutuzumab

Tocilizumab

Rituximab

Ifosfamide

Carboplatin

Etoposide

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma (DLBCL)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Chao Family Comprehensive Cancer Center UCI
Memorial Cancer Institute at Memorial WestRecruiting
Tulane Medical Center; Investigational/Research PharmacyRecruiting
UMASS Memorial Medical CenterRecruiting
New York University Langone Medical CenterRecruiting
Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40Recruiting
MD Anderson Cancer CenterRecruiting
Medical College of WisconsinRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

R/R DLBCL

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Event-free survival (EFS) after enrollment

Progression-free survival (PFS) after enrollment

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

Overall survival (OS) after enrollment

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

Duration of Response (DOR)

Duration of complete response (DOCR)

Percentage of participants with adverse events (AEs)

Percentage of participants with cytokine release syndrome (CRS)

Maximum serum concentration (Cmax) of glofitamab

Minimum serum concentration (Cmin) of glofitamab

Percentage of participants with anti-drug antibodies (ADAs)

Full Information

NCT ID

NCT05364424

First Posted

May 3, 2022

Last Updated

October 3, 2023

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT05364424

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 4, 2022 (Actual)

Primary Completion Date

June 24, 2024 (Anticipated)

Study Completion Date

June 24, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diffuse Large B-Cell Lymphoma (DLBCL)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

R/R DLBCL

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Glofitamab

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Obinutuzumab

Intervention Description

Participants will receive IV obinutuzumab on Cycle 1 Day 1.

Intervention Type

Drug

Intervention Name(s)

Tocilizumab

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Rituximab

Intervention Description

Participants will receive up to 2 doses of IV rituximab.

Intervention Type

Drug

Intervention Name(s)

Ifosfamide

Intervention Description

Participants will receive IV ifosfamide for up to 3 cycles.

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

Participants will receive IV carboplatin for up to 3 cycles.

Intervention Type

Drug

Intervention Name(s)

Etoposide

Intervention Description

Participants will receive IV etoposide for up to 3 cycles.

Primary Outcome Measure Information:

Title

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

Time Frame

Up to 2.5 years

Secondary Outcome Measure Information:

Title

Event-free survival (EFS) after enrollment

Time Frame

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)

Title

Progression-free survival (PFS) after enrollment

Time Frame

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)

Title

Mobilization-adjusted response rate (MARR)

Description

Time Frame

Up to 2.5 years

Title

Overall survival (OS) after enrollment

Time Frame

From enrollment to death from any cause (up to 2.5 years)

Title

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

Time Frame

Up to 2.5 years

Title

Duration of Response (DOR)

Time Frame

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)

Title

Duration of complete response (DOCR)

Time Frame

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)

Title

Percentage of participants with adverse events (AEs)

Time Frame

Up to 2.5 years

Title

Percentage of participants with cytokine release syndrome (CRS)

Time Frame

Up to 2.5 years

Title

Maximum serum concentration (Cmax) of glofitamab

Time Frame

Up to 2.5 years

Title

Minimum serum concentration (Cmin) of glofitamab

Time Frame

Up to 2.5 years

Title

Percentage of participants with anti-drug antibodies (ADAs)

Time Frame

From baseline up to 2.5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Reference Study ID Number: GO43693 https://forpatients.roche.com/

Phone

888-662-6728

global-roche-genentech-trials@gene.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Chao Family Comprehensive Cancer Center UCI

City

Orange

State/Province

California

ZIP/Postal Code

92868

Country

United States

Individual Site Status

Active, not recruiting

Facility Name

Memorial Cancer Institute at Memorial West

City

Pembroke Pines

State/Province

Florida

ZIP/Postal Code

33028

Country

United States

Individual Site Status

Recruiting

Facility Name

Tulane Medical Center; Investigational/Research Pharmacy

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70112

Country

United States

Individual Site Status

Recruiting

Facility Name

UMASS Memorial Medical Center

City

Worcester

State/Province

Massachusetts

ZIP/Postal Code

01655

Country

United States

Individual Site Status

Recruiting

Facility Name

New York University Langone Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Individual Site Status

Recruiting

Facility Name

Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Individual Site Status

Recruiting

Facility Name

MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Name

Medical College of Wisconsin

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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