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
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma (DLBCL)
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
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
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
No
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
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
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
No
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
Email
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).
Learn more about this trial
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
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