Glofitamab Versus Investigator's Choice in Patients with Relapsed or Refractory Mantle Cell Lymphoma
- Trial ID
- 2023-503206-37-00
- Protocol
- GO43878
- Sponsor
- F. Hoffmann-La Roche AG
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the efficacy of glofitamab monotherapy compared to an investigator's choice of bendamustine with rituximab or lenalidomide with rituximab in patients with relapsed/refractory mantle cell lymphoma, specifically regarding progression-free survival. 5
Secondary objectives include the assessment of:
- Efficacy endpoints such as complete response rate, objective response rate, and overall survival.
- Additional efficacy measures including investigator-assessed and blinded independent central review (BIRC)-assessed duration of response, duration of complete response, and event-free survival.
- Safety and tolerability profiles.
- Health-related quality of life, including time to deterioration in lymphoma symptoms and improvements in physical functioning or fatigue.
- Pharmacokinetic characterization of glofitamab.
- The immune response to the study drug.
Participants
This study involves 137 participants diagnosed with mantle cell lymphoma. The study population includes both male and female individuals. Participants must have relapsed or refractory disease that has been histologically confirmed via cyclin D1 overexpression or the presence of the t(11:14) translocation. Inclusion requires at least one prior line of systemic therapy, specifically including a Bruton tyrosine kinase inhibitor in combination with another systemic treatment. Eligible subjects must demonstrate PET-positive disease at screening according to the Lugganau Classification. Furthermore, participants are required to have adequate hematologic function and renal function, defined by an estimated creatinine clearance of at least 30 mL/min.
Plans and Procedures
This Phase III, open-label, multicenter, randomized study is designed to evaluate the efficacy of glofitamab as a single agent compared to an investigator's choice of therapy in patients with relapsed/refractory mantle cell lymphoma. The primary objective is to assess progression-free survival as determined by a blinded independent review committee. The comparator arms consist of either bendamustine with rituximab or lenalidomide with rituximab. Study participation begins with a screening visit to confirm histological diagnosis, PET-positive disease, and adequate renal and hematologic function. Following randomization, participants will undergo treatment and subsequent follow-up assessments to monitor overall survival, response rates, and safety parameters, including the incidence of cytokine-release syndrome. The trial is expected to continue through 2026. Early termination from the study may occur based on clinical criteria or investigator discretion.
Treatment
Glofitamab is administered as a solution for infusion via intravenous infusion at a dose of 30 mg.
Obinutuzumab is administered as a solution for infusion via intravenous infusion at a dose of 1000 mg.
Tocilizumab is administered as a solution for infusion via intravenous infusion at a dose of 8 mg/kg.
Bendamustine hydrochloride is administered as a solution for infusion via intravenous infusion at a dose of 90 mg/m2.
Lenalidomide is administered as a hard capsule via oral administration at a dose of 20 mg.
Rituximab is administered as a solution for infusion via intravenous infusion at a dose of 375 mg/m2.
Efficacy
The primary efficacy endpoint is progression-free survival (PFS), which is determined by a Blinded Independent Review Committee (BIRC). Secondary endpoints include the complete response (CR) rate, overall response rate (ORR), overall survival (OS), duration of response (DOR), and duration of complete response (DOCR), as assessed by the BIRC. Additional investigator-assessed secondary endpoints consist of PFS, CR rate, OR rate, DOCR, DOR, and event-free survival (EFS).
Efficacy assessments also include evaluations of quality of life and symptom management. Parameters include the time to deterioration in physical functioning and fatigue, as well as the proportion of participants experiencing clinically meaningful improvements in physical functioning, fatigue, or lymphoma symptoms. These metrics are measured using the European Organization for Research and Treatment of Cancer (EORTC) quality of life (QoL)-C30 and the Functional Assessment of Cancer Therapy (FACT) Lymphoma Subscale (FACT-Lym LYMS) questionnaire. Furthermore, the proportion of participants reporting response options for the General Population, Question 5 (GP5) from the FACT-G is analyzed.
Pharmacokinetic and immunological parameters are monitored, specifically the serum concentration of glofitamab at specified timepoints and the prevalence or incidence of anti-drug antibodies (ADAs).
Inclusion and Exclusion Criteria
Inclusion Criteria
- PET-positive disease at screening (Deauville score of 4 or 5) according to the “Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification” with at least one target FDG-avid lesion In rare cases of non-FDG-avid MCL with at least one measurable lesion located in an area suitable for biopsy, such as the gastrointestinal tract and a biopsy can be obtained to confirm a histological diagnosis, a participant may be eligible
- Histologically-confirmed MCL, demonstrating either overexpression of cyclin D1 or the presence of t(11:14) within 12 months of study entry
- Relapsed or refractory disease
- At least one (>= 1) line of prior systemic therapy: - Inclusion of BTK inhibitor Prior therapy must have included a BTK inhibitor plus another systemic therapy option (e.g., a regimen containing a CD20 monoclonal antibody, prior chemotherapy, targeted agent therapy such as bortezomib, etc.) – Progression or Relapse: Participants must have progressed or relapsed at any time on BTK inhibitor therapy, or failed to achieve a partial response (PR) within 12 weeks of BTK inhibitor therapy – Exclusion of BTK Inhibitor Intolerance: Participants intolerant to BTK inhibitor therapy who are unable to complete at least 12 weeks of BTK inhibitor therapy should be excluded – Local Therapies: Local therapies (e.g., radiotherapy) will not be considered as lines of therapy
- Adequate renal function, defined as an estimated creatinine clearance ≥ 30 mL/min
- Adequate hematologic function
Exclusion Criteria
- History of other malignancy that could affect compliance with the protocol or interpretation of results - Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the compliance of or safety or efficacy assessment of the investigational regimen are eligible for this study
- Leukemic, non-nodal MCL
- Prior solid organ transplantation, prior allogeneic stem cell transplant
- Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3 and also treatment with chimeric antigen receptor T-cell (CAR-T) cell therapy
- Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma
- Presence of severe active bacterial, viral, fungal, mycobacterial, parasitic, or other infections at the time of study enrolment. Participants must have recovered from any severe or potentially serious infection (as assessed by the investigator) at least 2 weeks before the first study treatment
- Clinically significant history of cirrhotic liver disease
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 18 Dec 2023 | 10 |
 Italy | Recruiting | 18 Dec 2023 | 10 |
 Spain | Recruiting | 18 Dec 2023 | 12 |
 Sweden | Recruiting | 18 Dec 2023 | 7 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Bendamustin cell pharm® 2,5 mg/ml Pulver für ein Konzentrat zur Herstellung einer Infusionslösung | Comparator | PULVER FÜR EIN KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | IV INFUSION | 90 | 168 | PRD3489660 |
Lenalidomide Accord 5 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 20 | 252 | PRD6773394 |
Lenalidomide Accord 20 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 20 | 252 | PRD6773400 |
Bendamustin Hikma 2,5 mg/ml Pulver für ein Konzentrat zur Herstellung einer Infusionslösung | Comparator | PULVER FÜR EIN KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | IV INFUSION | 90 | 168 | PRD7979464 |
RoActemra 20 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | IV INFUSION | 8 | 1 | PRD2154623 |
Columvi 10 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | IV INFUSION | 30 | 252 | PRD10561232 |
Glofitamab | Test | SOLUTION FOR INFUSION | IV INFUSION | 30 | 252 | PRD9870862 |
RoActemra 20 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | IV INFUSION | 8 | 1 | PRD2154622 |
Lenalidomide Accord 15 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 20 | 252 | PRD6773399 |
Bendamustin Baxter 2,5 mg/ml Pulver für ein Konzentrat zur Herstellung einer
Infusionslösung | Comparator | PULVER FÜR EIN KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | IV INFUSION | 90 | 168 | PRD7977086 |