Glofitamab Combined With Lenalidomide in High Risk Patients With Relapsed or Refractory Mantle Cell Lymphoma

A Single-arm, Open-label, Multi-center Clinical Study of Glofitamab Combined With Lenalidomide in High Risk Patients With Relapsed or Refractory Mantle Cell Lymphoma Previously Treated With a BTK Inhibitor

A single-arm, open-label, multi-center clinical study of glofitamab combined with lenalidomide in high risk patients with relapsed or refractory Mantle Cell Lymphoma previously treated with a BTK Inhibitor.

Patients will be eligible if they have received one or more prior lines of therapy, one of which must have been a BTKi. Patients will be enrolled according to a Simon two-stage design, with early stop criteria for lack of efficacy.

Glofitamab will be administered intravenously and lenalidomide will be self-administered orally.

Obinutuzumab pretreatment will be administered intravenously as 2 doses of 1000 mg prior to glofitamab initiation. The primary endpoint is BOR at the end of induction, evaluated by PET/CT according to Lugano criteria during study enrolment.

The primary objective is to evaluate the best objective response rate (BOR) at the end of induction of the combination of glofitamab and lenalidomide.

Study Overview

• Status: Recruiting
• Conditions: MCL; Relapsed or Refractory Mantle Cell Lymphoma (MCL)
• Intervention / Treatment: Drug: Glofitamab; Drug: Lenalidomide

Detailed Description

The goal of this clinical study is to evaluate the efficacy of glofitamab combined with lenalidomide in high-risk patients with R/R MCL previously treated with a BTK Inhibitor. The main questions it aims to answer are:

1. the efficacy of glofitamab combined with lenalidomide in high-risk patients with R/R MCL by best overall response rate (BOR) at the end of induction.
2. the efficacy of glofitamab combined with lenalidomide in Chinese high-risk patients with R/R MCL, including complete response rate (CRR) at C6 and the end of induction, overall response rate at C6 and the end of induction, best response of complete response (BOCR) .
3. the safety profiles of Glofitamab combined with lenalidomide in the treatment of high-risk mantle cell lymphoma.
4. the potential biomarkers which can predict efficacy and safety of Glofitamab combined lenalidomide in Chinese adult patients with relapsed/refractory high risk mantle cell lymphoma, including circulating tumor DNA (ctDNA), total metabolic tumor volume (TMTV), etc.

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hongmei Jing; Phone Number: 86 010-82266781; Email: hongmei_jing@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100191
      • Recruiting
      • Peking University Third Hospital
      • Contact: Hongmei Jing; Phone Number: 010-82266778; Email: hongmei_jing@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• • Signed Informed Consent Forms

  • Age: >= 18 to 80 years
  • Eastern Cooperative Oncology Group =< 2
  • Diagnosis of MCL established by histologic assessment
  • Previously treated with at least one prior line of systemic therapy for mantle cell lymphoma.
  • Prior therapy have included a BTK inhibitor, including ibrutinib, zanubrutinib, obrutinib, acalabrutinib and various BTKi in clinical trials. BTki exposure is required, which include BTKi failure or intolerance. BTKi failure is defined as progression of disease during BTKi therapy or patients have progressed or relapsed after completing BTK inhibitor therapy

  • At least one high risk features as classified:

    • Blastoid/pleomorphic variants ✔ Ki67 ≥50% ✔ TP53 mutation or deletion
    • Bulky disease (defined as any lesion ≥7.5 cm on the screening computed tomography [CT] scan）
    • Patients that did not achieve a CR with their first-line treatment
    • early disease progression (POD24) ✔ patients with relapse and refractory treatment above 3 lines
  • Measurable lesions on cross-sectional imaging documented by diagnostic imaging(MRI, CT or PET-CT), （GTD）≥1.5 cm
  • Adequate liver function : Total bilirubin =< 3 x upper limit of normal (ULN) (unless has Gilbert's disease), Aspartate aminotransferase (AST) =< 5.0 x ULN, Alanine aminotransferase (ALT) =< 5.0 x ULN

Exclusion Criteria:

• • Already enrolled in other Ongoing interventional or non-interventional R/R MCL clinical trials;

  • Currently receiving immunosuppressive treatment for other diseases;
  • Previous treatment with lenalidomide;
  • Combined with other malignant tumors within 3 years;
  • The researcher determines that they are not suitable to participate in this study;
  • Serious mental or neurological disorders that affect informed consent and/or the expression or observation of adverse reactions;
  • Have a history of major or extensive cardiovascular disease, such as New York Heart Association class III or Grade IV heart disease or objective assessment, myocardial infarction, unstable arrhythmia or unstable angina within 6 months before the first cycle;
  • Recent major surgery (within 4 weeks before the start of the first cycle);
  • Active autoimmune diseases with poor treatment control;
  • Any active infection that may affect the safety of the participant, including bacterial, fungal and various viral infections, occurred within 7 days before the first day of cycle 1;
  • Positive SARS-CoV-2 PCR test within 7 days prior to enrollment
  • Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HBsAg] serology) Participants with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) DNA is undetectable at the time of screening. Such participants must be willing to undergo HBV DNA testing on Day 1 of every cycle and every 3 months for at least 12 months after the final cycle of study treatment and appropriate antiviral therapy as indicated.
  • Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing) Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • A history of severe deep vein thrombosis event or pulmonary embolism within 6 months
  • Patient follow-up was not possible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: high risk patients with relapsed or refractory Mantle Cell Lymphoma previously treated with a BTKi; At least one high risk features as classified: Blastoid/pleomorphic variants ✔ Ki67 ≥50% ✔ TP53 mutation or deletion; Bulky disease (defined as any lesion ≥7.5 cm on the screening computed tomography [CT] scan）; Patients that did not achieve a CR with their first-line treatment; early disease progression (POD24) ✔ patients with relapse and refractory treatment above 3 lines

Drug: Glofitamab; Glofitamab is a human IgG1-bispecific antibody targeting CD20 expressed on the surface of B cells and CD3ɛ chain expressed on the surface of T cells.; Drug: Lenalidomide; Lenalidomide is an agent with immunomodulatory and anti-angiogenic properties which confer multiple antitumor effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to evaluate the efficacy of glofitamab combined with lenalidomide in high-risk patients with R/R MCL by best overall response rate (BOR) at the end of induction.	to evaluate the efficacy of glofitamab combined with lenalidomide in high-risk patients with R/R MCL by best overall response rate (BOR) at the end of induction, defined as the percent of patients who achieve a best complete response (CR) or partial response (PR) according to the 2014 Lugano response criteria for non-Hodgkin lymphoma at the end of induction.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR, defined as the proportion of patients with overall response rate at C6 and the end of induction, as determined by the investigator using 2014 Lugano Response Criteria.	up to 24 months
complete response rate (CRR)	CRR, defined as the proportion of patients with complete response rate（CRR）at C6 and the end of induction, and a best overall response of CR at any time during the studas determined by the investigator using 2014 Lugano Response Criteria.	Up to 24 months
Duration of Response (DoR)	DoR, defined as the time from the first occurrence of a documented objective response (PR or CR) to disease progression or death from any cause (whichever occurs first) according to the 2014 Lugano Response Criteria, as determined by the investigator.	Up to 48 months
Duration of Complete Response (DoCR)	DoCR, defined as the time from the initial occurrence of a documented CR until documented disease progression or death due to any cause, whichever occurs first according to the 2014 Lugano Response Criteria, as determined by the investigator.	Up to 48 months
Progression-Free Survival (PFS)	PFS, defined as the time from the first study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator using 2014 Lugano Response Criteria.	Up to 48 months
Overall Survival (OS)	OS, defined as the time from the first study treatment to the date of death from any cause.	Up to 48 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety profiles of Glofitamab combined with lenalidomide in the treatment of high-risk mantle cell lymphoma	List the number and frequency of hematological and non-hematological toxicity (NCI CTCAE v5.0) and calculate the incidence rate.	48 months

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: February 15, 2025
• First Submitted That Met QC Criteria: March 5, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Relapsed or Refractory MCL, previously treated with a BTK Inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, Mantle-Cell; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; glofitamab
• Other Study ID Numbers: ML45833

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No