Glofitamab plus lenalidomide for high‑risk relapsed or refractory mantle cell lymphoma after 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

This trial tests whether giving glofitamab with oral lenalidomide helps adults with high‑risk mantle cell lymphoma that has returned or not responded after prior treatments including a BTK inhibitor.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Peking University Third Hospital (Academic / other)
• Drugs / interventions: ibrutinib, zanubrutinib, obrutinib, acalabrutinib, glofitamab, Obinutuzumab
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07460362 on ClinicalTrials.gov

What this trial studies

This is a single‑arm, open‑label phase 2 trial using a Simon two‑stage design to test the combination of intravenous glofitamab and oral lenalidomide in adults with high‑risk relapsed or refractory mantle cell lymphoma who have previously received a BTK inhibitor. Patients receive two 1000 mg doses of obinutuzumab before starting glofitamab, with glofitamab given IV and lenalidomide self‑administered orally during induction. The primary endpoint is best overall response rate at the end of induction assessed by PET/CT using Lugano criteria, and secondary aims include complete response rate, safety, and exploratory biomarker studies such as ctDNA and total metabolic tumor volume. Enrollment is restricted to adults 18–80 with ECOG ≤2 and at least one high‑risk feature, and the two‑stage design allows early stopping for lack of efficacy.

Who should consider this trial

Good fit: Adults aged 18–80 with relapsed or refractory mantle cell lymphoma, prior exposure to a BTK inhibitor, ECOG ≤2, and at least one high‑risk feature (e.g., blastoid variant, TP53 abnormality, bulky disease, or early relapse) are ideal candidates.

Not a fit: Patients without prior BTK inhibitor exposure, those with low‑risk or newly diagnosed MCL, or people with significant comorbidities or organ dysfunction that make them ineligible are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could increase response rates and provide a new treatment option for high‑risk MCL patients who have progressed after BTK inhibitors.

How similar studies have performed: Glofitamab and other CD20×CD3 bispecific antibodies have shown promising activity in relapsed B‑cell lymphomas in earlier studies, but the specific combination with lenalidomide in high‑risk MCL is less well established.

Eligibility criteria

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.

Where this trial is running

Beijing, Beijing Municipality

• Peking University Third Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Hongmei Jing

Conditions MCL; Relapsed or Refractory Mantle Cell Lymphoma; Relapsed or Refractory MCL, previously treated with a BTK Inhibitor