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

Official title

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

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• 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. [Time frame: 24 months]

Secondary outcome measures (6)

• Objective Response Rate (ORR) [Time frame: up to 24 months]
• complete response rate (CRR) [Time frame: Up to 24 months]
• Duration of Response (DoR) [Time frame: Up to 48 months]
• Duration of Complete Response (DoCR) [Time frame: Up to 48 months]
• Progression-Free Survival (PFS) [Time frame: Up to 48 months]
• Overall Survival (OS) [Time frame: Up to 48 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University Third Hospital — Beijing

Identifiers

NCT: NCT07460362 · ML45833

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗