Phase II Study of Pirtobrutinib and Rituximab in Untreated Low and Intermediate Risk Mantle Cell Lymphoma Patients

Inclusion Criteria

• Adults aged 18 years or older.
• Diagnosed with mantle cell lymphoma (MCL) confirmed by pathology, with CD20 positivity. Certain cases with cyclin D1 negative MCL are allowed after confirmation.
• Newly diagnosed MCL with no prior treatment.
  • Low risk: Ki-67% 30% or less, no high-risk features, largest tumor size 3 cm or less.
  • Medium risk: Ki-67% 50% or less, largest tumor size 5 cm or less, no high-risk features.
• Participants with well-controlled cardiovascular conditions are allowed, including those on certain medications, with prior heart procedures, or with specific heart test results.
• Must understand and sign an informed consent form.
• Must have at least one site of disease that can be measured by scans, but certain isolated disease sites are allowed.
• ECOG performance status of 2 or less, indicating the ability to carry out light work.
• Blood clotting times within specified limits, with exceptions for certain conditions.
• Adequate bone marrow and organ function as determined by specific blood tests.
• Life expectancy of more than 12 weeks related to lymphoma.
• Female participants must be surgically sterile, postmenopausal, or have a negative pregnancy test before starting treatment.
• Participants must agree to use effective contraception during and after treatment, with specific methods recommended.

Exclusion Criteria

• Central nervous system involvement with MCL or certain brain conditions.
• High-risk MCL with specific features like certain cell types, large tumors, or genetic mutations.
• Recent major surgery.
• History of bleeding disorders.
• Active CMV infection.
• Uncontrolled infections or other significant health conditions.
• Significant heart diseases or recent heart events.
• Digestive system conditions affecting medication absorption.
• Pregnancy or breastfeeding during the study.
• Use of certain medications that affect drug metabolism.
• Difficulty swallowing or absorbing oral medication.
• Recent stroke or brain bleeding.
• Recent vaccination with live vaccines.
• Allergies to study drugs.
• Previous severe reactions to similar treatments.
• Positive HIV test or active hepatitis B or C infection.
• Other uncontrolled health conditions that may pose a risk.
• Prolonged QT interval on heart tests.
• Recent or active second cancers, with some exceptions.
• Use of other cancer treatments or recent major surgery.
• Uncontrolled autoimmune blood disorders.
• Chronic steroid use above a certain dose.
• History of certain transplants or serious medical conditions.