Pirtobrutinib and Venetoclax With MRD Detection for Previously Untreated Chronic Lymphocytic Leukemia

Running, not enrolling · Phase 2

Conditions studied: Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

In brief

This phase II trial studies how well pirtobrutinib and venetoclax work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. This study also seeks to adopt a blood test which shows a small number of cancer cells in the body after cancer treatment called minimal residual disease as a guide to determine length of treatment. Drugs used in chemotherapy, such as pirtobrutinib and venetoclax, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Identifying minimal residual disease results after combination chemotherapy may help guide future treatment decisions for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Key facts

Study ID

NCT05677919

Run by

Mayo Clinic

People needed

72

Starts

2023-01-31

Expected to finish

2030-09-03

Last updated by the study team

2026-02-12

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• PRE-REGISTRATION - INCLUSION CRITERIA
• Age >= 18 years.
• Confirmed diagnosis of CLL according to the International Workshop on (iw)CLL 2018 criteria or biopsy proven small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria.
• NOTE: The diagnosis of CLL requires the presence of > 5 × 10\^9/L B lymphocytes in the peripheral blood. Typically, CLL cells express CD19, CD5, and CD23, with variable expression of CD20 (typically dim), and show kappa or lambda light chain restriction.
• NOTE: A diagnosis of mantle cell lymphoma must be excluded by demonstrating a negative cyclin D1 expression and/or a negative t(11;14) translocation.
• No prior CLL/SLL-directed therapy such as chemotherapy, immunotherapy, targeted therapy with small molecule inhibitors, radiation therapy, or cellular therapy.
• NOTE: Nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments or supplemental vitamins) will not be considered prior CLL/SLL-directed therapy.
• NOTE: Prior corticosteroid therapy for an indication other than CLL/SLL will not be considered prior CLL/SLL-directed therapy.
• NOTE: A short course of corticosteroid (e.g., =< 1 week of intravenous or =< 2 weeks of oral corticosteroid) given for acute SLL-related symptoms or impending severe organ dysfunction is allowed.
• Provide written informed consent.
• REGISTRATION - INCLUSION CRITERIA
• Patients with SLL must have a measurable B-cell clone (of CLL immunophenotype) in either peripheral blood or bone marrow (e.g., by flow cytometry) at baseline.
• Meeting at least one of the following indications for treatment:
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (Hb < 11 g/dL) and/or thrombocytopenia (platelet counts < 100 × 10\^9/L).
• Massive (i.e., >= 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
• Massive nodes (i.e., >= 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
• Progressive lymphocytosis with an increase of >= 50% over a 2-month period, or lymphocyte doubling time (LDT) < 6 months. LDT can be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months; patients with initial blood lymphocyte counts < 30 × 10\^9/L may require a longer observation period to determine the LDT. Factors contributing to lymphocytosis other than CLL (e.g., infections, steroid administration) should be excluded.
• Autoimmune complications including anemia or thrombocytopenia poorly responsive to corticosteroids.
• Symptomatic or functional extranodal involvement (e.g., skin, kidney, lung, spine).
• Disease-related symptoms as defined by any of the following:
• Unintentional weight loss >= 10% within the previous 6 months.
• Significant fatigue (i.e., cannot work or unable to perform usual activities).
• Fevers >= 100.4°F or 38.0°C for 2 or more weeks without evidence of infection.
• Night sweats for >= 1 month without evidence of infection.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2

You may not qualify if…

• REGISTRATION - EXCLUSION CRITERIA
• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant persons.
• Nursing persons (lactating persons are eligible provided that they agree not to breast feed while receiving treatment on the study or within 6 months of the last dose of study treatment).
• Male or females of reproductive potential who are unwilling to employ adequate contraception during treatment and for 6 months after pirtobrutinib.
• Evidence of Richter transformation.
• Central nervous system (CNS) involvement of CLL/SLL (e.g., any parenchymal, leptomeningeal, cerebrospinal fluid [CSF], cranial or spinal nerve root involvement).
• Active uncontrolled autoimmune complications (e.g., active autoimmune hemolytic anemia or clinically significant immune thrombocytopenia).
• Receiving any other investigational agent which would be considered as a treatment for the CLL/SLL (with the exception of corticosteroid).
• Any of the following medication requirement or recent use:
• Requirement of a strong cytochrome P450 (CYP) 3A inhibitor or inducer during the study.
• Use of a strong or moderate CYP3A inhibitor or inducer =< 7 days prior to registration.
• Requirement of a strong P-glycoprotein 1 (PgP) inhibitor during the study.
• Anticoagulation with a vitamin K antagonist =< 7 days prior to registration or anticipated use during the study.
• Vaccination with live vaccine =< 28 days prior to registration.
• NOTE: Because of their effect on CYP3A4, use of any of the following =< 3 days of study therapy start or planned use during study participation is prohibited:
• Grapefruit or grapefruit products.
• Seville oranges or products from Seville oranges.
• Star fruit.
• Malabsorption syndrome or other condition that precludes enteral route of administration.
• History of a bleeding diathesis (e.g., hemophilia, von Willebrand disease, etc.).
• Patients who have tested positive for Human Immunodeficiency Virus (HIV) are excluded due to potential drug-drug interactions between anti-retroviral medications and pirtobrutinib and risk of opportunistic infections with both HIV and irreversible BTK inhibitors. For patients with unknown HIV status, HIV testing will be performed at Screening and result should be negative for enrollment.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection.

Where it is running

• Mayo Clinic in Rochester — Rochester, Minnesota, United States

Full record on ClinicalTrials.gov

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