NCT05677919

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

MC210806 Phase 2 Study of MRD Guided, FIxed DuRation TherApy for Previously Untreated Chronic Lymphocytic LeukEmia With Pirtobrutinib and Venetoclax (MIRACLE)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVE: I. To assess the rate of undetectable minimal residual disease (MRD) (uMRD, by ClonoSEQ) in both peripheral blood and bone marrow after 15 cycles of treatment. SECONDARY OBJECTIVES: I. To assess best peripheral blood uMRD rate and best bone marrow uMRD rate by ClonoSEQ. II. To assess progression-free survival (PFS). III. To assess overall response rate (ORR) and complete response (CR) rate. IV. To assess duration of response (DOR), time to next treatment (TTNT), and overall survival (OS). V. To assess toxicities associated with pirtobrutinib and venetoclax. CORRELATIVE RESEARCH OBJECTIVE: I. To analyze the dynamics of MRD (by ClonoSEQ) and its association with response to treatment and clinical outcomes. OUTLINE: Patients receive pirtobrutinib orally (PO) daily (QD) on days 1-28 of each cycle and venetoclax PO QD starting in cycle 4 on days 1-28 of each cycle. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/CT scans during screening and on study. Patients also undergo bone marrow aspiration and biopsy and collection of blood samples throughout the study and collection of stool and saliva on study. Patients may undergo tissue biopsy, echocardiography (ECHO), or multigated acquisition (MUGA) scan during screening. After completion of study treatment, patients follow up at 30 days and every 6 months for up to 3 years for clinical follow-up and then every 6 months for up to 5 years after registration for survival follow-up.

Conditions

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood, tissue, stool, and saliva samples
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
PROCEDURE	Computed Tomography	Undergo CT scan
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI scan
DRUG	Pirtobrutinib	Given PO
PROCEDURE	Positron Emission Tomography	Undergo PET scan
DRUG	Venetoclax	Given PO
PROCEDURE	Echocardiography	Undergo ECHO
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
PROCEDURE	Biopsy	Undergo tissue biopsy

Timeline

• Start date: 2023-01-31
• Primary completion: 2026-11-11
• Completion: 2030-09-03
• First posted: 2023-01-10
• Last updated: 2026-02-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study