Immune Profiling of CLL/SLL Treated With First-Line Pirtobrutinib

NCT07428707 | Recruiting Early Phase 1

• 2 other identifiers: 10002200002200-H
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are blood cancers that affect certain white blood cells. Advanced forms of these diseases are difficult to treat. Pirtobrutinib is a drug approved to treat CLL and SLL after 2 previous treatments. Researchers want to know how this drug affects the immune system in those who have not yet started other treatments for CLL or SLL. Objective: To test pirtobrutinib as a first-line treatment for CLL or SLL. Eligibility: People aged 18 years and older with untreated CLL or SLL. Design: Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and tests of their heart function. They will have a lymph node biopsy: A large needle will be inserted into a lymph node to collect a small piece of tissue. Pirtobrutinib is a tablet taken by mouth. Participants will take 2 to 4 tablets daily in 4-week cycles. Participants will have clinic visits once every 4 weeks for the first 3 months. Then they will be seen once every 3 months. Imaging scans, lymph node biopsy, and other tests will be repeated at various study visits. A bone marrow biopsy (collection of soft tissue from inside a bone) may be done if there is no evidence of disease after 1 year of treatment with the study drug. Participants may opt to have cancer and immune cells collected from their blood. The cells will be used for research. Participants will have a clinic visit 1 month after their last dose of the study drug. Then they will have follow-up visits or phone calls every 6 to 12 months....

Conditions

Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)

Keywords

Pirtobrutinib; Chronic Lymphocytic Leukemia (CLL); Immune profiling

Outcome Measures

Primary Outcomes (1)

• Immune cell composition of lymph nodes at baseline and on pirtobrutinib

  Immune cell composition estimated by deconvolution of bulk RNA sequencing (RNA-seq) of lymph node (LN) at baseline and on C1D7

  Baseline, Cycle 1 Day 7

Secondary Outcomes (1)

• Immune cell composition of peripheral blood at baseline and on pirtobrutinib

  Baseline, Cycle 1 Day 7 and Cycle 7 Day 1

Study Arms (1)

Pirtobrutinib

EXPERIMENTAL

Pirtobrutinib will be administered orally at a dose of 200 mg once daily in 28-day cycles, and participants will continue treatment until disease progression, unacceptable toxicity, or meeting other discontinuation criteria

Drug: Pirtobrutinib

Interventions

Pirtobrutinib DRUG

Pirtobrutinib will be administered orally at a dose of 200 mg once daily in 28-day cycles

Pirtobrutinib

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Stated willingness to comply with all study procedures
• Age \>=18 years
• Confirmed diagnosis of CLL or SLL according to International Workshop on CLL (iwCLL) guidelines
• Coexpression of CD5, CD19, CD20, and CD23 expression and light-chain restriction; CD23 dim or negative expression is acceptable as long as other parameters are consistent with a diagnosis of CLL.
• CLL: clonal B-lymphocytosis \>=5,000 cells/mL
• SLL: lymphadenopathy with the tissue morphology of CLL but that are not leukemic, \<5,000 cells/mL
• Active disease requiring treatment according to iwCLL guidelines
• Measurable disease characterized by \>=1 of the following:
• Lymphadenopathy: \>=1 lymph node measuring \>=1.5 cm in the greatest diameter
• Splenomegaly: spleen measuring \>13 cm in craniocaudal length
• Lymphocytosis: \>=5,000 B cells/microL
• Bone marrow infiltration: CLL comprising \>= 30% of all cells
• Previously untreated CLL with \>=1 LN amenable to core-needle biopsy
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

You may not qualify if:

• Diagnosis of Richter Transformation
• Documented CNS involvement
• Pregnancy or plan to become pregnant during the study or within 1 month of the last dose of study treatment. WOCBP must have a negative serum pregnancy test.
• Lactation or plan to breastfeed during the study or within 1 week of the last dose of study treatment.
• Known active cytomegalovirus (CMV) infections. Unknown or negative status are eligible.
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
• Patients with positive hepatitis B surface antigen (HBsAg) are excluded.
• Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require a negative hepatitis B polymerase chain reaction (PCR) evaluation before randomization.
• Patients who are HBV DNA PCR positive will be excluded.
• Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before randomization. Patients who are hepatitis C RNA positive will be excluded.
• Patients who have tested positive for Human Immunodeficiency Virus (HIV) and have a detectable viral load and/or a CD4 count \<350 are excluded due to risk of opportunistic infections with both HIV and BTK inhibitors. Eligible patients with HIV must be stable on antiretroviral therapy \>=4 weeks prior to study entry. For patients with unknown HIV status, HIV testing will be performed at Screening and result must be negative for enrollment.
• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drug. (e.g., gastric bypass surgery, gastrectomy).
• Evidence of other clinically significant uncontrolled condition(s) including but not limited to, uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator and medical monitor may pose a risk for patient participation. Screening for chronic conditions is not required.
• Stroke or intracranial hemorrhage within 6 months of screening
• Hypertensive urgency or emergency

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

pirtobrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Laura S Samples, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NIH Clinical Center Office of Patient Recruitment (OPR)

CONTACT

(800) 411-1222; ccopr@nih.gov

Laura S Samples, M.D.

CONTACT

(301) 827-1203; laura.samples@nih.gov

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2026
• First Posted: February 24, 2026
• Study Start: March 11, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: July 21, 2026

Record last verified: 2026-07-17

Locations

US (1)