Chronic Lymphocytic Leukemia (CLL)Early Phase 1NCT07428707
Immune Profiling of CLL/SLL Treated With First-Line Pirtobrutinib
A Early Phase 1 study testing Pirtobrutinib in people with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
- What is being tested?
- Pirtobrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Mar 2026to 1 Mar 2030
- Phase
- Early Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- OR
- 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.
- The patient has adequate organ function for all of the following criteria, as defined below:
- System: Hepatic
- Laboratory Value: ALT or AST: <= 3 x the ULN or <= 5 x ULN with documented liver involvement
- Laboratory Value: Total bilirubin: <= 1.5 x ULN or <= 3 x ULN with documented liver involvement and/or Gilbert s Disease
- System: Renal
- --Laboratory Value: Serum creatinine: Calculated creatinine clearance >= 30 ml/min according to Cockcroft/Gault Formula: [(140-age) x body weight (kg) x 0.85 (if female)]/ [serum creatinine (mg/dL) x 72]
- System: Hematologic
- Laboratory Value: Hemoglobin: >= 8 g/dL (>= 80 g/L)
- Laboratory Value: ANC: >= 0.75 x 10^9/L
- Laboratory Value: Platelets: >= 50 x 10^9/L
- Notes:
- Hgb and platelets: independent of transfusions within 7 days of Screening assessment.
- ANC: independent of growth factor support within 7 days of Screening assessment.
- Criteria must be met on C1D1 without transfusion/G-CSF within 7 days of assessment.
- Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST =aspartate aminotransferase; ULN = upper limit of normal.
- Adequate coagulations, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or international normalized ratio (INR) not greater than 1.5 X ULN.
- Willingness of WOCBP and their partners to observe highly effective birth control methods for the duration of treatment and for 1 month following the last dose of study treatment.
- Ability to take oral medication and be willing to adhere to the study drug regimen
- Agreement to adhere to Lifestyle Considerations throughout study duration
- Able to understand and willing to sign a written informed consent document.
Who cannot join
- 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:
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- 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
- Active, clinically significant cardiovascular disease including:
- Unstable angina or acute coronary syndrome within the past 2 months prior to screening
- Documentation of LVEF by any method of <= 40% in the 12 months prior to screening
- Uncontrolled or symptomatic arrhythmias
- Class 3 or 4 congestive heart failure as defined by New York Heart Association Functional Classification
- Myocardial infarction, unstable angina or acute coronary syndrome within 3 months of screening.
- Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec. QTcF is calculated using Fridericia s Formula (QTcF): QTcF=QT/(RR^0.33)
- Correction of suspected drug-induced QTcF prolongation can be attempted at the investigator s discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation.
- Correction for underlying bundle branch block (BBB) allowed.
- Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
- Known allergy/sensitivity to pirtobrutinib or any of the excipients (hydroxypropyl methylcellulose acetate succinate, microcrystalline cellulose, mannitol, sodium starch glycolate, and magnesium stearate.).
- History of bleeding diathesis (e.g. von Willebrand disease or hemophlia)
- Has received a live vaccine or live-attenuated vaccine within 28 days before the first dose of pirtobrutinib. Administration of killed vaccines are allowed.
- Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist are excluded. Direct oral anticoagulants (DOACs) are allowed.
- Diagnosis of primary immunodeficiency or is receiving chronic systemic steroid therapy (in dosing >20 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
- Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid)
- Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) for which new therapy was introduced or existing therapy was escalated within the 4 weeks prior to study enrollment to maintain adequate blood counts.
- Active second malignancy unless in remission and with life expectancy >2 years.
- Note: Participants are eligible if they have prostate cancer under active surveillance or observation.
- Has not adequately recovered after 4 weeks from major surgery or has ongoing surgical complications.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
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.
Read more
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....
Read the detailed description
Study Description: This is a pilot study of pirtobrutinib for previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL). Subjects will be treated with pirtobrutinib 200 mg by mouth once daily until disease progression or toxicity. Immune profiling of lymph node (LN) and peripheral blood (PB) will be performed at baseline and on pirtobrutinib. Circulating tumor cells will be analyzed at baseline and on pirtobrutinib. Efficacy and safety will be evaluated.
Objectives:
Primary Objective:
-Evaluate the immune cell composition of LN at baseline and on pirtobrutinib in patients with previously untreated CLL.
Secondary Objectives:
-Evaluate the immune cell composition of PB at baseline and on pirtobrutinib in patients with previously untreated CLL.
Exploratory Objectives:
- Characterize the transcriptome, immunophenotype, and specificity of immune cells at single-cell resolution at baseline and on pirtobrutinib
- Evaluate the immunophenotype of circulating immune cells at baseline and on pirtobrutinib
- Evaluate the cytotoxic and activation potential of T cells at baseline and on pirtobrutinib
- Characterize the transcriptome of circulating tumor cells at baseline and on pirtobrutinib
- Evaluate the efficacy of pirtobrutinib in previously untreated CLL
- Identify preliminary biomarkers of efficacy
- Evaluate the safety of pirtobrutinib in previously untreated CLL
Endpoints:
Primary Endpoint:
-Immune cell composition estimated by deconvolution of bulk RNA sequencing (RNA-seq) of LN at baseline and on C1D7
Secondary Endpoints:
-Immune cell composition estimated by deconvolution of bulk RNA-seq of PB mononuclear cells (PBMCs) at baseline and on C1D7 and C7D1
Exploratory Endpoints:
- Single-cell analysis of immune cells from LN and PB at baseline and on C1D7
- Expression of T-cell differentiation and activation markers by flow cytometric analysis of PBMCs at baseline, on C1D7, and on C7D1
- Anti-CLL cytotoxicity and activation of autologous T cells obtained at baseline and on C7D1 in response to T-cell engaging bispecific antibodies (bsAb)
- Bulk RNA-seq of CD19+ PBMCs at baseline, on C1D7, and on C7D1
- Overall response rate (ORR), progression-free survival (PFS), and minimal residual disease (MRD) status
- Association between biological parameters and clinical outcomes
- Incidence and severity of treatment-emergent adverse events (TEAEs)
- Being tested
- Pirtobrutinib
- Keywords
- Pirtobrutinib, Chronic Lymphocytic Leukemia (CLL), Immune profiling
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PirtobrutinibDrug
Pirtobrutinib will be administered orally at a dose of 200 mg once daily in 28-day cycles
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Pirtobrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline, Cycle 1 Day 7
Secondary outcomes (1)
Immune cell composition of peripheral blood at baseline and on pirtobrutinib
Immune cell composition estimated by deconvolution of bulk RNA-seq of peripheral blood mononuclear cells (PBMCs) at baseline and on C1D7 and C7D1
Measured: Baseline, Cycle 1 Day 7 and Cycle 7 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2026
- Study start11 Mar 2026
- Primary completion1 Feb 2030 (estimated)
- Study completion1 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic Leukemia (CLL)Studies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Laura S Samples, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07428707
- Sponsor's protocol ID
- 10002200
- Other IDs
- 002200-H
- Status last verified
- 20 Oct 2026
- First submitted
- 21 Feb 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided