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Chronic Lymphocytic LeukemiaPhase 1/2NCT05317936

Pirtobrutinib (LOXO-305) Consolidation for MRD Eradication in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) Treated With Venetoclax

A Phase 1/2 study testing Pirtobrutinib and Venetoclax in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

To learn if the combination of LOXO-305 (pirtobrutinib) and venetoclax can help to control previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pirtobrutinib and Venetoclax
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
16 Nov 2022to 6 Oct 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of CLL per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria
  • Received venetoclax for at least 12 cycles, with MRD > 0.01% detectable in peripheral blood, by Adaptive Biotechnologies NGS assay, within the month prior to study enrollment
  • Age 18 years or older
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Serum bilirubin =< 1.5 x upper limit of normal (ULN) or =< 3 x ULN for patients with Gilbert's disease
  • Serum creatinine clearance of >= 30 ml/min (calculated or measured)
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  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 x ULN, unless clearly due to documented disease involvement, in which case ALT and AST =< 5.0 x ULN
  • Platelet count of >= 50,000/ul, with no platelet transfusion in prior 2 weeks
  • Absolute neutrophil count (ANC) >= 1000/ul in the absence of growth factor support
  • Hemoglobin >= 8 mg/dL
  • Activated partial thromboplastin time (aPTT) or partial thromboplastin time and prothrombin time (PT) or international normalized ratio (INR) not greater than 1.5 x ULN
  • Ability to provide informed consent and adhere to the required follow-up
  • Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 7 days prior to the first dose of study drugs and must agree to use use both a highly effective method of birth control (e.g., implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence, or sterilized partner) and a barrier method (e.g., condoms, vaginal ring, sponge, etc) during the period of therapy and for 6 months after the last dose of study drug. Women of non-childbearing potential are those who are postmenopausal (defined as absence of menses for >= 1 year) or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use effective contraception, defined above, during the study and for 30 days following the last dose of study drug

Who cannot join

  • Known or suspected Richter's transformation to diffuse large B cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin lymphoma at any time preceding enrollment
  • Known or suspected history of central nervous system (CNS) involvement by CLL
  • History of grade >= 3 arrhythmia on prior covalent Bruton's tyrosine kinase (BTK) inhibitor
  • Patients who experienced a major bleeding event on a prior BTK inhibitor
  • NOTE: Major bleeding is defined as bleeding having one or more of the following features: life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2 g/dL; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome)
  • Active second malignancy. Patients with a treated second malignancy and with likelihood of requiring systemic therapy within the next 2 years of < 10%, as determined by an expert in the field, will be eligible. Examples include:
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  • Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
  • Adequately treated cervical carcinoma in situ without current evidence of disease
  • Localized (e.g., lymph node negative) breast cancer treated with curative intent with no evidence of active disease present for more than 3 years and receiving adjuvant hormonal therapy
  • Localized prostate cancer undergoing active surveillance
  • History of treated and cured Hodgkin's disease or non-Hodgkin lymphoma (NHL) < 5 years from diagnosis
  • Major surgery within 4 weeks of planned start of study therapy
  • A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disorder, that, in the opinion of the Investigator, would adversely affect the patient's participation in this study or interpretation of study outcomes
  • History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor (CAR)-T therapy within the past 60 days or presence of any of the following, regardless of prior SCT and/or CAR-T therapy timing:
  • Active graft versus host disease (GVHD)
  • Need for anti-cytokine therapy for toxicity from CAR-T therapy
  • Residual symptoms of neurotoxicity > grade 1 from CAR-T therapy
  • Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
  • Significant cardiovascular disease, defined as any of the following:
  • Unstable angina or acute coronary syndrome within the past 2 months
  • History of myocardial infarction within 6 months prior to planned start of study treatment
  • Documented left ventricular ejection fraction (LVEF) by any method of =< 45% in the 12 months prior to planned start of study treatment
  • >= grade 3 New York Heart Association (NYHA) functional classification system of heart failure
  • Uncontrolled or symptomatic arrhythmias
  • Prolongation of the QT interval corrected (QTc) for heart rate using Fredericia's Formula (QTcF) > 470 msec on an electrocardiogram (EKG) during screening
  • QTcF is calculated using Fredericia's Formula
  • Correction of suspected drug-induced QTcF prolongation or prolongation due to electrolyte abnormalities 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 or electrolyte supplementation
  • Correction of QTc for underlying bundle branch block (BBB) permissible
  • Hepatitis B or hepatitis C testing indicating active/ongoing infection based on screening laboratory tests as defined as:
  • Hepatitis B virus (HBV): Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation. Patients who are hepatitis B 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
  • Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal) or other clinically significant active disease process which in the opinion of the Principal Investigator may pose a risk for patient participation. Screening for chronic conditions is not required
  • Known human immunodeficiency virus (HIV) infection, regardless of CD4 count. Patients with unknown or negative status are eligible
  • Known active cytomegalovirus (CMV) infection. Patients with unknown or negative status are eligible
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the oral administered study treatments
  • Investigational agent or anti-cancer therapy other than venetoclax, with the exception of hormonal therapy for breast or prostate cancer. Other agents must be discontinued for at least 4 weeks for monoclonal antibody therapy or 5 half lives for other agents
  • Use of > 20 mg prednisone QD or equivalent dose of steroid per day at the time of cycle 1 day 1 (C1D1). Patients may not be on prednisone of any dose intended for anti-neoplastic use
  • Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
  • Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inducers and/or strong P-glycoprotein (P-gp) inhibitors. Because of their effect on CYP3A4, use of any of the following within 3 days of study treatment start or planned use during study participation is prohibited:
  • Grapefruit or products from grapefruit
  • Seville oranges or products from Seville oranges
  • Star fruit or products from star fruit
  • Vaccination with a live vaccine within 28 days prior to study start
  • Previous treatment with another non-covalent BTK inhibitor, such as nemtabrutinib
  • Pregnancy, lactation or plan to breastfeed during the study or within 30 days of the last dose of study treatment
  • Patients with known hypersensitivity to any component or excipient of LOXO-305 and venetoclax
  • Any unresolved toxicity from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) grade 2 at the time of starting study treatment, except for alopecia

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

To learn if the combination of LOXO-305 (pirtobrutinib) and venetoclax can help to control previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Read the detailed description

Primary Objective:

  1. To estimate the therapeutic efficacy of pirtobrutinib consolidation in patients who have detectable CLL in peripheral blood after receiving venetoclax for at least 12 cycles. The primary endpoint will be the rate of undetectable MRD (U-MRD4) in the peripheral blood, assessed by NGS at a threshold of 0.01% sensitivity, after 24 cycles of combination therapy.

SECONDARY OBJECTIVES:

  1. Determine the complete remission (CR)/complete remission with incomplete marrow recovery (CRi) rate after 6, 12 18 and 24 cycles of combination therapy, in patients who were not in CR/CRi at study initiation and estimate the time to best response with this combination.

II. Determine the cumulative rate of blood and bone marrow minimal residual disease undetectable minimal residual disease (MRD) by next generation sequencing (NGS) at thresholds of 0.01% sensitivity (MRD4), 0.001% sensitivity (MRD5) and 0.0001% sensitivity (MRD6).

III. Achievement of undetectable MRD at a sensitivity of 0.0001% (MRD6) in the bone marrow in patients who achieve undetectable (U)-MRD6 in peripheral blood.

IV. Determine the safety of combined pirtobrutinib and venetoclax. V. Determine the progression-free and overall survival.

OUTLINE:

Patients receive pirtobrutinib orally (PO) once daily (QD) and venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After 24 cycles of combination therapy, patients who achieve U-MRD4 discontinue therapy. Patients who do not achieve U-MRD4 receive pirtobrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks, and then every 24 weeks (6 months) for up to 5 years.

Being tested
Pirtobrutinib, Venetoclax
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

    Also called LOXO-305

    Given by PO

  • VenetoclaxDrug

    Also called ABT-199, GDC-0199

    GIven by PO

Study groups in NCT05317936
Study groupRoleWhat they receive
Pirtobrutinib+venetoclaxExperimentalPirtobrutinib by mouth at the same time each day Venetoclax by mouth at the same time each day.
Receives: Drug: Pirtobrutinib; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of undetectable (U) minimal residual disease (MRD) in the peripheral blood

    Assessed by next generation sequencing (NGS) at a threshold of 0.01% sensitivity. The rate of U-MRD will be reported separately for each cohort, along with the corresponding exact 95% confidence interval.

    Measured: Up to completion of cycle 24 (each cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2022
  2. Study start16 Nov 2022
  3. Primary completion6 Oct 2025
  4. Study completion6 Oct 2025

Why it stopped: \<75% participation

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05317936
Sponsor's protocol ID
2021-0953
Other IDs
NCI-2022-02427
Status last verified
Dec 2025
First submitted
15 Mar 2022
Last updated
15 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pirtobrutinib and Venetoclax in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: \<75% participation). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of undetectable (U) minimal residual disease (MRD) in the peripheral blood (time frame: Up to completion of cycle 24 (each cycle is 28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05317936.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025.

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