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Chronic Lymphocytic LeukemiaPhase 2PIPOZANCT06812715

Clonal Dynamics of Chronic Lymphocytic Leukaemia Treated With Pirtobrutinib After Previous Treatment With Zanubrutinib

A Phase 2 study testing Pirtobrutinib in people with Chronic Lymphocytic Leukemia, run by Peter MacCallum Cancer Centre, Australia at 3 sites in Australia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a multicentre single-arm prospective phase II trial evaluating pirtobrutinib in the treatment of relapsed/refractory (R/R) Chronic Lymphocytic Leukaemia (CLL) patients who have previously received zanubrutinib, and to specifically evaluate Bruton Tyrosine Kinase (BTK) mutational status (clonal dynamics)… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
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
40 participants
Where
3 sitesAustralia
Study dates
5 May 2025to May 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Patient has provided written informed consent using the PIPOZA Patient Information and Consent Form (PICF)
  • Confirmed diagnosis of CLL according to iwCLL 2018 criteria, also including CLL with atypical immunophenotype
  • Prior systemic therapy, which must include zanubrutinib as the most recent prior line of therapy. Patients must have received at least one cycle (28 days) of zanubrutinib
  • Patients must have an indication for second- or subsequent-line treatment in the opinion of the investigator as defined by iwCLL 2018 criteria, including:
  • Where the original indication for treatment has not resolved with initial therapy and it is considered reasonable to initiate second-line treatment without waiting for formal disease progression to be manifest
  • Where the rate of disease progression is considered rapid, and initiation of subsequent therapy is considered acceptable before formal progression where there is substantial persisting disease burden
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  • Age 18 years of age or older at time of signing the PICF
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Must have adequate bone marrow function, as defined below:
  • Absolute neutrophil count > 0.75 × 109/L; if marrow is known to be infiltrated by CLL, granulocyte-colony stimulating factor (G-CSF) support may be used to achieve eligibility criteria
  • Platelets ≥ 30 × 109/L independent of transfusions within 7 days prior to screening assessment
  • Haemoglobin ≥ 70 g/L independent of transfusions within 7 days prior to screening assessment
  • Normal hepatic function defined as:
  • Total bilirubin ≤ 1.5× upper limit of normal (ULN) or ≤ 3.0 x ULN with documented liver involvement and/or Gilbert's Disease
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 × ULN or ≤ 5.0 × ULN with documented liver involvement
  • Adequate renal function defined as creatinine clearance of > 30 mL/minute calculated by Cockroft-Gault formula or using biochemical or nuclear medicine techniques
  • Ability to swallow tablets
  • Patients must have had a zanubrutinib washout period of at least 24 hours prior to the planned start date of pirtobrutinib on Day 1 Cycle 1
  • Prior treatment-related adverse events must have recovered to Grade ≤ 1 or pretreatment baseline with the exception of alopecia and Grade 2 peripheral neuropathy
  • Women of childbearing potential defined as not postmenopausal for at least 2 years or surgically sterile must have a negative serum pregnancy test documented within 14 days prior to planned started date of pirtobrutinib on Day 1 Cycle 1
  • Men with partners of childbearing potential or women of childbearing potential must agree to use a highly effective contraceptive method of birth control during study treatment and for at least 6 months following the last dose of study drug. Sperm donation is prohibited during the duration of participation in this study and for 6 months after the last dose of study drug. Acceptable methods of birth control are:
  • Combined estrogen and progestin containing hormonal contraception associated with inhibition of ovulation given orally, intravaginally, or transdermally
  • Progestin-only hormonal contraception associated with inhibition of ovulation given orally, by injection, or by implant
  • Intrauterine device Intrauterine hormone-releasing system
  • Bilateral tubal occlusion
  • Vasectomised partner
  • Sexual abstinence: Considered a highly effective method only if defined as refraining from heterosexual intercourse during an entire period of risk associated with the study treatment. The reliability of sexual abstinence needs will be evaluated in relation to the duration of the study and to the usual lifestyle of the patient
  • The patient understands the purpose of the trial and procedures required for the trial which includes compliance with the protocol requirements and restrictions listed in the PICF and in this protocol

Who cannot join

  • Known or suspected Richter's Transformation to diffuse large B-cell lymphoma, prolymphocytic leukaemia, or Hodgkin lymphoma at any time prior to registration
  • Known or suspected history of central nervous system involvement
  • History of allogeneic or autologous stem cell transplant or chimeric antigen receptor T-cell (CAR-T) therapy within the past 60 days and/or with any of the following:
  • Active graft versus host disease
  • Cytopenias from incomplete blood cell count recovery post-transplant or CAR-T therapy
  • Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity Grade > 1 from CAR-T therapy
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  • Ongoing immunosuppressive therapy
  • Positive serology for human immunodeficiency virus (HIV) test in Screening 5. Concurrent anticancer therapy
  • 6. Use of ≥ 20 mg prednisone QD or equivalent dose of steroid per day within 7 days prior to the planned pirtobrutinib start date on Day 1 Cycle 1. Patients may not be on prednisone of any dose intended for antineoplastic use 7. Vaccination with a live vaccine within 28 days prior to registration 8. Prolongation of the corrected QT interval using the Fredericia formula (QTcF) > 470 msec (QTcF is calculated using Fridericia's Formula: QTcF = QT / [RR0.33])
  • 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
  • Manual correction for underlying bundle branch block is allowed Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker 9. Female patient who is pregnant or plans to become pregnant within 1 month after the last dose of study treatment 10. Female patient who is lactating or plans to breastfeed during the study or within 1 week after the last dose of study drug 11. Active second malignancy 12. Clinically significant active malabsorption syndrome including surgical resection of small intestine or other condition likely to affect gastrointestinal (GI) absorption of the oral administered study drugs 13. Active hepatitis B or C infection defined as:
  • Hepatitis B virus (HBV): positive hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (anti-HBc). If anti-HBc positive with surface antigen negative, patient will need to have a negative result for hepatitis B DNA before start of study therapy. Patients who are anti-HBc positive and hepatitis B polymerase chain reaction 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 start of study therapy. Patients who are hepatitis C RNA positive will be excluded 14. Known active cytomegalovirus infection Note: Patients with an unknown or negative status are eligible 15. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, parasitic, or fungal) or other clinically significant active disease process which, in the opinion of the investigator, may pose a risk for patient participation. Screening for chronic conditions is not required 16. Active uncontrolled auto-immune cytopenia (e.g., autoimmune haemolytic anaemia, idiopathic thrombocytopenic purpura) where new therapy is introduced, or concomitant medication escalated within the 4 weeks prior to registration is required to maintain adequate blood counts. Stable controlled auto-immune cytopenias are allowed as long as required blood count criteria are met 17. Prior treatment with pirtobrutinib 18. Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist 19. Known hypersensitivity to any component or excipient of pirtobrutinib 20. Significant cardiovascular disease defined as:
  • Unstable angina or acute coronary syndrome within the past 2 months prior to registration
  • History of myocardial infarction within 3 months prior to registration
  • Documented left ventricular ejection fraction by any method of ≤ 40% in the 12 months prior to registration
  • ≥ Grade 3 New York Heart Association functional classification system of heart failure
  • Uncontrolled or symptomatic arrhythmias 21. History of uncontrolled or symptomatic arrhythmias including Grade ≥ 3 arrhythmia on a prior BTKi 22. History of major bleeding on a prior BTKi NOTE: Major bleeding is defined as bleeding having 1 or more of the following features: potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the Hb level of at least 20 g/L; or bleeding in a critical area or organ (e.g., retroperitoneal, intra-articular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome) 23. History of stroke or intracranial haemorrhage within 6 months prior to registration 24. Major surgery within 4 weeks prior to registration 25. History of bleeding diathesis 26. Current treatment with strong P-glycoprotein (P-gp) inhibitors

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Australia3 sites, 3 recruiting

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

    John F Seymour, +61385595000, john.seymour@petermac.org

    Recruiting

  • Alfred Hospital

    Melbourne, Victoria, 3004

    Constantine Tam, +61390765531, Constantine.tam@alfred.org.au

    Not yet recruiting

  • Monash Medical Centre

    Melbourne, Victoria, 3168

    Stephen Opat, +6139594 6666, Stephen.Opat@monash.edu

    Not yet recruiting

Other trials in Australia

About this study

This is a multicentre single-arm prospective phase II trial evaluating pirtobrutinib in the treatment of relapsed/refractory (R/R) Chronic Lymphocytic Leukaemia (CLL) patients who have previously received zanubrutinib, and to specifically evaluate Bruton Tyrosine Kinase (BTK) mutational status (clonal dynamics) before, during and after treatment with pirtobrutinib.

Read the detailed description

Following confirmation of eligibility and registration to the study, patients will receive treatment with pirtobrutinib until progressive disease (PD) according to International Workshop on Chronic Lymphocytic Leukaemia (iwCLL) 2018 criteria, unacceptable toxicity, or patient withdrawal. Following first progression, treatment may continue if in the opinion of the investigator the patient is deriving clinical benefit.

BTK mutational status and analysis of CLL clonal dynamics on peripheral blood will be performed prior to the first dose of treatment, Day 1 of each cycle thereafter while on study treatment, End of Treatment (EoT), and at time of PD.

Response will be assessed by the investigator based on physical examination, CT scan (or MRI), haematology results, and bone marrow examinations according to iwCLL 2018 response criteria.

Patients who discontinue treatment for any reason will have an EoT visit within 7 days after the last dose of treatment or decision to cease treatment. Additionally, they will have a Safety Follow-up visit 28 days + 7 days after the last dose of treatment or decision to discontinue treatment. Following these two visits, patients will move into the Follow-up Phase of the study where they will be assessed every 12 weeks ± 4 weeks. Patients with PD will be followed for survival and new anti-CLL therapy only. All patients will be followed up until the last registered patient has been on pirtobrutinib for 36 months without PD.

Being tested
Pirtobrutinib
Keywords
Pirtobrutinib, Bruton Tyrosine Kinase, BTK mutation, clonal dynamics, CLL, BTK inhibitor, Chronic Lymphocytic Leukaemia, Leukaemia
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, B-Cell, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PirtobrutinibDrug

    Pirtobrutinib is a first-in-class, oral noncovalent Bruton tyrosine kinase (BTK) inhibitor (BTKi) that was approved in January 2023 in the United States for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL) and later that same year CLL. It is currently being investigated across several global randomised phase III trials for frontline and R/R chronic lymphocytic leukaemia (CLL).

Study groups in NCT06812715
Study groupRoleWhat they receive
Treatment ArmExperimentalIn this single-arm study, patients will receive 200mg of pirtobrutinib once daily on Day 1-28 of each 28-day cycle.
Receives: Drug: Pirtobrutinib

What is being measured

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

  1. Cloncal dynamics of BTK mutations in CLL before, during and after treatment with pirtobrutinib

    Measured: Before the start of treatment till end of study, up until the last registered patient has been on pirtobrutinib for 36 months without progressive disease

Secondary outcomes (8)

  1. Overall response rate in CLL with pirtobrutinib after prior immediate zanubrutinib

    Measured: From the start of treatment till end of study, up until the last registered patient has been on pirtobrutinib for 36 months without progressive disease

  2. The efficacy as assessed by time to response (TTR)

    The time from the start of pirtobrutinib to the first objective response observed for patients who achieves a complete remission (CR), complete remission with an incomplete marrow recovery (CRi), nodular partial remission (nPR), partial remission (PR) or the initiation of subsequent anticancer therapy. TTR also includes partial remission with lymphocytosis (PR-L) as sensitivity analysis

    Measured: From the start of treatment till end of study, up until the last registered patient has been on pirtobrutinib for 36 months without progressive disease

  3. Efficacy as assessed by Duration of Response (DOR)

    The time from onset of a CR, CRi, nPR, PR to the earlier of the documentation of definitive progressive disease ([PD] per iwCLL 2018 criteria) or death from any cause, whichever occurred first. Duration of response and time to response will be evaluated for responders (CR, CRi, nPR, PR) only. DOR including PR-L as a response will be analysed with the same method as DOR

    Measured: From the start of treatment till end of study, up until the last registered patient has been on pirtobrutinib for 36 months without progressive disease

  4. Efficacy as assessed by Disease Control Rate (DCR)

    The percentage of patients who have achieve CR, CRi, nPR, PR, PR-L, or SD

    Measured: From the start of treatment till end of study, up until the last registered patient has been on pirtobrutinib for 36 months without progressive disease

  5. Efficacy as assessed by Time to next treatment (TTNT)

    The time from the date of first pirtobrutinib dose (Day 1 Cycle 1) to the date of the initiation of the next systemic anticancer therapy for CLL or death from any cause, whichever occurs first

    Measured: From the start of treatment till end of study, up until the last registered patient has been on pirtobrutinib for 36 months without progressive disease

  6. Efficacy as assessed by progression free survival

    The time from the date of first pirtobrutinib dose (Cycle 1 Day 1) until PD (per iwCLL 2018 criteria) or death from any cause, whichever occurs first

    Measured: From the start of treatment till end of study, up until the last registered patient has been on pirtobrutinib for 36 months without progressive disease

  7. Efficacy as assessed by overall survival

    The time from first pirtobrutinib dose (Day 1 Cycle 1) until death from any cause. If the patient is alive or lost to follow-up at the time of data analysis, OS data will be censored on the last date the patient is known to be alive

    Measured: From the start of treatment till end of study, up until the last registered patient has been on pirtobrutinib for 36 months without progressive disease

  8. Adverse Events (AEs) and Serious Adverse Events (SAEs) measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

    Safety profile, including SAEs, AEs, deaths, and clinical laboratory abnormalities

    Measured: From the start of treatment till end of study, up until the last registered patient has been on pirtobrutinib for 36 months without progressive disease

Timeline

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

  1. First posted6 Feb 2025
  2. Study start5 May 2025
  3. Primary completionMay 2029 (estimated)
  4. Study completionMay 2031 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06812715
Sponsor's protocol ID
23/028
Acronym
PIPOZA
Status last verified
Sep 2026
First submitted
2 Feb 2025
Last updated
3 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pirtobrutinib in people with Chronic Lymphocytic Leukemia, run by Peter MacCallum Cancer Centre, Australia at 3 sites in Australia.

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 28 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Australia. 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 phase mean?

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?

This study is still under way. Results are not available in the source record yet.

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

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cloncal dynamics of BTK mutations in CLL before, during and after treatment with pirtobrutinib (time frame: Before the start of treatment till end of study, up until the last registered patient has been on pirtobrutinib for 36 months without progressive disease). 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 NCT06812715.

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 3 Sep 2026.

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