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CLL (Chronic Lymphocytic Leukemia)Phase 2PACIFICNCT07624799

Fixed Duration Treatment With Combined Pirtobrutinib and Short Course Immuno-chemotherapy in Fit Patients With Previously Untreated Symptomatic Chronic Lymphocytic Leukemia (CLL).

A Phase 2 study testing Pirtobrutinib, Fludarabine and Cyclophosphamide in people with CLL (Chronic Lymphocytic Leukemia), run by French Innovative Leukemia Organisation.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
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Trial summary

The evidence base in support of fixed-duration, first-line approaches in medically fit patients with CLL is clearly strengthening, whether through combining targeted agents with immunochemotherapy or through chemotherapy-free combinations. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
CLL (Chronic Lymphocytic Leukemia)
What is being tested?
Pirtobrutinib, Fludarabine and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
82 participants
Where
No sites listed yet
Study dates
1 Sep 2026to 1 Sep 2033
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

  • Immunophenotypically confirmed CLL according to IWCLL 2018 guidelines
  • Binet stage C or Binet stage A and B with active disease could be considered for inclusion according to IWCLL 20108 for initiation of treatment.
  • Absence of Del(17p) and TP53 mutation in NGS (cut off 1%)
  • ECOG performance status 0-2
  • CIRS (Cumulative Illness Rating Scale) ≤ 6
  • Adequate coagulation: 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
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  • Calculated creatinine clearance ≥ 30 ml/min according to Cockcroft/Gault Formula: (140 - age) × body weight (kg) × 0.85 (if female) serum creatinine (mg/dL) × 72
  • Adequate liver function:
  • Aspartate aminotransferase (AST)/alanine aminotransferase or (ALT) ≤ 3 × the ULN or ≤ 5 × ULN with documented liver involvement,
  • Total bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN with documented liver involvement and/or Gilbert's Disease"
  • Adequate hematology values:
  • absolute neutrophil count ≥ 0.75 x 109/L,
  • platelet count ≥ 50 x 109/L (accordance to the coordinator if linked to the disease),
  • Hemoglobin ≥ 80g/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
  • Prior vaccination to the SARS-Cov-2 virus and SARS-CoV-2 PCR testing (if clinically indicated) and negative result before study treatment administration at each treatment cycle
  • The patient is able to take oral medications
  • Signed written informed consent
  • Willing or able to participate in all required study evaluations and procedures.
  • Ability to understand the purpose and risks of the study and to provide a signed and dated informed consent form and authorization to use protected health information (in accordance with national and local subject privacy regulations)

Who cannot join

  • Presence of Clonal hematopoiesis of indetermined potential or CHIP (To define patients with CHIP: Presence of a myeloid mutation (whatever the mutation) with a VAF >2% in the granular fraction
  • Binet stage A without active disease according to IWCLL 20108 criteria
  • Life expectancy < 6 months
  • Current or past history or presence of clinically relevant disorder affecting the central nervous system (CNS)
  • Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
  • Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
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  • Uncontrolled and/or active systemic infection (viral, bacterial or fungal): Known history of human immunodeficiency virus, serologic status reflecting active hepatitis B virus or hepatitis C virus infection, any uncontrolled active systemic infection along with subjects who are ongoing anti-infective treatment and subjects who have received vaccination with a live attenuated vaccine within 4 weeks before the first dose of study treatment
  • Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antibody (anti-HBs) negative will need to have a negative hepatitis B virus PCR result before enrollment. Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B virus PCR positive will be excluded.
  • Subjects who are hepatitis C virus antibody positive will need to have a negative hepatitis C virus PCR result before enrollment. Those who are hepatitis C virus PCR positive will be excluded
  • Known active cytomegalovirus (CMV) infection. Unknown or negative status are eligible.
  • Active and uncontrolled autoimmune cytopenia, including autoimmune hemolytic anemia (AIHA) (isolated positive DAT is not an exclusion criteria) and idiopathic thrombocytopenic purpura (ITP).
  • Concomitant disease requiring prolonged use of corticosteroids (> 1 month)
  • Patients treated by vitamin K antagonist or dual antiaggregant or anticoagulants (coumadin, warfarin)
  • History of bleeding diathesis (e.g. hemophilia or von Willebrand disease)
  • Prior solid organ transplantation
  • Concurrent severe diseases that exclude the administration of therapy :
  • Heart insufficiency NYHA grade III/IV, LEVF LVEF < 50% and or RF < 30%, myocardial infarction within the past 6 months prior to study
  • Significant cardiovascular disease such as symptomatic arrhythmias (including atrial fibrillation), congestive heart failure, unstable angina or acute coronary syndrome within the past 2 months prior to randomization or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional (Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study)
  • Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec. QTcF is calculated using Fridericia's Formula (QTcF): 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.
  • Correction for underlying bundle branch block (BBB) allowed
  • Severe chronic obstructive lung disease with hypoxemia
  • History of stroke or intra-cranial hemorrhage within the last 6 months
  • Severe diabetes mellitus
  • Uncontrolled hypertension
  • Impaired renal function with creatinine clearance < 30 ml/min according the formula of Cockroft and Gault
  • Patient who requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole (unless of separate dosing of pirtobrutinib capsules with antacids by at least 2 hours. Pirtobrutinib capsules should be taken 2 hours before an H2-receptor antagonist. Avoid co-administration of pirtobrutinib capsules with proton pump inhibitors).
  • Disease significantly affecting gastrointestinal function (malabsorption syndrome, stomach or small bowel resection)
  • Evidence for Richter syndrome
  • Treatment with any of the following within 7 days prior to the first dose of study drug: steroid therapy (see criteria 7 above) for anti-neoplastic intent.
  • A significant history of renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the investigator's opinion, would adversely affect the patient's participation in this study or interpretation of study outcomes.
  • Major surgery within 30 days prior to the first dose of study treatment.
  • History of prior other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of the following:
  • Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time prior to study.
  • Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which patient is disease-free for ≥ 5 years without further treatment.
  • Have a known hypersensitivity to any of the excipients of pirtobrutinib or to any intended study medications.
  • Persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure (guardianship, curatorship, legal protection), persons under psychiatric care
  • Treatment with another investigational agent or participating in another trial within 30 days prior to entering the study
  • No affiliate to social security
  • Currently pregnant (confirmed with positive pregnancy test) or breast feeding.
  • Women of Childbearing Potential (WOCBP) unless the following criteria are met- a negative pregnancy test is required for all WOCBP within 21 days before start of study intervention, followed by immediate highly effective contraception; further pregnancy testing will be performed monthly.
  • Fertile men or WOCBP unless the following criteria are met:
  • Willing to use 2 methods of reliable contraception, including one highly effective contraceptive method (Pearl Index < 1) and one additional effective (barrier) method during study intervention and for 1 month after last pirtobrutinib dose (for WOCBP). Men must refrain from sperm donation during the study.
  • Fertile male and female patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study.
  • Lactation or plan to breastfeed during the study or within 1 week of the last dose of study treatment.

About this study

Official title: Fixed Duration Treatment With Combined Pirtobrutinib and Short Course Immuno-chemotherapy in Fit Patients With Previously Untreated Symptomatic Chronic Lymphocytic Leukemia (CLL). A Phase II FILO Trial

The evidence base in support of fixed-duration, first-line approaches in medically fit patients with CLL is clearly strengthening, whether through combining targeted agents with immunochemotherapy or through chemotherapy-free combinations. The long-term PB MRD response rates with the investagators fixed-duration (15-month) immunochemotherapy approach remain the best to date, even compared to the new targeted agent combinations of ibrutinib-venetoclax or obinutuzumab-venetoclax.

The investigators' phase 2 ICLL07 trial in previously untreated fit CLL patients with a fixed-duration immunochemotherapy approach (with 4 cycles of FC-obinutuzumab and chemosparing strategy) carries a low risk for short and long term toxicities which still exist, including cardiac toxicities probably related to BTK inhibitors, moreover, two patients experienced treatment related myelodysplastic syndrome or acute myeloid leukemia beyond the end of treatment. Follow-up at 5,5 years from treatment start showed a persistent PB MRD benefit beyond end of treatment, high survival rates, and low long term toxicity with no difference in the durability of MRD response between the mutated and unmutated IGHV patients.

Read more

The investigators aim to explore the safety and efficacy of a fixed duration strategy combining a new BTK inhibitor with a favorable safety profile and a limited number of ICT courses.

The main goals and concerns are:

  1. to ensure deep response and long lasting MRD ii) to reduce the duration of BTKi exposure and the risk of clonal evolution with the appearance of deleterious mutations iii) to limit the risk of hematopoietic secondary cancers (MDS/AML) by excluding patients in whom clonal hematopoiesis of undetermined potential (CHIP) is detected before inclusion and decreasing the number of courses of chemotherapy to 3 cycles. Moreover, patients with TP53 abnormalities will be excluded with a lower cut off (1% versus 10% in the previous studies) iv) to limit the risk of BTKi toxicity by using a non-covalent BTKi
Being tested
Pirtobrutinib, Fludarabine, Cyclophosphamide, Obinutuzumab
Medical subject headings
Leukemia, B-Cell

What participants receive

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

  • PirtobrutinibDrug

    Pirtobrutinib 200 mg QD should be taken at a consistent time on each day for 15 cycles (C1-C15) for oral use.

    Dosing is intended to be fixed (i.e., not weight-based or BSA-based). Pirtobrutinib may be taken with food or drink but should be taken as consistently as possible. No fasting is required for pirtobrutinib. Refer to Section 10.1.5 for 10.1.5. for prohibited concomitant medication Patients must keep a daily dosing diary to record dosing compliance of oral study treatment by pirtobrutinib.

    Late doses (i.e., 4 or more hours after scheduled time) should be noted in the dosing diary. Doses late by more than 6 12 hours should not be made up and recorded in the dosing diary as missed. Reasons should be recorded for any missed dose. Vomiting after dosing should be noted in the dosing diary and a vomited dose should not be redosed or replaced.

    Patients will continue pirtobrutinib dosing until PD, unacceptable toxicity, or other reason for treatment discontinuation

  • FludarabineDrug

    All patients will receive 3 cycles of FCO administered at 4 weeks intervals (D1 = D29) from cycles 10, 11 and 12.

    Fludarabine: 40 mg/m² per os, D2 to D4

  • CyclophosphamideDrug

    All patients will receive 3 cycles of FCO administered at 4 weeks intervals (D1 = D29) from cycles 10, 11 and 12.

    Cyclophosphamide: 250 mg/m² per os, D2 to D4

  • ObinutuzumabDrug

    All patients will receive 3 cycles of FCO administered at 4 weeks intervals (D1 = D29) from cycles 10, 11 and 12.

    Obinutuzumab: 1000 mg at D1, D8, D15

    Obinutuzumab could be splited for the cycles 1 (100 mg Day 1 + 900 mg Day 2) according to the bulky disease (risk of infusion rate and tumor lysis syndrome).

    A premedication including an antihistamine (e.g. dexchlorpheniramine; 5 mg IV) and paracetamol (1000 mg, IV) and methylprednisolone 1 mg/kg IV will be administered 30 min prior to the administration of the obinutuzumab infusion

Study groups in NCT07624799
Study groupRoleWhat they receive
Single ArmExperimentalNot described
Receives: Drug: Pirtobrutinib; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Obinutuzumab

What is being measured

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

  1. Peripheral blood with undetectable (<10-4) minimal residual disease at month 24

    Measured: month 24

Secondary outcomes (2)

  1. PB MRD at month 9 and 18 and BM MRD at month 24

    Measured: month 9, 18 and 24

  2. Progression free survival (PFS), disease-free survival (DFS), event-free survival (EFS), overall survival (OS) and time to next treatment (TTNT)

    Measured: End of study

Timeline

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

  1. First posted3 Jun 2026
  2. Study start1 Sep 2026 (estimated)
  3. Primary completion1 Sep 2028 (estimated)
  4. Study completion1 Sep 2033 (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
82 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07624799
Sponsor's protocol ID
FILOCLL016-PACIFIC
Other IDs
2025-521199-80-00, 2025
Acronym
PACIFIC
Status last verified
May 2026
First submitted
25 Nov 2025
Last updated
3 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pirtobrutinib, Fludarabine and Cyclophosphamide in people with CLL (Chronic Lymphocytic Leukemia), run by French Innovative Leukemia Organisation.

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 19 inclusion and 45 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: opening soon, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

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?

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?

Peripheral blood with undetectable (<10-4) minimal residual disease at month 24 (time frame: month 24). 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 NCT07624799.

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 Jun 2026.

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