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HOVON 180 CLL: Treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma with 24 cycles of pirtobrutinib in combination with 12 cycles of epcoritamab if the disease comes back after previous treatment.
EU CTIS ID: 2025-524842-89-00
What this study is testing
Safety Run-In: To evaluate the safety and tolerability of initiating epcoritamab in combination with pirtobrutinib following three cycles of pirtobrutinib monotherapy. Cohort Expansion: To evaluate efficacy in terms of PFS at 24 months after first dose of pirtobrutinib.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Documented relapsed or refractory CLL or SLL (SLL in Cohort Expansion only) following at least one systemic 1st-line treatment
- Patient is able and willing to adhere to the study visit schedule and other protocol requirements
- Patient is capable of giving informed consent
- Written informed consent
- Requiring treatment according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
- Age at least 18 years
You likely can't join if
- The patient has received any of the following anticancer therapies: o Targeted therapies, investigational agents, therapeutic monoclonal antibodies, or cytotoxic chemotherapy within either: 5 drug half-lives, or 2 weeks prior to the first dose of study treatment, whichever is shorter, o Exception: Anti-CD20 monoclonal antibodies, covalent BTK inhibitors, and BCL2 inhibitors are permitted and may be continued up to the first dose of pirtobrutinib, o Immunoconjugated antibody treatment within 10 weeks or 5 half-lives, whichever is shorter, o Broad field radiation (≥ 30% of the bone marrow or whole brain radiotherapy) within 14 days, o Palliative limited field radiation within 7 days, o Prior treatment with a CD3 × CD20 bispecific antibody, o Prior treatment with pirtobrutinib within 24 months, o CAR-T-cell therapy within 100 days prior to first dose of study drug or need of anti-cytokine therapy for toxicity from CAR-T therapy and/or residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy
- Use of any other experimental drug or therapy within 28 days of registration
- Malignancies other than CLL/SLL unless in remission defined as treated non-melanoma skin cancer or other neoplasias treated curatively ≥ 1 year ago, without signs of progression and not requiring systemic therapies (with the exception of ongoing anti-hormonal therapy)
- Major surgery within 28 days prior to registration
- Pregnant women and nursing mothers
- Known central nervous system involvement
See the full eligibility criteria
Who can join
- Documented relapsed or refractory CLL or SLL (SLL in Cohort Expansion only) following at least one systemic 1st-line treatment
- Patient is able and willing to adhere to the study visit schedule and other protocol requirements
- Patient is capable of giving informed consent
- Written informed consent
- Requiring treatment according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
- Age at least 18 years
- Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status 0-2
- Adequate BM function defined as: Hemoglobin (Hb) >5 mmol/l or >8 g/dL. Absolute neutrophil count (ANC) >1.0 x 109/L (1,000/μL), Platelet count >30 x 109/L (30,000/μL)
- Estimated Glomerular Filtration Rate (eGFR) Modification of Diet in Renal Disease (MDRD) or estimated creatinine clearance (CrCl) ≥ 45 ml/min (Cockcroft-Gault)
- Adequate liver function as indicated: Serum aspartate transaminase (AS(A)T) and alanine transaminase (AL(A)T) ≤ 3.0 x upper limit of normal (ULN); Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or controlled autoimmune hemolytic anemia)
- Prothrombin time (PT)/International normal ratio (INR) <1.5x ULN and activated partial thromboplastin time (aPTT) <1.5 x ULN
- Patients must have negative serological testing for hepatitis B and C, defined as negative hepatitis B surface antigen (HBsAg) and negative hepatitis B core antibody (anti-HBc), as well as negative hepatitis C antibody. Please see the protocol for further explanation regarding this criterion
What rules you out
- The patient has received any of the following anticancer therapies: o Targeted therapies, investigational agents, therapeutic monoclonal antibodies, or cytotoxic chemotherapy within either: 5 drug half-lives, or 2 weeks prior to the first dose of study treatment, whichever is shorter, o Exception: Anti-CD20 monoclonal antibodies, covalent BTK inhibitors, and BCL2 inhibitors are permitted and may be continued up to the first dose of pirtobrutinib, o Immunoconjugated antibody treatment within 10 weeks or 5 half-lives, whichever is shorter, o Broad field radiation (≥ 30% of the bone marrow or whole brain radiotherapy) within 14 days, o Palliative limited field radiation within 7 days, o Prior treatment with a CD3 × CD20 bispecific antibody, o Prior treatment with pirtobrutinib within 24 months, o CAR-T-cell therapy within 100 days prior to first dose of study drug or need of anti-cytokine therapy for toxicity from CAR-T therapy and/or residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy
- Use of any other experimental drug or therapy within 28 days of registration
- Malignancies other than CLL/SLL unless in remission defined as treated non-melanoma skin cancer or other neoplasias treated curatively ≥ 1 year ago, without signs of progression and not requiring systemic therapies (with the exception of ongoing anti-hormonal therapy)
- Major surgery within 28 days prior to registration
- Pregnant women and nursing mothers
- Known central nervous system involvement
- Fertile men or women of childbearing potential (WOCBP) unless: (1) surgically sterile or ≥ 2 years after the onset of menopause; (2) willing to use a highly effective contraceptive method such as oral contraceptives, intrauterine device, sexual abstinence or combination of male condom with either cap, diaphragm, or sponge with spermicide (double barrier methods) during study treatment and for 4 months after last dose of epcoritamab and 5 weeks (women) or 3 months (men) after last dose of pirtobrutinib
- Patients who are planning egg donation (ova, oocytes) for the purposes of assisted reproduction or sperm donation during study treatment, until 4 months after last dose of epcoritamab and 5 weeks after last dose of pirtobrutinib for egg donation and 3 months after last dose of pirtobrutinib for sperm donation
- Current participation in other clinical trial and using study medication
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Prior allogeneic stem cell transplantation and/or solid organ transplantation
- CTCAE grade III-IV cardiovascular disease including but not limited to: Significant cardiovascular disease defined as: unstable angina or acute coronary syndrome within the past 3 months prior to treatment initiation or a history of myocardial infarction within 3 months prior to treatment initiation or, documented Left Ventricular Ejection Fraction (LVEF) by any method of ≤ 40% in the 12 months prior to treatment initiation, ≥ Grade 3 New York Heart Association (NYHA) functional classification system of heart failure, Uncontrolled or symptomatic arrhythmias; Screening 12-lead Electrocardiogram (ECG) showing a baseline QT (Q and T wave) interval as corrected by Fridericia’s formula (QTcF) >480 msec
- Patient with a history of confirmed progressive multifocal leukoencephalopathy (PML)
- Current autoimmune disease-requiring immunosuppressive therapy except for up to 20 mg daily prednisone or equivalent
- Known allergy to xanthine oxidase inhibitors and/or rasburicase
- Current seizure disorder requiring therapy
- Active tuberculose (TB) or history of completed treatment for active TB within the past 12 months
- Patient receiving anti-coagulation therapy (e.g. warfarin, vitamin K antagonists, phenprocoumon)
- History of severe allergic or anaphylactic reactions to anti CD20 monoclonal or bi-specific antibody therapy, or known significant allergy or intolerance to any component or excipient constituents of the study treatment (and their excipients) and/or other products in the same class
- History of bleeding diathesis
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) within 2 weeks prior to first dose of study treatment
- Known active cytomegalovirus (CMV) infection
- Transformation of CLL (Richter’s transformation)
- Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled: infection, auto-immune hemolysis, immune thrombocytopenia, diabetes, hypertension, hyperthyroidism or hypothyroidism etc.)
- Patient known to be Human Immunodeficiency Virus (HIV)-positive
- Stroke or intracranial hemorrhage within 6 months prior to registration
- Severe pulmonary dysfunction (CTCAE grade III-IV)
- Severe neurological or psychiatric disease (CTCAE grade III-IV)
- Neuropathy > CTCAE grade II
- Patient who has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
- Vaccination with live vaccines within 28 days prior to registration
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.