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A Prospective, Open-label, Randomized, Multicenter Phase-III Trial to Evaluate the Efficacy of Pirtobrutinib and Epcoritamab Compared With R-(Mini)-CHOP for Treatment of Patients With DLBCL-type Richter Transformation (CLLRT2)

28 oktober 2026 bijgewerkt door: German CLL Study Group

The aim of the trial is to Evaluate the Efficacy of Pirtobrutinib and Epcoritamab Compared With R-(Mini)-CHOP for Treatment of Patients With DLBCL-type Richter Transformation

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

This trial is a phase 2 study and - according to the definitions of the ICH Harmonized Tripartite Guide-line E8 - a therapeutic exploratory type of study, which is designed as a prospective, multicenter, open label trial. The trial aims to investigate the efficacy and safety of a fixed-duration treatment ap-proach in patients aged 80 years or older and/or those exhibiting symptoms of frailty.

Studietype

Ingrijpend

Inschrijving (Geschat)

116

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Australië
      • Melbourne, Australië, 3000
  • Denemarken
      • Copenhagen, Denemarken, 2100
  • Duitsland
      • Cologne, Duitsland, 50937
      • Dresden, Duitsland, 01307
        • Nog niet aan het werven
        • Technische Universitaet Dresden
        • Contact:
      • Frankfurt, Duitsland, 60590
      • Heidelberg, Duitsland, 69120
      • Kiel, Duitsland, 24105
        • Nog niet aan het werven
        • Universitätsklinikum Schleswig-Holstein Campus Kiel
        • Contact:
      • Ulm, Duitsland, 89081
  • Ierland
      • Dublin, Ierland, Dublin 9
      • Galway, Ierland, H91 YR71
        • Werving
        • University Hospital Galway
        • Contact:
  • Oostenrijk
      • Innsbruck, Oostenrijk, 6020
        • Nog niet aan het werven
        • Medizinische Universitaet Innsbruck
        • Contact:
      • Vienna, Oostenrijk, 1090

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  1. Age ≥80 years OR considered frail defined by a frailty score of >2 on the FRAIL scale via the patient´s assessment

  2. Has documented treatment-naïve CLL or small lymphocytic lymphoma (SLL) according to iwCLL 2018 criteria3

  3. CLL/SLL requiring treatment according to the iwCLL 2018 criteria3

  4. Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as follows, unless cytopenia is due to marrow involvement of CLL:

    • Absolute neutrophil count ≥ 1.0 × 10^9/L
    • Platelet counts ≥ 30 × 10^9/L; in cases of thrombocytopenia clearly due to marrow in-volvement of CLL (per the discretion of the investigator); platelet count should be ≥ 10 × 10^9/L if there is bone marrow involvement
    • Total haemoglobin ≥ 9 g/dL (without transfusion support, unless anaemia is due to mar-row involvement of CLL)

  5. Adequate liver function as indicated by a total bilirubin, AST, and ALT ≤2 times the institutional upper limit of normal (ULN) value unless directly attributable to the patient's CLL or Gilbert's syndrome

  6. Adequate renal function defined by a value ≥30 mL/min, determined either by creatinine clearance directly measured with a 24-hour urine collection or via estimated GFR calculated according to the CKD-EPI equation or Cystatin C measurements (e.g. in sarcopenic patients).

  7. Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed repeatedly until 6 months after last month of treatment), negative testing for hepa-titis C RNA within 6 weeks prior to registration

  8. Life expectancy ≥ 3 months

  9. In case of a recent previous (i.e. debulking) treatment, patients must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods be-fore start of the study treatment in the CLL-Frail2 trial:

    • chemotherapy ≥ 28 days
    • antibody treatment ≥ 14 days
    • corticosteroids may be applied until the start of the study therapy; these have to be re-duced to an equivalent of ≤ 20mg prednisolone per day during treatment

  10. Signed informed consent and, in the investigator's judgment, able to comply with the study protocol

  11. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

  • 1. Previous CLL-directed therapies 2. Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leu-kaemia) 3. Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML) 4. Uncontrolled autoimmune condition 5. Malignancies other than CLL currently requiring systemic therapies (unless the malignant dis-ease is in a stable remission at the discretion of the treating physician) 6. Uncontrolled infection currently requiring systemic treatment 7. Any serious medical condition or abnormality in clinical laboratory tests that, in the investiga-tor's judgment, precludes the patient's safe participation in and completion of the study 8. Requirement of treatment with any moderate or strong CYP3A4 inhibitor or strong CYP3A4 inducer (≤ 14 days or 5 half-lives, whichever is shorter) before the first dose of study drug, or requiring ongoing treatment with a moderate or strong CYP3A inhibitor or a strong CYP3A in-ducer.

    9. Requirement of therapy with phenprocoumon or other vitamin K antagonists 10. Known active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:

    • Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU), and if they are willing to undergo monitoring for HBV reactivation

    • Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable 11. Major surgery within 4 weeks of the first dose of study drug 12. Any uncontrolled or clinically significant cardiovascular disease including the following:

    • New York Heart Association class III or IV congestive heart failure

    • History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricu-lar fibrillation, torsades de pointes) 13. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand dis-ease if not CLL/SLL related, or history of spontaneous bleeding requiring blood transfusion or other medical intervention 14. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery proce-dures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

      15. Use of investigational agents, e.g. monoclonal antibodies or other experimental drugs within clinical trials, which might interfere with the study drug within 28 days (or 5 times half-life [t1/2] of the compound, whichever is longer) prior to registration 16. Known hypersensitivity to zanubrutinib or sonrotoclax or any of the excipients 17. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment) 18. Fertile men or women of childbearing potential unless:

    • surgically sterile or ≥ 2 years after the onset of menopause, or

    • willing to use two methods of reliable contraception including one highly effective contra-ceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 7 days after sonrotoclax and 30 days after zanubrutinib respec-tively 19. Vaccination with a live vaccine <28 days prior to registration 20. Legal incapacity 21. Prisoners or subjects who are institutionalized by regulatory or court order 22. Persons who are in dependence to the sponsor or an investigator

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: Arm A: R-(mini)-CHOP

Cycle 1-6 Day 1: Cyclophosphamide 750 mg/m2 iv Doxorubicin 50 mg/m2 iv Vincristine 1.4 mg/m2 (max 2 mg) iv Rituximab 375 mg/m2 iv Day 1-5: Prednisolone 100 mg po

If R-CHOP-ineligible*, R-mini-CHOP3 is administered:

Cycle 1-6 Day 1: Cyclophosphamide 400 mg/m2 iv Doxorubicin 25 mg/m2 iv Vincristine 1 mg iv Rituximab 375 mg/m2 iv or sc Day 1-5: Prednisolone 100 mg po
Geneesmiddel: Cyclophosphamide

750 mg/m2 iv (R-CHOP) or 400 mg/m2 iv (R-mini-CHOP)

Geneesmiddel: Doxorubicin

50 mg/m2 iv (R-CHOP) or 25 mg/m2 iv (R-mini-CHOP)

Geneesmiddel: Vincristine

1.4 mg/m2 iv (R-CHOP) or 1 mg/m2 iv (R-mini-CHOP)

Geneesmiddel: Rituximab

375 mg/m2 iv (R-CHOP) or 375 mg/m2 iv or sc (R-mini-CHOP)
Experimenteel: Arm B: Epcoritamab-Pirtobrutinib

12 cycles: Cycle 1 Day 1-21: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 0.16 mg sc Day 8: Epcoritamab 0.8 mg sc Day 15: Epcoritamab 48 mg sc

Cycle 2-4 Day 1-21: Pirtobrutinib 200 mg QD po Day 1, 8, 15: Epcoritamab 48 mg sc

Cycle 5+6 Day 1-21: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 48 mg sc

Cycle 7-12:

Day 1-28: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 48 mg sc

For patients with CR, PR or SD after 12 cycles (=EO[C]T), maintenance treatment with pirtobrutinib 200 mg QD until unacceptable toxicity, disease progression or allogeneic stem cell transplantation will be offered.
Biologisch: Epcoritamab

Cycle 1 Day 1-21: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 0.16 mg sc Day 8: Epcoritamab 0.8 mg sc Day 15: Epcoritamab 48 mg sc

Cycle 2-28 Epcoritamab 48 mg sc

Andere namen:
  • Epkinly®
Geneesmiddel: Pirtobrutinib

Pirtobrutinib 200 mg QD po

Andere namen:
  • Jaypirca®

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
PFS
Tijdsspanne: approx. 40 months after first subject in

Investigator-assessed progression-free survival (PFS) according to Lugano criteria
approx. 40 months after first subject in

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
ORR
Tijdsspanne: approx. 40 months after first subject in

Overall response rate (ORR) at the end of (combination) treatment according to Lugano criteria
approx. 40 months after first subject in
CRR
Tijdsspanne: approx. 40 months after first subject in

Complete response rate (CRR) at the end of (combination) treatment according to Lugano criteria
approx. 40 months after first subject in
Best response according to Lugano criteria
Tijdsspanne: approx. 40 months after first subject in

Best response according to Lugano criteria
approx. 40 months after first subject in
Undetectable minimal residual disease (uMRD)
Tijdsspanne: approx. 40 months after first subject in

Undetectable minimal residual disease (uMRD) rates in peripheral blood at the end of (combination) treatment
approx. 40 months after first subject in
DOR
Tijdsspanne: approx. 40 months after first subject in

Duration of response (DOR) according to Lugano criteria
approx. 40 months after first subject in
Overall survival (OS)
Tijdsspanne: approx. 40 months after first subject in

Overall survival (OS)
approx. 40 months after first subject in
TTNT
Tijdsspanne: approx. 40 months after first subject in

Time to next treatment (TTNT)
approx. 40 months after first subject in
TFS
Tijdsspanne: approx. 40 months after first subject in

Treatment-free survival (TFS)
approx. 40 months after first subject in
SCT
Tijdsspanne: approx. 40 months after first subject in

Proportion of patients receiving allogeneic stem cell transplantation (SCT) for consolidation
approx. 40 months after first subject in

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

German CLL Study Group

Medewerkers

Nordic CLL Study Group (NCLLSG)
The Australasian Leukaemia & Lymphoma Group (ALLG)
Cancer Trials Ireland (CTI)
Fondazione GIMEMA

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

18 juni 2026

Primaire voltooiing (Geschat)

15 mei 2030

Studie voltooiing (Geschat)

15 mei 2030

Studieregistratiedata

Eerst ingediend

28 oktober 2026

Eerst ingediend dat voldeed aan de QC-criteria

28 oktober 2026

Eerst geplaatst (Werkelijk)

5 november 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

5 november 2026

Laatste update ingediend die voldeed aan QC-criteria

28 oktober 2026

Laatst geverifieerd

1 oktober 2026

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • CLLRT2

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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