Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
NCT ID: NCT04623541
Last Updated: 2026-01-07
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
424 participants
INTERVENTIONAL
2020-11-25
2028-04-30
Brief Summary
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Relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as:
* Monotherapy, or
* Combination therapy:
* epcoritamab + venetoclax
* epcoritamab + pirtobrutinib
In Non-United States (US) Participants Only: Treatment-naïve (TN) high risk (HR) (CLL):
• epcoritamab + pirtobrutinib
Combination therapy for Richter's Syndrome (RS):
* epcoritamab + lenalidomide
* epcoritamab + R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine \[Oncovin®\] and prednisone).
The study includes participants with R/R or TN HR CLL (non-US participants only)/small lymphocytic lymphoma (SLL) and participants with RS.
The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Participants with RS are only included in the expansion phase.
Epcoritamab will be injected subcutaneously (under the skin). Standard-of-care and combination treatments (venetoclax, pirtobrutinib, lenalidomide, and R-CHOP) will be given either orally (by mouth) or intravenously (in a vein).
Study details include:
* Study duration will be up to 5 years after the last participant's first treatment in the trial.
* The treatment duration for each participant will be between 12 months (1 year) and 24 months (2 years), depending upon the treatment arm assigned.
* The visit frequency will be either weekly, every other week, or monthly, depending upon the part of the study.
All participants will receive active drug; no one will be given placebo.
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Detailed Description
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The purpose of the expansion phase is to assess and evaluate the preliminary efficacy, safety and tolerability profiles of epcoritamab monotherapy, epcoritamab + venetoclax and epcoritamab + pirtobrutinib at the RP2D for participants with R/R CLL, TN HR CLL (in non-US participants only) and SLL. Along with this, epcoritamab monotherapy, epcoritamab + lenalidomide and epcoritamab + R-CHOP will be evaluated in participants with RS to assess their efficacy, safety and tolerability profiles.
The purpose of safety run-in phase for pirtobrutinib combination therapy is to evaluate the safety and tolerability profiles of pirtobrutinib in combination with epcoritamab.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Epcoritamab in R/R CLL/SLL
In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase.
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days, (except Cycle 1 for high-dose cohorts = 35 days).
Epcoritamab in RS
Only in expansion phase.
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days.
Epcoritamab + Venetoclax in R/R CLL/SLL
In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase.
Venetoclax
Venetoclax tablets will be administered orally once daily during the 5-week ramp up period in cycles of 28 or 35 days each.
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days, (except Cycle 1 for high-dose cohorts = 35 days).
Epcoritamab + Lenalidomide in RS
Only in expansion phase.
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days.
Lenalidomide
Lenalidomide capsules will be administered once daily for 21 days in each cycle of 28 days.
Epcoritamab + R-CHOP in RS
Only in expansion phase.
rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
R-CHOP will be administered intravenously (prednisone may be administered orally) in cycles of 21 days.
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 21 days and 28 days.
Epcoritamab + Pirtobrutinib in R/R CLL, TN HR CLL (Non-US Participants Only) and SLL
Safety run-in and expansion phases.
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days.
Pirtobrutinib
Pirtobrutinib tablets will be administered in cycles of 28 days.
Fixed Duration Epcoritamab in R/R CLL/SLL
Only in expansion phase.
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days.
Interventions
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rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
R-CHOP will be administered intravenously (prednisone may be administered orally) in cycles of 21 days.
Venetoclax
Venetoclax tablets will be administered orally once daily during the 5-week ramp up period in cycles of 28 or 35 days each.
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days.
Lenalidomide
Lenalidomide capsules will be administered once daily for 21 days in each cycle of 28 days.
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days.
Pirtobrutinib
Pirtobrutinib tablets will be administered in cycles of 28 days.
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days.
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days, (except Cycle 1 for high-dose cohorts = 35 days).
Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 21 days and 28 days.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Evidence of CD20 positivity in a sample representative of the disease at Screening.
3. Acceptable hematology parameters and organ function based on baseline bloodwork.
4. Life expectancy \>3 months on standard of care (SOC) for CLL, \>3 months for RS.
5. For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
6. For R/R CLL monotherapy arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor or at least 1 prior line of systemic antineoplastic therapy, including treatment with (or intolerance of) a covalent BTK inhibitor (cBTKi) and a B-cell lymphoma 2 (BCL-2) inhibitor.
7. For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
8. For all RS arms - Must have measurable disease by fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) or magnetic resonance imaging (MRI) scan.
9. For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
10. For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
11. For RS - lenalidomide combination therapy arm
* Deemed as ineligible for chemoimmunotherapy at the investigator's discretion, or participant who refuses to receive intensive chemotherapy.
* Eligible for treatment with lenalidomide.
* Must be willing to use contraception and adhere to the Lenalidomide Pregnancy Risk Minimization Plan
* A woman must agree not to breastfeed a child during treatment and for at least 28 days after discontinuation from study.
12. For RS - R-CHOP combination Therapy Arm -
* Eligible for treatment with R-CHOP.
* Females of childbearing potential must use highly effective contraceptive measures while taking R-CHOP and for 12 months after stopping treatment.
* A woman must agree not to breastfeed a child during treatment or until 12 months after last treatment.
13. For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy.
* Presence of measurable disease.
* Must take prophylaxis for tumor lysis syndrome (TLS).
14. For R/R CLL pirtobrutinib combination Therapy arm:
* Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
* Presence of measurable disease.
* Previous treatment with at least one and a maximum 3 prior lines of therapy including a cBTKi.
* Diagnosis of CLL/SLL that met published iwCLL criteria.
15. Non-US Participants Only - Participants with TN HR CLL - Pirtobrutinib Combination Therapy Expansion:
* Diagnosis of CLL/SLL that met published iwCLL criteria 2018.
* Must have active CLL/SLL disease that needs treatment per iwCLL
* Must take prophylaxis for TLS based on their TLS risk evaluation upon initiation of trial drug.
* Must have one or more high-risk features.
* Presence of measurable disease.
Exclusion Criteria
2. Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
3. Received chimeric antigen receptor (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of trial drug.
4. Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
5. Received vaccination with live vaccines within 28 days.
6. Clinically significant cardiac disease.
7. Known current malignancy other than inclusion diagnosis.
8. Has had major surgery within 4 weeks.
9. Known history of human immunodeficiency virus (HIV).
10. For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
11. For R/R CLL - Venetoclax Combination Therapy arm: received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial or has progressed on venetoclax treatment.
12. For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
13. RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS.
14. R/R CLL - Pirtobrutinib Combination Therapy Arm - Prior exposure to a non-covalent (reversible) BTK inhibitor or a BTK degrader.
15. Pirtobrutinib Combination Therapy Expansion Arms:
* History of bleeding disorders or participants requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist
* Require continuous treatment with or have received strong cytochrome P450 (CYP) 3A inhibitors or strong/moderate CYP3A inducers within 4 to 5 half-lives or 14 days prior to the first dose of pirtobrutinib.
18 Years
ALL
No
Sponsors
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AbbVie
INDUSTRY
Eli Lilly and Company
INDUSTRY
Genmab
INDUSTRY
Responsible Party
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Locations
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O'Neal Comprehensive Cancer Center at University of Alabama at Birmingham
Birmingham, Alabama, United States
University of California Davis Medical Center Sacramento
California City, California, United States
City of Hope National Medical Center
Duarte, California, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
David Geffen School of Medicine
Los Angeles, California, United States
Stanford Cancer Center
Palo Alto, California, United States
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States
Memorial Healthcare System
Pembroke Pines, Florida, United States
National Institutes of Health
Bethesda, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Henry Ford Medical Group
Detroit, Michigan, United States
Hackensack Meridian Hospital
Hackensack, New Jersey, United States
Northwell Health Cancer Institute
Lake Success, New York, United States
Columbia University Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
University of Cincinnati
Cincinnati, Ohio, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Pennsylvania School of medicine
Philadelphia, Pennsylvania, United States
The University of Texas Southwestern Medical Centre
Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
St. George Hospital
Kogarah, New South Wales, Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia
Barwon Health
Geelong, Victoria, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Alfred Health
Melbourne, Victoria, Australia
AZ Sint-Jan
Bruges, , Belgium
Universitair Ziekenhuis Gent
Ghent, , Belgium
UZ Leuven
Leuven, , Belgium
Vseobecna Fakultni Nemocnice
Prague, Nové Město, Czechia
Fakultni nemocnice Hradec Kralove
Hradec Králové, Nový Hradec Králové, Czechia
Fakultni Nemocnice Ostrava
Ostrava, Poruba, Czechia
Fakultni nemocnice Brno
Brno, , Czechia
Fakultni nemocnice Olomouc
Olomouc, , Czechia
Rigshospitalet
Copenhagen, Capital Region, Denmark
Aalborg University Hospital
Aalborg, , Denmark
Århus University Hospital
Aarhus, , Denmark
Odense University Hospital
Odense, , Denmark
Roskilde Sygehus
Roskilde, , Denmark
Vejle Sygehus
Vejle, , Denmark
CHU de Montpellier Hôpital Saint Eloi
Montpellier, Cedex 5, France
CHU Hôpital Haut-Lévêque Bordeaux
Pessac, Gironde, France
CHU Hôpital de Brabois Nancy
Vandœuvre-lès-Nancy, Meurthe Et Moselle, France
Hôpital Privé du Confluent
Nantes, Pays de la Loire Region, France
CHU Clermont Ferrand
Clermont-Ferrand, Puy De Dome, France
Hôpital Saint-Louis
Paris, , France
Hôpital Universitaire Pitié-Salpêtrière
Paris, , France
Universitaetsklinikum Ulm
Ulm, Baden-Wurttemberg, Germany
Universitaetsklinikum Koeln
Cologne, , Germany
Universitaetsklinikum Schleswig-Holstein- Karl-Lennart-Krebscentrum
Kiel, , Germany
Bnai Zion Medical Center
Haifa, , Israel
Hadassah University Hospital - Ein Kerem
Jerusalem, , Israel
Rabin Medical Center-Beilinson Campus
Petah Tikva, , Israel
Chaim Sheba Medical Center
Ramat Gan, , Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, , Israel
Istituto di Candiolo
Torino, Candiolo, Italy
AOU Arcispedale Sant'Anna
Ferrara, Cona, Italy
IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST
Meldola, Forli - Cesena, Italy
IRCCS Policlinico Universitario Agostino Gemelli
Rome, Lazio, Italy
AOU Policlinico Sant'Orsola Malpighi IRCCS
Bologna, , Italy
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
Brescia, , Italy
Ospedale San Raffaele
Milan, , Italy
Ospedale Maggiore di Novara
Novara, , Italy
AOU Policlinico Umberto I
Roma, , Italy
AOU Città della Salute e della Scienza di Torino
Torino, , Italy
Maastricht University Medical Center
Maastricht, Limburg, Netherlands
Albert Schweitzer Ziekenhuis, Dordwijk
Dordrecht, South Holland, Netherlands
Amsterdam UMC
Amsterdam, , Netherlands
Universitair Medisch Centrum Groningen
Groningen, , Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, , Netherlands
Pratia Medical Center Katowice (Centrum Medyczne Pratia Katowice)
Katowice, , Poland
Pratia Malopolskie Medical Center Krakow (Pratia Małopolskie Centrum Medyczne Krakow)
Krakow, , Poland
Aidport sp z o.o.
Skorzewo, , Poland
ICO Badalona - Hospital Universitario Germans Trias Pujol
Badalona, Barcelona, Spain
AOC Arcispedale Saint'Anna
Coaña, Ferarra, Spain
Hospital Clinico Universitario de Valencia
Valencia, València, Spain
Hospital Clinic de Barcelona
Barcelona, , Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, , Spain
Hospital Universitario Ramón y Cajal
Madrid, , Spain
Hospital Universitario Fundacion Jiménez Díaz
Madrid, , Spain
Hospital Universitario Virgen Macarena
Seville, , Spain
Royal Cornwall Hospital
Truro, Cornwall, United Kingdom
Nottingham University Hospitals City Campus
Nottingham, Nottinghamshire, United Kingdom
St. James s University Hospital
Leeds, West Yorkshire, United Kingdom
Barts Hospital
London, , United Kingdom
Countries
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Central Contacts
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References
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Kater AP, Janssens A, Eradat H, Offner F, Sandoval-Sus JD, Shadman M, Poulsen CB, Christensen JH, Thompson MC, Guan M, Steele AJ, Rios M, Holst Morch M, Oki T, Valentin R, Bellido M, Eichhorst B. Epcoritamab monotherapy for Richter transformation (EPCORE CLL-1): findings from a single-arm, multicentre, open-label, phase 1b/2 trial. Lancet Haematol. 2025 Dec 8:S2352-3026(25)00327-8. doi: 10.1016/S2352-3026(25)00327-8. Online ahead of print.
Other Identifiers
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2020-000848-57
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
NL74221.056.20
Identifier Type: REGISTRY
Identifier Source: secondary_id
MOH_2023-04-02_012496
Identifier Type: REGISTRY
Identifier Source: secondary_id
2023-504828-25-00
Identifier Type: CTIS
Identifier Source: secondary_id
1006575
Identifier Type: OTHER
Identifier Source: secondary_id
RECF-005228
Identifier Type: OTHER
Identifier Source: secondary_id
GCT3013-03
Identifier Type: -
Identifier Source: org_study_id
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