Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
Condition(s) studied
Investigational drug(s) / intervention(s)
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.
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.
Study summary
The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20). Epcoritamab will be tested either in
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.
Eligibility
Primary outcome measure(s)
- Dose Escalation Phase and Safety Run-in (R/R CLL arm): Number of Participants with Dose Limiting Toxicities (DLTs) — During the first cycle for low dose cohorts (Cycle length = 28 days) and for high dose cohorts (Cycle length = 35 days)
DLT events were defined as clinically significant adverse events (AEs) or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications as assessed per Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0. - Dose Escalation Phase and Safety Run-in: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) — Up to 5 years
- Dose Escalation Phase: Number of Participants with Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and Clinical Tumor Lysis Syndrome (CTLS) — Up to 5 years
CRS and ICANS will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria. CTLS will be graded according to Cairo-Bishop criteria. - Expansion Phase: Overall Response Rate (ORR) — Up to 5 years
R/R CLL participants will be assessed according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and the RS participants according to Lugano criteria. ORR based on the Lugano criteria is defined as the percentage of participants who achieve a response of PR or complete remission (CR), prior to initiation of subsequent therapy. The ORR based on the iwCLL criteria is defined as the percentage of participants who achieve a response of PR, CR with incomplete bone marrow recovery (CRi), or CR, prior to the initiation of subsequent therapy.
Trial sites (81)
| Facility | City | Region | Status |
|---|---|---|---|
| O'Neal Comprehensive Cancer Center at University of Alabama at Birmingham | Birmingham | Alabama | |
| University of California Davis Medical Center Sacramento | California City | California | |
| City of Hope National Medical Center | Duarte | California | |
| Cedars-Sinai Medical Center | Los Angeles | California | |
| David Geffen School of Medicine | Los Angeles | California | |
| Stanford Cancer Center | Palo Alto | California | |
| Mount Sinai Comprehensive Cancer Center | Miami Beach | Florida | |
| Memorial Healthcare System | Pembroke Pines | Florida | |
| National Institutes of Health | Bethesda | Maryland | |
| Massachusetts General Hospital | Boston | Massachusetts | |
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | |
| Henry Ford Medical Group | Detroit | Michigan | |
| Hackensack Meridian Hospital | Hackensack | New Jersey | |
| Northwell Health Cancer Institute | Lake Success | New York | |
| Columbia University Herbert Irving Comprehensive Cancer Center | New York | New York | |
| Memorial Sloan Kettering Cancer Center | New York | New York | |
| Duke University Medical Center | Durham | North Carolina | |
| University of Cincinnati | Cincinnati | Ohio | |
| The Ohio State University Comprehensive Cancer Center | Columbus | Ohio | |
| University of Pennsylvania School of medicine | Philadelphia | Pennsylvania | |
| The University of Texas Southwestern Medical Centre | Dallas | Texas | |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | |
| Fred Hutchinson Cancer Research Center | Seattle | Washington | |
| St. George Hospital | Kogarah | New South Wales | |
| Flinders Medical Centre | Bedford Park | South Australia | |
| Barwon Health | Geelong | Victoria | |
| Peter MacCallum Cancer Centre | Melbourne | Victoria | |
| Alfred Health | Melbourne | Victoria | |
| AZ Sint-Jan | Bruges | Belgium | |
| Universitair Ziekenhuis Gent | Ghent | Belgium | |
| UZ Leuven | Leuven | Belgium | |
| Fakultni nemocnice Brno | Brno | Czechia | |
| Fakultni nemocnice Olomouc | Olomouc | Czechia | |
| Vseobecna Fakultni Nemocnice | Prague | Nové Město | |
| Fakultni nemocnice Hradec Kralove | Hradec Králové | Nový Hradec Králové | |
| Fakultni Nemocnice Ostrava | Ostrava | Poruba | |
| Rigshospitalet | Copenhagen | Capital Region | |
| Aalborg University Hospital | Aalborg | Denmark | |
| Århus University Hospital | Aarhus | Denmark | |
| Odense University Hospital | Odense | Denmark |
+ 41 more sites — see the full list on the official registry below.
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT04623541 on ClinicalTrials.gov ↗ ← All trials in the USA