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Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
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 either be studied as: * Monotherapy, or * Combination therapy: * epcoritamab + venetoclax * epcoritamab + lenalidomide * epcoritamab + R-CHOP (i. e.
, rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine (Oncovin®) and prednisone). The study includes patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL)/small lymphocytic lymphoma (SLL) and patients with Richter's Syndrome (RS). Study participants with R/R CLL/SLL are treated either with epcoritamab as monotherapy or epcoritamab + venetoclax.
Study participants with RS are treated either with epcoritamab as monotherapy or epcoritamab + lenalidomide or epcoritamab + R-CHOP. The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Patients with RS are only included in the expansion phase.
Epcoritamab will be injected subcutaneously (under the skin). Standard-of-care and combination treatments (venetoclax, 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.
* The treatment duration for each participant will be between 18 months (1. 5 years) 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.
Study details:
The purpose of the dose-escalation phase of the trial is to determine the recommended phase 2 dose (RP2D) and the maximum tolerated dose (MTD; if reached) as well as establish the safety profile of epcoritamab monotherapy and epcoritamab + venetoclax in participants with R/R CLL. The purpose of the expansion phase is to assess and evaluate the preliminary efficacy, safety and tolerability profiles of epcoritamab monotherapy and epcoritamab + venetoclax at the RP2D for patients with R/R CLL/SLL. Along with this, epcoritamab monotherapy, epcoritamab + lenalidomide and epcoritamab + R-CHOP will be evaluated in patients with RS to assess their efficacy, safety and tolerability profiles.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2020-11-25
Primary completion: 2029-06-01
Study completion finish: 2029-08-01
Study type
TREATMENT
Phase
PHASE1
PHASE2
Trial ID
NCT04623541
Intervention or treatment
BIOLOGICAL: Epcoritamab
BIOLOGICAL: Epcoritamab
DRUG: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
DRUG: Venetoclax
BIOLOGICAL: Epcoritamab
DRUG: Lenalidomide
Conditions
- • Small Lymphocytic Lymphoma
- • Richter's Syndrome
- • Relapsed/Refractory Chronic Lymphocytic Leukemia
Find a site
Closest Location:
Peter MacCallum Cancer Centre
Research sites nearby
Select from list below to view details:
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Alfred Health
Melbourne, Victoria, Australia
St. George Hospital
Kogarah, New South Wales, Australia
Barwon Health
Geelong, Victoria, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Epcoritamab in R/R CLL/SLL
| BIOLOGICAL: Epcoritamab
|
EXPERIMENTAL: Epcoritamab in RS
| BIOLOGICAL: Epcoritamab
|
EXPERIMENTAL: Epcoritamab + Venetoclax in R/R CLL/SLL
| BIOLOGICAL: Epcoritamab
|
EXPERIMENTAL: Epcoritamab + Lenalidomide in RS
| BIOLOGICAL: Epcoritamab
|
EXPERIMENTAL: Epcoritamab + R-CHOP in RS
| BIOLOGICAL: Epcoritamab
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Dose Escalation Phase (R/R CLL arm): Number of Participants with Dose Limiting Toxicities (DLTs) | 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. | During the first cycle for low dose cohorts (Cycle length = 28 days) and for high dose cohorts (Cycle length = 35 days) |
Dose Escalation Phase: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Not Specified | From first dose until the end of the safety follow-up period (60 days after last dose) |
Dose Escalation Phase: Number of Participants with Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and Clinical Tumor Lysis Syndrome (CTLS) | 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. | From first dose until the end of the safety follow-up period (60 days after last dose) |
Expansion Phase: Overall Response Rate (ORR) | ORR is defined as the percentage of participants who achieve a response of partial response or complete response, prior to initiation of subsequent therapy. 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. | Up to 5 years |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Expansion Phase: Number of Participants with TEAEs and SAEs | Not Specified | From first dose until the end of the safety follow-up period (60 days after last dose) |
Dose Escalation Phase: ORR | ORR is defined as percentage of participants who achieve a response of partial response or complete response, prior to initiation of subsequent therapy as assessed by iwCLL criteria. | Up to 5 years |
Both Phases: Duration of Response (DOR) | DOR is defined among responders, as the time from the initial documentation of response to the date of disease progression or death, whichever occurs earlier. | Up to 5 years |
Both Phases: Number of Participants with Complete Remission (CR) / CR with Incomplete Bone Marrow Recovery (CRi) | CR and CRi for R/R CLL participants will be assessed according to iwCLL criteria and CR for the RS participants, according to Lugano criteria. | Up to 5 years |
Both Phases: Time to Response (TTR) | TTR is defined among responders, as the time between first dose of epcoritamab and the initial documentation of response. | Up to 5 years |
Both Phases: Progression Free Survival (PFS) | PFS is defined as the time from the first dosing date of epcoritamab and the date of disease progression or death, whichever occurs earlier. | Up to 5 years |
Both Phases: Overall Survival (OS) | OS is defined as the time from the first dosing date of epcoritamab and the date of death due to any cause. | Up to 5 years |
Both Phases: Time to Next Systemic Anti-cancer Therapy (TTNT) | TTNT is defined as the time from the first dosing date of epcoritamab to the first documented administration of subsequent systemic anticancer therapy. | Up to 5 years |
Both Phases: Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Sample (AUClast) in Epcoritamab | Not Specified | Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) |
Both Phases: AUC From Time Zero to Infinity (AUCinf) in Epcoritamab | Not Specified | Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) |
Both Phases: Maximum (Peak) Plasma Concentration (Cmax) in Epcoritamab | Not Specified | Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) |
Both Phases: Pre-dose (Trough) Concentrations (Cthrough) in Epcoritamab | Not Specified | Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) |
Both Phases: Time to Reach Cmax (Tmax) in Epcoritamab | Not Specified | Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) |
Both Phases: Elimination Half-life (T1/2) in Epcoritamab | Not Specified | Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) |
Both Phases: Total Body Clearance of Drug From Plasma (CL) in Epcoritamab | Not Specified | Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) |
Both Phases: Volume of distribution (Vd) in Epcoritamab | Not Specified | Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) |
Both Phases: Lymphoid Cells for Immunophenotyping | Evaluation of B cells, T cells and their activation | Up to 5 years |
Expansion Phase: Number of Participants with CRS, ICANS and CTLS | CRS and ICANS will be graded based on ASTCT criteria. CTLS will be graded according to Cairo-Bishop criteria. | From first dose until the end of the safety follow-up period (60 days after last dose) |
Expansion Phase: Percentage of Participants with Minimal Residual Disease (MRD) Negativity | MRD negativity rate, is defined as the proportion of participants with at least 1 undetectable MRD result according to the specific threshold, prior to initiation of subsequent therapy. | Up to 5 years |
Both Phases: Number of Participants with Anti-drug Antibodies (ADA) to Epcoritamab | Not Specified | Up to end of treatment period (Up to 2 years) |
Expansion Phase: Number of Participants with Partial Remission (PR)/Nodular Partial Remission (nPR) | nPR is defined as PR with residual nodules or suspicious lymphocytic infiltrates in participants who are in remission. nPR is only calculated for R/R CLL. | Up to 5 years |
Both Phases: Duration of MRD Negativity | The time from first achieving MRD negativity after start of treatment to the MRD conversion to positive. | Up to 5 years |
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