NCT05791409

Brief Summary

In this study, efficacy and safety of 2 regimens that combine the CD3-CD20 T cell engager epcoritamab with venetoclax will be tested in relapsed/refractory CLL and SLL patients. The trial starts with phase I part to establish the recommended dose level (RDL) of epcoritamab in the combination with venetoclax for the phase II trial.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
112

participants targeted

Target at P75+ for phase_1

Timeline
79mo left

Started Apr 2024

Longer than P75 for phase_1

Geographic Reach
4 countries

24 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress24%
Apr 2024Nov 2032

First Submitted

Initial submission to the registry

February 1, 2023

Completed
2 months until next milestone

First Posted

Study publicly available on registry

March 30, 2023

Completed
1 year until next milestone

Study Start

First participant enrolled

April 10, 2024

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2029

Expected
3.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2032

Last Updated

April 12, 2024

Status Verified

April 1, 2024

Enrollment Period

4.9 years

First QC Date

February 1, 2023

Last Update Submit

April 10, 2024

Conditions

CLL/SLL

Outcome Measures

Primary Outcomes (2)

  • • Recommended phase II dose (RP2D) for the combination of venetoclax and epcoritamab based on dose limiting toxicity (DLT)

    endpoint for phase I and both arms

    6-12 months

  • • Undetectable minimal residual disease <10-4 (uMRD) in BM in absence of progression according to IWCLL criteria at 12 weeks after cycle 26

    endpoint for phase II and both arms

    29 months

Secondary Outcomes (14)

  • • Minimal residual disease (MRD) status in PB at cycle 4, 6, 9, 12, 15, 18, 21, 24 and 12 weeks after cycle 26; following treatment: every 3 months for the first year, then every 6 months until relapse or until 6 years after registration

    6 years

  • • Progression free survival (PFS), defined as time from registration to the first occurrence of disease progression or death from any cause, whichever occurs first.

    6 years

  • Overall survival (OS), defined as the time from registration to death from any cause.

    6 years

  • Best overall response rate (ORR) defined as the proportion of patients with a complete response (CR), complete response with incomplete marrow recovery (CRi), or partial response (PR) according to IWCLL 2018 criteria.

    6 years

  • • Event free survival (EFS), defined as time from randomization to date start of next CLL treatment, progression or death, whichever comes first.

    6 years

  • +9 more secondary outcomes

Study Arms (2)

Arm A

EXPERIMENTAL

6 cycles epcoritamab + 26 cycles venetoclax

Drug: EpcoritamabDrug: Venetoclax

Arm B

EXPERIMENTAL

12 cycles epcoritamab + 26 cycles venetoclax

Drug: EpcoritamabDrug: Venetoclax

Interventions

EpcoritamabDRUG

Number of cycles of epcoritamab is either 6 (cycle 1-6) or 12 (cycle 1-12). Patients will be treated until they have received the total number of assigned treatment cycles or until progression, or severe toxicity, whichever comes first.

Arm AArm B
VenetoclaxDRUG

All patients will receive venetoclax cycle 1-26 (a 5 week ramp-up of venetoclax will precede the first cycle). Patients will be treated until they have received the total number of assigned treatment cycles or until progression, or severe toxicity, whichever comes first.

Arm AArm B

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Documented relapsed or refractory CLL or SLL (SLL in phase II part only) following at least one systemic 1st-line treatment
  • Requiring treatment according to IWCLL criteria (appendix A);
  • Age at least 18 years;
  • ECOG/WHO performance status 0-2;
  • In case of prior venetoclax treatment, enrollment can only occur at least 24 months after end of treatment and patients must not have progressed during venetoclax treatment;
  • Adequate BM function defined as:
  • Hemoglobin \>5.6 mmol/l or Hb \> 9 g/dL, unless low Hb is directly attributable to CLL infiltration of the BM, proven by BM biopsy;
  • Absolute neutrophil count (ANC) \>1.0 x 109/L (1,000/μL), unless low ANC is directly attributable to CLL infiltration of the BM, proven by BM biopsy;
  • Platelet count \>30 x 109/L (30,000/μL), unless low platelets is directly attributable to CLL infiltration in the BM;
  • Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl) ≥ 50ml/min (Cockcroft-Gault appendix F);
  • Adequate liver function as indicated:
  • Serum aspartate transaminase (ASAT) and alanine transaminase (ALAT) ≤ 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; unless receiving anticoagulation;
  • Negative serological testing for hepatitis B virus (HBV) (Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) negative) and hepatitis C virus (hepatitis C antibody). Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative PCR within 6 weeks before enrollment. Those who are PCR positive will be excluded; Please note: For patients positive for anti-HBc, HBV-DNA PCR has to be repeated every month until 12 months after last dose of study treatment.
  • +3 more criteria

You may not qualify if:

  • Active CLL/SLL directed therapy within the last 14 days;
  • Prior treatment with a CD3 × CD20 bispecific antibody or CAR T-cell therapy
  • Transformation of CLL (Richter's transformation);
  • Prior allogeneic stem cell transplantation and/or solid organ transplantation;
  • Patient with a history of confirmed progressive multifocal leukoencephalopathy (PML);
  • Malignancies other than CLL currently requiring systemic therapy or not treated in curative intention or showing signs of progression after curative treatment;
  • Known allergy to xanthine oxidase inhibitors and/or rasburicase;
  • History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components);
  • Active bleeding or uncontrolled severe bleeding diathesis (e.g., hemophilia or severe von Willebrand disease);
  • Active fungal, bacterial, and/or viral infection CTCAEgrade \> 1; Please note: active controlled as well as chronic/recurrent infections are at risk of reactivation/infection during treatment;
  • 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 HIV-positive;
  • Patient requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor/inducer (see appendix J) or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists;
  • CTCAE grade III-IV cardiovascular disease including but not limited to:
  • Unstable or uncontrolled disease/condition related to or affecting cardiac function, eg, unstable angina, congestive heart failure grade III or IV as classified by the New York Heart Association (see appendix E), uncontrolled clinically significant cardiac arrhythmia (CTCAE grade II or higher), or clinically significant electrocardiogram (ECG) abnormalities.
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

BE-Antwerpen-ZNASTUIVENBERG

Antwerp, Belgium

NOT YET RECRUITING

BE-Roeselare-AZDELTA

Roeselare, Belgium

NOT YET RECRUITING

DK-Aalborg-ALBOGUH

Aalborg, Denmark

NOT YET RECRUITING

DK-Copenhagen-RIGSHOSPITALET

Copenhagen, Denmark

RECRUITING

DK-Odense-OUH

Odense, Denmark

NOT YET RECRUITING

DE-Berlin-HELIOSBERLINBUCH

Berlin, Germany

NOT YET RECRUITING

DE-Köln-UKKOELN

Cologne, Germany

NOT YET RECRUITING

DE-Freiburg-UNIKLINIKFREIBURG

Freiburg im Breisgau, Germany

NOT YET RECRUITING

DE-Greifswald-UNIGREIFSWALD

Greifswald, Germany

NOT YET RECRUITING

DE-Munster-GEMEINSCHAFTSPRAXIS

Münster, Germany

NOT YET RECRUITING

DE-Stuttgart-RBK

Stuttgart, Germany

NOT YET RECRUITING

DE-Ulm-UNIKLINKULM

Ulm, Germany

NOT YET RECRUITING

NL-Den Bosch-JBZ

's-Hertogenbosch, Netherlands

NOT YET RECRUITING

NL-Alkmaar-NWZ

Alkmaar, Netherlands

NOT YET RECRUITING

NL-Amersfoort-MEANDERMC

Amersfoort, Netherlands

NOT YET RECRUITING

NL-Amsterdam-AMC

Amsterdam, Netherlands

NOT YET RECRUITING

NL-Dordrecht-ASZ

Dordrecht, Netherlands

NOT YET RECRUITING

NL-Ede-ZGV

Ede, Netherlands

NOT YET RECRUITING

NL-Eindhoven-CATHARINA

Eindhoven, Netherlands

NOT YET RECRUITING

NL-Groningen-UMCG

Groningen, Netherlands

NOT YET RECRUITING

NL-Leeuwarden-MCL

Leeuwarden, Netherlands

NOT YET RECRUITING

NL-Den Haag-HAGA

The Hague, Netherlands

NOT YET RECRUITING

NL-Tilburg-ETZ

Tilburg, Netherlands

NOT YET RECRUITING

NL-Utrecht-UMCUTRECHT

Utrecht, Netherlands

NOT YET RECRUITING

Related Links

MeSH Terms

Interventions

venetoclax

Central Study Contacts

Arnon Kater

CONTACT

+31 6-11491753a.p.kater@amsterdamumc.nl

Mark-David Levin

CONTACT

m-d.levin@asz.nl

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 1, 2023

First Posted

March 30, 2023

Study Start

April 10, 2024

Primary Completion (Estimated)

March 1, 2029

Study Completion (Estimated)

November 1, 2032

Last Updated

April 12, 2024

Record last verified: 2024-04

Locations

BE(2)DK(3)NL(12)DE(7)