JOURNAL ONKOLOGIE – STUDIE
Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia
Rekrutierend
NCT-Nummer:
NCT04623541
Studienbeginn:
November 2020
Letztes Update:
06.01.2021
Wirkstoff:
Epcoritamab
Indikation (Clinical Trials):
Leukemia, Leukemia, Lymphoid, Leukemia, Lymphocytic, Chronic, B-Cell
Geschlecht:
Alle
Altersgruppe:
Erwachsene (18+)
Phase:
-
Sponsor:
Genmab
Collaborator:
AbbVie
Kontakt
Kontakt:
Phone: +4570202728
E-Mail: clinicaltrials@genmab.com» Kontaktdaten anzeigen
Studienlocations (3 von 10)
University of Cologne
Köln
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-MapsHackensack Meridian Hospital
07601 Hackensack
United StatesNoch nicht rekrutierend» Google-MapsFred Hutchinson Cancer Research Center
98109 Seattle
United StatesNoch nicht rekrutierend» Google-Maps
Köln
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-MapsHackensack Meridian Hospital
07601 Hackensack
United StatesNoch nicht rekrutierend» Google-MapsFred Hutchinson Cancer Research Center
98109 Seattle
United StatesNoch nicht rekrutierend» Google-Maps
UZ Leuven
Leuven
BelgiumNoch nicht rekrutierend» Google-MapsRigshospitalet
2100 København
DenmarkNoch nicht rekrutierend» Google-MapsOdense University Hospital
5000 Odense
DenmarkRekrutierend» Google-MapsÅrhus University Hospital
8000 Århus
DenmarkRekrutierend» Google-MapsAmsterdam UMC
Amsterdam
NetherlandsRekrutierend» Google-MapsUniversitair Medisch Centrum Groningen
9713 Groningen
NetherlandsNoch nicht rekrutierend» Google-MapsMaastricht University Medical Center
6229 Maastricht
NetherlandsNoch nicht rekrutierend» Google-Maps
Alle anzeigen Leuven
BelgiumNoch nicht rekrutierend» Google-MapsRigshospitalet
2100 København
DenmarkNoch nicht rekrutierend» Google-MapsOdense University Hospital
5000 Odense
DenmarkRekrutierend» Google-MapsÅrhus University Hospital
8000 Århus
DenmarkRekrutierend» Google-MapsAmsterdam UMC
Amsterdam
NetherlandsRekrutierend» Google-MapsUniversitair Medisch Centrum Groningen
9713 Groningen
NetherlandsNoch nicht rekrutierend» Google-MapsMaastricht University Medical Center
6229 Maastricht
NetherlandsNoch nicht rekrutierend» Google-Maps
Studien-Informationen
Detailed Description:The purpose of the escalation part of the trial is to determine the recommended phase 2 dose
(RP2D) and the maximum tolerated dose (if reached) as well as establish the safety profile of
epcoritamab in patients with R/R CLL.
In the expansion part additional patients will be treated with epcoritamab at the RP2D and
the the purpose is to assess and evaluate the preliminary efficacy, safety and tolerability
profiles of epcoritamab at the RP2D.
Ein-/Ausschlusskriterien
Inclusion Criteria1. Subject must sign an ICF, prior to any screening procedures.
2. Must have active CLL disease that needs treatment per iwCLL2018
3. R/R CLL after receiving at least 2 prior lines of systemic antineoplastic therapy,
including treatment with (or intolerance of) a BTK inhibitor
4. Has Measurable Disease with ≥5 × 109/L (5,000/μL) B lymphocytes in peripheral blood or
Presence of measurable lymphadenopathy and/or organomegaly
5. ECOG performance status score of 0 or 1
6. Screening flow cytometry evidence of CD20 positivity
7. Has laboratory parameters as follows:
a. HBG-≥9.0 g/dL; ANC-≥1.0 x 109/L; Platelets-≥30 x 109/L
8. Received a cumulative dose of corticosteroids less than the equivalent of 250 mg of
prednisone within the 2-week period before the first dose
9. Availability of fresh bone marrow material
10. Must take prophylaxis for TLS
11. A woman must be either not of childbearing potential or of childbearing potential and
practicing a highly effective method of birth control, and must have a negative serum
beta-human chorionic gonadotropin (beta-hCG) and urine pregnancy test at screening.
12. A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control.
Exclusion Criteria
1. Transformation of CLL to aggressive non-Hodgkin lymphoma
2. Received prior treatment with a CD3 × CD20 bispecific antibody.
3. Received any prior allogeneic HSCT or solid organ transplantation.
4. Received treatment with an anti-cancer biologic including anti-CD20 therapy,
radio-conjugated or toxin-conjugated antibody or CAR T-cell therapy or investigational
drug or medical device within 4 weeks, before the first dose.
5. Received chemotherapy or radiation therapy within 2 weeks of the first dose of
epcoritamab.
6. Has autoimmune disease or other diseases that require permanent or high-dose
immunosuppressive therapy.
7. Has uncontrolled intercurrent illness.
8. Toxicities from previous anti-cancer therapies have not resolved to baseline levels or
to Grade 1 or less except for alopecia and peripheral neuropathy.
9. Primary central nervous system (CNS) lymphoma or known CNS involvement at screening.
10. Known past or current malignancy other than inclusion diagnosis
11. Subject has suspected allergies, hypersensitivity, or intolerance to epcoritamab or
its excipients.
12. Subject is unable to tolerate uric acid reducing medications
13. Has had major surgery within 3 weeks before screening or will not have fully recovered
from surgery, or has major surgery planned during the time the subject is expected to
participate in the trial (or within 4 weeks after the last dose of epcoritamab).Known
history/positive serology for hepatitis B.
14. Known medical history or ongoing hepatitis C infection that has not been cured.
15. HIV tested positive at screening.
16. Is a woman who is pregnant or breast-feeding, or who is planning to become pregnant
while enrolled in this trial or within 12 months after the last dose of epicoritamab.
17. Is a man who plans to father a child while enrolled in this trial or within 12 months
after the last dose of epicoritamab.
Studien-Rationale
Primary outcome:1. Dose escalation part: Incidence of dose limiting toxicities (DLTs) (Time Frame - For each subject in a given dose escalation cohort, DLTs are assessed during the first cycle (28 days).):
To identify the recommended phase II dose (RP2D)
2. Dose escalation part: Incidence of dose limiting toxicities (DLTs) (Time Frame - For each subject in a given dose escalation cohort, DLTs are assessed during the first cycle (28 days).):
To identify maximum tolerated dose (MTD) if reached
3. Dose expansion part: assess preliminary efficacy of epcoritamab (Time Frame - response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose)):
overall response rate
4. Dose escalation and expansion part: Adverse events (AEs) (Time Frame - AEs are collected throughout trial until the end of the safety follow-up period (60 days after last dose)):
To assess the safety and tolerability of epcoritamab throughout the treatment period of patients participating in the trial)
Secondary outcome:
1. Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
Pharmacokinetic (PK) parameters Clearance (Cl)
2. Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
PK parameters Volume of Distrubution (Vd)
3. Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
PK parameters maximum (peak) plasma drug concentration (Cmax)
4. Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
PK parameters time to reach maximum (peak) plasma concentration (Tmax)
5. Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
PK parameters Area under the concentration-time curve (AUC) from time zero to last quantifiable sample
6. Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
PK parameters Area under the concentration-time curve (AUC) from time zero to infinity
7. Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
PK parameters pre-dose (trough) concentrations
8. Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
PK parameters elimination half-life (T1/2)
9. Dose escalation and expansion part: To evaluate pharmacodynamic markers of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
pharmacodynamic (PD) marker cytokines
10. Dose escalation and expansion part: To evaluate pharmacodynamic markers of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
pharmacodynamic (PD) marker immune subset CD4
11. Dose escalation and expansion part: To evaluate pharmacodynamic markers of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
pharmacodynamic (PD) marker immune subset CD8
12. Dose escalation and expansion part: To evaluate pharmacodynamic markers of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
pharmacodynamic (PD) marker immune subset B cells
13. Dose escalation and expansion part: To evaluate pharmacodynamic markers of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
pharmacodynamic (PD) marker immune subset activation marker positive/expression level
14. Dose escalation and expansion part: Evaluate the immunogenicity of epcoritamab (Time Frame - assessed through trial until the end of the treatment period, expected average of 1 year):
incidence of antidrug-antibodies to epcoritamab
15. Dose escalation part: Assess the preliminary anti-tumor activity of epcoritamab (Time Frame - response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose)):
overall response rate
16. Dose escalation and expansion part: Assess the preliminary anti-tumor activity of epcoritamab (Time Frame - response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose)):
duration of response
17. Dose escalation and expansion part: Assess the preliminary anti-tumor activity of epcoritamab (Time Frame - response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose)):
time to response
18. Dose escalation and expansion part: Assess the preliminary anti-tumor activity of epcoritamab (Time Frame - response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose)):
progression free survival
19. Dose escalation and expansion part: Assess the preliminary anti-tumor activity of epcoritamab (Time Frame - response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose)):
overall survival
Geprüfte Regime
- Epcoritamab (GEN3013; DuoBody®-CD3xCD20):
Epcoritamab will be administered in cycles of 28 days.
Quelle: ClinicalTrials.gov
