Trial Title:
CAR-T-cell Treatment for Untreated High Risk MANtle Cell Lymphoma
NCT ID:
NCT06482684
Condition:
Mantle Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Mantle-Cell
Brexucabtagene autoleucel
Ibrutinib
Conditions: Keywords:
High Risk MCL
CAR-T-Cells
MCL Firstline Treatment
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
KTE-X19
Description:
See description of treatment arms
Arm group label:
Arm A
Intervention type:
Drug
Intervention name:
Ibrutinib
Description:
See description of treatment arms
Arm group label:
Arm A
Arm group label:
Arm B
Summary:
First-line CAR-T-cell consolidation after an abbreviated induction with 2 cycles of
Rituximab and Ibrutinib prior to CAR-T-cell treatment and followed by 6 months of
maintenance with Ibrutinib in patients with high risk MCL.
Detailed description:
This phase II clinical trial will compare the efficacy, safety and tolerability of
first-line treatment with KTE-X19 after a shortened induction with Rituximab and
Ibrutinib to conventional immunochemotherapy and Ibrutinib followed by ASCT in younger
patients in high-risk MCL patients or immunochemotherapy plus BTKi for elderly, but still
fit patients (need to be CAR-T-cell eligible). As primarily the potential of CAR-T-cell
treatment is evaluated within this trial, in case of failure to achieve a partial
response will be treated with 2 additional cycles of R-CHOP, which can be omitted in case
of sufficient response to Ibrutinib-based treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically confirmed diagnosis of MCL according to WHO classification, with
documentation of either overexpression of cyclin D1 or presence of t(11;14)
2. At least one High Risk MCL - feature as defined as I. MIPI-c high intermediate (HI)
or high (H) risk (i.e. high risk MIPI irrespective of Ki-67 or intermediate risk
MIPI and Ki-67>=30% (Ki-67 based on local pathology) and/or II. TP53-mutation and/or
TP53-overexpression by immunohistochemistry (> 50% of lymphoma cells)
3. No prior treatment for MCL
4. Stage II-IV (Ann Arbor)
5. 18-75 years
6. At least 1 measurable lesion according to the Lugano Response Criteria (>1.5 cm
nodal lesion or > 1cm extranodal lesion); in case of bone marrow infiltration only,
bone marrow aspiration and biopsy is mandatory for all staging evaluations.
7. ECOG performance status ≤ 2
8. The following laboratory values at screening (unless discrepancies are related to
MCL):
I. Absolute neutrophil count (ANC) ≥ 1000 cells/μL II. Platelets ≥75,000 cells/μL
III. Creatinine <2 mg/dL or calculated creatinine clearance ≥60 mL/min IV.
Transaminases (AST and ALT) < 2.5 x ULN V. Total bilirubin <= 2 x ULN unless other
reason known (e.g. Gilbert-Meulengracht-Syndrome, or due to lymphoma involvement)
9. No evidence of CNS-disease
10. Written informed consent form according to ICH/EU GCP and national regulations,
ability to follow study instructions and likely to attend and complete all required
visits
11. Sexually active men and women of child-bearing potential must agree to use one of
the highly effective contraceptive methods (combined oral contraceptives using two
hormones, contraceptive implants, injectables, intrauterine devices, sterilized
partner) together with one of the barrier methods (latex condoms, diaphragms,
contraceptive caps) while on study; this should be maintained for 6 months after the
last dose of KTE-X19 or for 3 months after last dose of Ibrutinib, whichever is
longer
12. Negative serum or urine pregnancy test (Females of childbearing potential only,
Females who have undergone surgical sterilization or who have been postmenopausal
for at least 2 years are not considered to be of childbearing potential)
13. Willingness not to drive a motor vehicle for 8 weeks post CAR T cell treatment
14. Possibility to reach the site within 2 hours in case of toxicity / emergency
Exclusion Criteria:
1. Subjects not able to give consent
2. Subjects without legal capacity, unable to understand the nature, scope,
significance and consequences of this clinical study
3. Known history of hypersensitivity to the investigational drug, to drugs with a
similar chemical structure or to aminoglycosides
4. Simultaneously active participation in another clinical study involving an
investigational medicinal product within 30 days prior to enrollment. Patients
included in follow up periods of other clinical trials without ongoing trial
medication are allowed
5. Subjects with a physical or psychiatric condition which at the investigator's
discretion may put the subject at risk, may confound the study results, or may
interfere with the subject's participation in this clinical study
6. Known or persistent abuse of medication, drugs or alcohol
7. Serious concomitant disease interfering with a regular therapy according to the
study protocol:
I. Clinically significant cardiovascular disease such as symptomatic arrhythmias,
congestive heart failure, higher grade AV-block, unstable angina, myocardial
infarction, cardiac angioplasty or stenting within 12 months of Screening, or any
Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York
Heart Association Functional Classification or LVEF below 50% II. Baseline oxygen
saturation ≤ 92% on room air III. Clinical significant pleural effusion (if not
lymphoma related) IV. Endocrinological (severe, not sufficiently controlled diabetes
mellitus)
8. Current or planned pregnancy or nursing women. History of or active malignancy other
than MCL, non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast)
or prostate cancer unless disease-free for at least 3 years (and PSA within normal
range in case of prostate cancer).
9. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or
requiring intravenous (IV) antimicrobials for management.
10. Positive test results for chronic HBV infection (defined as positive HBsAg serology)
(mandatory testing) Patients with occult or prior HBV infection (defined as negative
HBsAg and positive total HBcAb) may be included if HBV DNA is undetectable
11. Positive test results for hepatitis C (mandatory hepatitis C virus [HCV] antibody
serology testing). Patients positive for HCV antibody are eligible only if PCR is
negative for HCV RNA
12. Patients with known HIV infection (mandatory test)
13. History or presence of CNS disorder, such as seizure disorder, cerebrovascular
ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior
reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement
14. History of or active autoimmune disease (e.g. Crohn's disease, rheumatoid arthritis,
systemic lupus) resulting in end organ injury or requiring systemic
immunosuppression / systemic medication within the last 2 years
15. History of deep vein thrombosis or pulmonary embolism requiring therapeutic
anticoagulation within 6 months of enrolment
16. Known severe primary immunodeficiency
17. Any medical condition likely to interfere with assessment of safety or efficacy of
study treatment
18. Live vaccine ≤ 6 weeks prior to planned start of study treatment
19. Any psychological, familial, sociological, or geographical condition potentially
hampering compliance with the study protocol and follow up schedule
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University Hospital of Mainz
Address:
City:
Mainz
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Georg Hess, MD
Phone:
+49 6131 175040
Email:
georg.hess@unimedizin-mainz.de
Facility:
Name:
Klinikum der Universität München
Address:
City:
Munich
Zip:
81377
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Christian Schmidt, MD
Phone:
+49 (0)89 4400-77907
Contact backup:
Last name:
Christian Schmidt, MD
Phone:
+49 (0)89 4400-77907
Email:
Christian_Schmidt@med.uni-muenchen.de
Investigator:
Last name:
Christian Schmidt, MD
Email:
Principal Investigator
Investigator:
Last name:
Martin Dreyling, MD
Email:
Sub-Investigator
Investigator:
Last name:
Marion Subklewe, MD
Email:
Sub-Investigator
Start date:
February 15, 2024
Completion date:
December 31, 2031
Lead sponsor:
Agency:
Christian Schmidt, MD
Agency class:
Other
Collaborator:
Agency:
Johannes Gutenberg University Mainz
Agency class:
Other
Source:
Ludwig-Maximilians - University of Munich
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06482684
