Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Authorised, recruiting
Participants planned
150
Countries
5
Sites
43
Mantle Cell Lymphoma (MCL)
Exploratively compare the efficacy of the experimental CAR-T-cell treatment (Arm A) with standard of care (Arm B) in terms of the primary endpoint
Key facts
- Sponsor
- Klinikum Der Universitat Munchen AöR
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 8 Apr 2024 → ongoing
- Decision date (initial)
- 2024-08-30
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Kite Pharma, Inc. · Janssen Pharmaceutica
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Therapy, Efficacy
Exploratively compare the efficacy of the experimental CAR-T-cell treatment (Arm A) with standard of care (Arm B) in terms of the primary endpoint
Secondary objectives 1
- To further assess the efficacy, safety, and tolerability of the experimental CAR T-cell treatment (Arm A) compared to standard of care (Arm B) using secondary and exploratory endpoints
Conditions and MedDRA coding
Mantle Cell Lymphoma (MCL)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | PT | 10026803 | Mantle cell lymphoma stage II | 100000004864 |
| 21.0 | PT | 10026804 | Mantle cell lymphoma stage III | 100000004864 |
| 21.0 | PT | 10026805 | Mantle cell lymphoma stage IV | 100000004864 |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2022-502405-15-00 | Early treatment intensification in patients with high risk Mantle Cell Lymphoma using CAR-T-cell treatment after an abbreviated induction therapy with Rituximab and Ibrutinib and 6 months Ibrutinib maintenance (Arm A) as compared to standard of care induction and maintenance (Arm B) | Klinikum Der Universitat Munchen AöR |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 14
- Histologically confirmed diagnosis of MCL according to WHO classification, with documentation of either overexpression of cyclin D1 or presence of t(11;14)
- 18-75 years
- 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.
- ECOG performance status ≤ 2
- The following laboratory values at screening (unless related to MCL): I. Absolute neutrophil count (ANC) ≥ 1000 cells/μLII. 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)
- No evidence of CNS-disease
- 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
- 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 12 months after the last dose of brexu-cel or for 3 months after last dose of Ibrutinib, whichever is longer
- 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)
- Willingness not to drive a motor vehicle for 8 weeks post CAR T cell treatment
- Possibility to reach the site within 2 hours in case of toxicity / emergency
- At least one high-risk MCL – feature 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 deletion and /or mutation and/or TP53 overexpression by immunohistochemistry (> 50% of lymphoma cells), sequencing (mutations and deletions) and FISH
- No prior systemic treatment for MCL, except pre-phase treatment as outlined in this trial protocol
- Stage II-IV (according to Lugano 2014 criteria)
Exclusion criteria 20
- Subjects not able to give consent
- Positive test results for chronic HBV infection (defined as positive HBsAg serology, mandatory testing) Note: patients with occult or prior HBV infection (defined as negative HBs-Ag and positive total antiHBc-Ab) may be included if HBV DNA is undetectable and patient can receive antiviral prophylaxis.
- Positive test results for hepatitis C (mandatory hepatitis C virus [HCV] antibody serology testing). Patients positive for anti-HCV antibody are eligible only if PCR is negative for HCV RNA
- Patients with known HIV infection (mandatory test)
- 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
- History of or active autoimmune disease (e.g. Crohn’s disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immuno-suppression / systemic medication within the last 2 years
- History of deep vein thrombosis or pulmonary embolism requiring therapeutic anticoagulation within 6 months of enrollment
- Known severe primary immunodeficiency
- Any medical condition likely to interfere with safety or efficacy of study treatment
- Live vaccine ≤ 6 weeks prior to planned start of study treatment
- Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow up schedule
- Subjects without legal capacity, unable to understand the nature, scope, significance and consequences of this clinical study
- Known history of hypersensitivity to the investigational drug, to drugs with a similar chemical structure or to aminoglycosides
- Simultaneously active participation in another clinical study involving an investigational medicinal product within 30 days prior to enrollment. Patients included infollow up periods of other clinical trials without ongoing trial medication are allowed
- 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
- Known or persistent abuse of medication, drugs or alcohol
- Serious concomitant disease interfering with a regular therapy according to the study protocol: I. Clinically symptomatic cardiovascular disease such as 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. Endocrinological, e.g. severe, not sufficiently controlled diabetes mellitus
- 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).
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management.
- History of or active malignancy other than MCL unless disease-free for at least 3 years, except nonmelanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, breast) or treated prostate cancer with PSA within normal range.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Primary endpoint: Failure-free survival (FFS) from randomization. Failure events are defined as the earliest of the following: o Stable disease at the end of induction (Arm B, or Arm A if CAR-T-cells are not infused) or within 12 weeks from CAR-T-cell infusion (Arm A), o Progressive disease at or at any time after end of induction treatment, and o Death from any cause at any time
Secondary endpoints 8
- Progression-free survival (PFS) from randomization
- Complete remission (CR) rate and overall response rate (ORR: CR, PR) approx. 6.5 months from randomization
- Rate of PET negative CR (complete metabolic response rate, per Lugano criteria) approx. 6.5 months from randomization
- PFS in responders approx. 6.5 months from randomization (landmark analysis)
- Best response within 2 years from randomization
- Time to best response and time to first response from randomization
- Overall survival (OS) from randomization
- Safety: adverse events, serious adverse events, graded according to CTCAE
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
IMBRUVICA 140 mg hard capsules
PRD1729393 · Product
- Active substance
- Ibrutinib
- Substance synonyms
- 1-((3R)-3-(4-AMINO-3-(4-PHENOXYPHENYL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-1-YL)PIPERIDIN-1- YL)PROP-2-EN-1-ONE
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 560 mg milligram(s)
- Max total dose
- 504000 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01EL01 — -
- Marketing authorisation
- EU/1/14/945/002
- MA holder
- JANSSEN-CILAG INTERNATIONAL NV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Labelling for study
Tecartus 0.4 - 2 x 10e8 cells dispersion for infusion
PRD9251158 · Product
- Active substance
- Brexucabtagene Autoleucel
- Substance synonyms
- Autologous peripheral blood T cells CD4 and CD8 selected and CD3 and CD28 activated transduced with retroviral vector expressing anti-CD19 CD28/CD3-zeta chimeric antigen receptor and cultured, KTE-X19
- Pharmaceutical form
- DISPERSION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 20 million organisms million organisms
- Max total dose
- 20 million organisms million organisms
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- NOTASSIGN — -
- Marketing authorisation
- EU/1/20/1492/001
- MA holder
- KITE PHARMA EU B.V.
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EMA/OD/0000013608
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Labelling for study
Auxiliary 18
SUB06859MIG · Substance
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION OR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 750 mg/m2 milligram(s)/sq. meter
- Max total dose
- 4500 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB09490MIG · Substance
- Active substance
- Oxaliplatin
- Pharmaceutical form
- INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 130 mg/m2 milligram(s)/sq. meter
- Max total dose
- 390 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB16451MIG · Substance
- Active substance
- Pegfilgrastim
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 6 mg milligram(s)
- Max total dose
- 36 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07627MIG · Substance
- Active substance
- Filgrastim
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 10 µg/Kg microgram(s)/kilogram
- Max total dose
- 740 µg/Kg microgram(s)/kilogram
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB05101MIG · Substance
- Active substance
- Vincristine Sulfate
- Pharmaceutical form
- INJECTION
- Route of administration
- IV INFUSION
- Max daily dose
- 2 mg milligram(s)
- Max total dose
- 12 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07678MIG · Substance
- Active substance
- Fludarabine
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 30 mg/m2 milligram(s)/sq. meter
- Max total dose
- 90 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB05707MIG · Substance
- Active substance
- Bendamustine
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 90 mg/m2 milligram(s)/sq. meter
- Max total dose
- 1080 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06880MIG · Substance
- Active substance
- Cytarabine
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 4000 mg/m2 milligram(s)/sq. meter
- Max total dose
- 18000 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08728MIG · Substance
- Active substance
- Melphalan
- Pharmaceutical form
- POWDER AND SOLVENT FOR SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 140 mg/m2 milligram(s)/sq. meter
- Max total dose
- 140 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06391MIG · Substance
- Active substance
- Doxorubicin
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- IV INFUSION
- Max daily dose
- 50 mg/m2 milligram(s)/sq. meter
- Max total dose
- 300 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07483MIG · Substance
- Active substance
- Cisplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 100 mg/m2 milligram(s)/sq. meter
- Max total dose
- 300 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06132MIG · Substance
- Active substance
- Carmustine
- Pharmaceutical form
- POWDER AND SOLVENT FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 300 mg/m2 milligram(s)/sq. meter
- Max total dose
- 300 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB20313 · Substance
- Active substance
- Tocilizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 800 mg milligram(s)
- Max total dose
- 3200 mg milligram(s)
- Max treatment duration
- 1 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07017MIG · Substance
- Active substance
- Dexamethasone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL AND IV
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 480 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10018MIG · Substance
- Active substance
- Prednisolone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL AND IV
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 3000 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB12570MIG · Substance
- Active substance
- Rituximab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 375 mg/m2 milligram(s)/square meter
- Max total dose
- 9000 mg/m2 milligram(s)/square meter
- Max treatment duration
- 42 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07337MIG · Substance
- Active substance
- Etoposide
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 200 mg/m2 milligram(s)/sq. meter
- Max total dose
- 800 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10985MIG · Substance
- Active substance
- Thiotepa
- Pharmaceutical form
- POWDER FOR CONCENTRATE FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 10 mg/kg milligram(s)/kilogram
- Max total dose
- 10 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Klinikum Der Universitat Munchen AöR
- Sponsor organisation
- Klinikum Der Universitat Munchen AöR
- Address
- Marchioninistraße 15, Hadern Hadern
- City
- Munich
- Postcode
- 81377
- Country
- Germany
Scientific contact point
- Organisation
- Klinikum Der Universitat Munchen AöR
- Contact name
- Martin Dreyling
Public contact point
- Organisation
- Klinikum Der Universitat Munchen AöR
- Contact name
- Martin Dreyling
Third parties 2
| Organisation | City, country | Duties |
|---|---|---|
| Proinnovera GmbH ORG-100010249
|
Muenster, Germany | On site monitoring, Code 12, Code 5 |
| Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR ORG-100008474
|
Mainz, Germany | Code 13 |
Locations
5 EU/EEA countries · 43 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Czechia | Ongoing, recruiting | 7 | 2 |
| France | Ongoing, recruiting | 42 | 12 |
| Germany | Ongoing, recruiting | 64 | 18 |
| Netherlands | Authorised, recruiting | 10 | 3 |
| Spain | Ongoing, recruiting | 27 | 8 |
| Rest of world | — | 0 | — |
Investigational sites
Vseobecna Fakultni Nemocnice V Praze
I. interní klinika - klinika hematologie, U Nemocnice 499/2, Nove Mesto, Prague 2
Fakultni Nemocnice Brno
Interní hematologická a onkologická klinika, Jihlavska 340/20, Bohunice, Brno
Assistance Publique Hopitaux De Paris
Hematology, 1 Avenue Claude Vellefaux, 75010, Paris
Centre Hospitalier Universitaire De Lille
Hematology, Rue Michel Polonowski, 59000, Lille
Assistance Publique Hopitaux De Paris
Hematology, 149 Rue De Sevres, 75015, Paris
Hospices Civils De Lyon
Hematology, 165 Chemin Du Grand Revoyet, 69310, Pierre Benite
Centre Hospitalier Universitaire De Bordeaux
Hematology, Avenue De Magellan, 33600, Pessac
Centre Hospitalier Universitaire De Nantes
Hematology, 1 Place Alexis Ricordeau, 44000, Nantes
Centre Hospitalier Universitaire De Montpellier
Hematology, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5
Centre Hospitalier Universitaire De Dijon
Hematology, 14 Rue Paul Gaffarel, 21000, Dijon
Centre Hospitalier Universitaire De Rennes
Hematology, 2 Rue Henri Le Guilloux, 35000, Rennes
Assistance Publique Hopitaux De Paris
Hematology, 51 Avenue Du Mal De Lattre De Tassigny, 94010, Creteil Cedex
Institut Paoli Calmettes
Hematology, 232 Boulevard De Sainte Marguerite, Bp 156, Marseille
University Hospital Of Clermont-Ferrand
Hematology, 1 Place Lucie Et Raymond Aubrac, 63100, Clermont-Ferrand
Klinikum der Universitaet Muenchen AöR
Med. Klinik und Poliklinik III, Marchioninistrasse 15, Hadern, Munich
Universitaetsklinikum Essen AöR
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum, Hufelandstrasse 55, Holsterhausen, Essen
Universitaetsklinikum Schleswig-Holstein
Klinik für Innere Medizin II, Arnold-Heller-Strasse 3, Brunswik, Kiel
Westfaelische Wilhelms-Universitaet Muenster
Medizinische Klinik A; KMT Zentrum, Gebaeude A1, Albert-Schweitzer-Campus 1, Muenster
Universitaetsklinikum Duesseldorf AöR
Klinik für Hämatologie, Onkologie und klinische Immunologie, Moorenstrasse 5, Bilk, Duesseldorf
Universitaetsmedizin Goettingen
Zentrum Innere Medizin, Klinik für Hämatologie und Medizinische Onkologie, Robert-Koch-Strasse 40, Weende, Goettingen
Universitaetsklinikum Ulm AöR
Klinik für Innere Medizin III, Albert-Einstein-Allee 23, Eselsberg, Ulm
Universitaet Des Saarlandes
Hematology/Oncology, Kirrberger Strasse 100, 66421, Homburg
Universitaetsklinikum Wuerzburg AöR
Med. Klinik und Poliklinik II / ZIM, Oberduerrbacher Strasse 6, Grombuehl, Wuerzburg
University Hospital Cologne AöR
Klinik I für Innere Medizin, Kerpener Strasse 62, Lindenthal, Cologne
Charite Universitaetsmedizin Berlin KöR
Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie, Hindenburgdamm 30, Lichterfelde, Berlin
Helios Klinikum Berlin-Buch GmbH
Hämatologie, Onkologie und Tumorimmunologie, Schwanebecker Chaussee 50, Buch, Berlin
University Medical Center Hamburg-Eppendorf
Klinik und Poliklinik für Stammzelltransplantation, Martinistrasse 52, Eppendorf, Hamburg
Goethe University Frankfurt
Medizinische Klinik 2 Hämatologie und Medizinische Onkologie, Theodor-Stern-Kai 7, 60590, Frankfurt Am Main
Universitaet Leipzig
Med.-Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie, Liebigstrasse 20, Zentrum-Suedost, Leipzig
Medical Center - University Of Freiburg
Klinik für Innere Medizin I, Schwerpunkt Hämatologie, Onkologie und Stammzelltransplantation, Hugstetter Strasse 55, Stuehlinger, Freiburg Im Breisgau
Universitaetsmedizin Der Johannes Gutenberg-Universitaet Mainz Koerperschaft Des Offentlichen Rechts
III. Medizinische Klinik und Poliklinik, Building 704, Langenbeckstrasse 1, Mainz
Universitaetsklinikum Heidelberg AöR
Med. Klinik V - Hämatologie/Onkologie und Rheumatologie, Im Neuenheimer Feld 410, Neuenheim, Heidelberg
Stichting Amsterdam UMC
Hematology, De Boelelaan 1117, 1081 HV, Amsterdam
Universitair Medisch Centrum Groningen
Hematology, Hanzeplein 1, 9713 GZ, Groningen
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Hematology, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Hospital Universitario De Salamanca
Hematology, Paseo De San Vicente 58-182, 37007, Salamanca
University Hospital Virgen Del Rocio S.L.
Hematology and hemotherapy, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Clinic De Barcelona
Hematology, Calle Villarroel 170, 08036, Barcelona
Hospital General Universitario Gregorio Maranon
Hematology and hemotherapy service. Bone marrow transplant unit., Calle Del Doctor Esquerdo 46, 28009, Madrid
Institut Catala D'oncologia
Hematology, Avinguda De La Gran Via De L'hospitalet 199-203, 08908, L'hospitalet De Llobregat
Hospital Universitario 12 De Octubre
Hematology and hemotherapy, Bloque D, Avenida De Cordoba Sn, Madrid
Hospital Universitario Y Politecnico La Fe
Hematology, Avenida De Fernando Abril Martorell 106, 46026, Valencia
Hospital Universitari Vall D Hebron
Hematology, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Czechia | 2025-01-24 | 2025-01-24 | |||
| France | 2025-04-16 | 2025-04-16 | |||
| Germany | 2024-04-08 | 2024-04-08 | |||
| Netherlands | 2026-02-02 | ||||
| Spain | 2024-12-10 | 2024-12-11 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 81 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_CARMAN_Protocol_FP_ | 2.3 |
| Protocol (for publication) | D3_ DSMB Charter_CARMAN_FP | 1.0 |
| Protocol (for publication) | D4 NHL-HG29 Spanish | N/A |
| Protocol (for publication) | D4_CARMAN Patient Diary ARM B older 65 DE | 1 |
| Protocol (for publication) | D4_CARMAN Patient Card DE | 1 |
| Protocol (for publication) | D4_CARMAN Patient Diary ARM A NL | 1 |
| Protocol (for publication) | D4_CARMAN Patient Diary ARM B younger 65 DE | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Card_FR | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary Arm A DE | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM A Czech | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM A FR | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM A Spanish | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM A_Czech_FP | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM A_FP | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_Czech_FP | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_older 65 Czech | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_older 65 FR | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_older 65 Spanish | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_older 65_Czech_FP | 1.0 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_older 65_FP | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_older 65_NL | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_younger 65 Czech | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_younger 65 FR | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_younger 65 NL | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_younger 65 Spanish | 1 |
| Protocol (for publication) | D4_CARMAN_Patient Diary_ARM B_younger 65_FP | 1 |
| Protocol (for publication) | D4_NHL-HG29 Czech | N/A |
| Protocol (for publication) | D4_NHL-HG29 Dutch | N/A |
| Protocol (for publication) | D4_NHL-HG29 English_FP | 1 |
| Protocol (for publication) | D4_NHL-HG29 French | N/A |
| Protocol (for publication) | D4_NHL-HG29 German | N/A |
| Protocol (for publication) | D4_Patient card Czech | 1 |
| Protocol (for publication) | D4_Patient card NL | 1 |
| Protocol (for publication) | D4_Patient card Spanish | 1 |
| Protocol (for publication) | D4_Patient card_ | 1 |
| Protocol (for publication) | D4_Patient card_Czech_FP | 1.0 |
| Protocol (for publication) | D4_QLQ-C30 Dutch | N/A |
| Protocol (for publication) | D4_QLQ-C30 English_FP | 3.0 |
| Protocol (for publication) | D4_QLQ-C30 French | N/A |
| Protocol (for publication) | D4_QLQ-C30 German | N/A |
| Protocol (for publication) | D4_QLQ-C30 Spanish | N/A |
| Protocol (for publication) | D4_QLQ-C30_Czech | N/A |
| Protocol (for publication) | D5_CARMAN_Ibrutinib_IMP procedures_FP | 1 |
| Protocol (for publication) | D5_IPM ERP-X19_FP | 2.0 |
| Recruitment arrangements (for publication) | CARMAN_CTA_Overview_SubmDocs_Part-II-NLD_v1_24JUL2024 | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arragements | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arragements_for CZ_FP | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arragements_FP | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_FR | 2.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_Public | NA |
| Subject information and informed consent form (for publication) | CARMAN_PlaceholderDoc_ArmA | NA |
| Subject information and informed consent form (for publication) | CARMAN_PlaceholderDoc_ArmB-older | NA |
| Subject information and informed consent form (for publication) | CARMAN_PlaceholderDoc_ArmB-younger | NA |
| Subject information and informed consent form (for publication) | CARMAN_PlaceholderDoc_PatCard | NA |
| Subject information and informed consent form (for publication) | L1_ CARMAN_NL_PIC_Main Study_Redacted | 3 NL |
| Subject information and informed consent form (for publication) | L1_CARMAN_CZECH_PIC_additional scientific samples_FP | 1.2 |
| Subject information and informed consent form (for publication) | L1_CARMAN_CZECH_PIC_Main Study_FP | 1.4 |
| Subject information and informed consent form (for publication) | L1_CARMAN_GERMAN_PIC_additional scientific samples | 1.2 |
| Subject information and informed consent form (for publication) | L1_CARMAN_GERMAN_PIC_Main Study_FP | 1.2 |
| Subject information and informed consent form (for publication) | L1_CARMAN_PIC_Main Study_redacted | 3.3 |
| Subject information and informed consent form (for publication) | L1_CARMAN_SPAIN_PIC_additional scientific samples | 4.0 |
| Subject information and informed consent form (for publication) | L1_CARMAN_SPAIN_PIC_Main Study_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_CARMAN_SPAIN_PIC_Main Study_TC_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_Genetic ICF_FR_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_ICF additional scientific samples_FR redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_Imbrubica_patient leaflet-information_Czech_20 Sep 2024_FP | NA |
| Subject information and informed consent form (for publication) | L1_imbruvica-patient leaflet-information_Czech_FP | NA |
| Subject information and informed consent form (for publication) | L1_Study ICF FR redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_Tecartus_patient leaflet-information_Czech_02 Jun 25_FP | NA |
| Subject information and informed consent form (for publication) | L1_Tecartus-patient leaflet-information_Czech_FP | NA |
| Subject information and informed consent form (for publication) | L2_CARMAN_Quality of life_NHL-HG29 Czech_FP | NA |
| Subject information and informed consent form (for publication) | L2_CARMAN_Quality of life_NHL-HG29 German_FP | NA |
| Subject information and informed consent form (for publication) | L2_CARMAN_Quality of life_QLQ-C30 Czech_FP | 3.0 |
| Subject information and informed consent form (for publication) | L2_CARMAN_Quality of life_QLQ-C30 German_FP | 3.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Imbruvica | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Tecartus | NA |
| Synopsis of the protocol (for publication) | D1_CARMAN_ Synopsis_CZ | 2.3 |
| Synopsis of the protocol (for publication) | D1_CARMAN_Synopsis ES | 2.3 |
| Synopsis of the protocol (for publication) | D1_CARMAN_Synopsis FR | 2.3 |
| Synopsis of the protocol (for publication) | D1_CARMAN_Synopsis NL | 2.3 |
| Synopsis of the protocol (for publication) | D1_CARMAN_Synopsis_EN | 2.3 |
Application history
11 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-06-21 | Germany | Acceptable 2023-07-28
|
2023-11-27 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-11-06 | Acceptable | 2024-12-20 | |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-11-06 | Acceptable | 2024-12-04 | |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-11-12 | Germany | Acceptable | 2024-12-19 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-01-21 | Acceptable | 2025-02-19 | |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-02-19 | Germany | 2025-02-19 | |
| 7 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-08-12 | Germany | Acceptable 2025-10-10
|
2025-10-13 |
| 8 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-11-19 | Acceptable | 2025-12-18 | |
| 9 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-12-19 | Germany | Acceptable | 2025-12-19 |
| 10 | SUBSTANTIAL MODIFICATION | SM-7 | 2025-12-19 | Germany | Acceptable | 2026-01-22 |
| 11 | SUBSTANTIAL MODIFICATION | SM-9 | 2026-03-03 | Acceptable | 2026-03-06 |