Study on CAR-T-cell Therapy with Rituximab and Ibrutinib for Patients with High-Risk Mantle Cell Lymphoma

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What is this study about?

This clinical trial is focused on studying a type of cancer called Mantle Cell Lymphoma (MCL), which is a rare form of non-Hodgkin’s lymphoma. The study aims to explore the effectiveness of a treatment strategy using a special type of therapy known as CAR-T-cell treatment with a medication called KTE-X19. This treatment involves using the patient’s own immune cells, which are modified to better fight cancer cells. The trial will compare this approach to the standard treatment methods currently used for patients with high-risk MCL.

Participants in the study will be divided into two groups. One group will receive the experimental treatment, which includes a combination of Rituximab and Ibrutinib followed by the CAR-T-cell therapy. The other group will receive the standard treatment, which is the usual care provided for MCL. The study will also involve the use of several other medications, including Thiotepa, Cisplatin, Etoposide, Melphalan, Cytarabine, Cyclophosphamide, Doxorubicin, Filgrastim, Oxaliplatin, Prednisolone, Bendamustine, Carmustine, Pegfilgrastim, Fludarabine, Vincristine Sulfate, Rituximab, Dexamethasone, and Tocilizumab, which are used to support the treatment process.

The purpose of the study is to compare the effectiveness of the CAR-T-cell treatment strategy with the standard treatment in patients who have not been treated for MCL before. Participants will undergo a series of treatments and follow-ups over a period of time to monitor their response to the therapy. The study will help determine if the new treatment approach can improve outcomes for patients with high-risk MCL compared to the current standard of care.

1 joining the study

Upon joining the study, the patient is assigned to one of two treatment groups: experimental treatment (Arm A) or standard care (Arm B).

The study focuses on patients with high-risk mantle cell lymphoma (MCL).

2 induction therapy

In Arm A, the patient receives an abbreviated induction therapy with rituximab and ibrutinib. Rituximab is administered through an intravenous infusion, while ibrutinib is taken orally in the form of 140 mg hard capsules.

In Arm B, the patient undergoes standard induction therapy, which may include a combination of medications such as cyclophosphamide, doxorubicin, vincristine sulfate, and prednisolone, all administered through intravenous infusion or oral routes as specified by the healthcare provider.

3 CAR-T-cell treatment

Patients in Arm A receive CAR-T-cell treatment with brexucabtagene autoleucel (Tecartus), administered as an intravenous infusion.

This step involves the collection and modification of the patient’s T-cells to target cancer cells more effectively.

4 maintenance therapy

In Arm A, the patient continues with ibrutinib maintenance therapy for 6 months, taking the medication orally.

In Arm B, the patient follows the standard maintenance therapy as determined by the healthcare provider, which may include medications like rituximab and others as needed.

5 monitoring and follow-up

Throughout the trial, the patient’s health and response to treatment are closely monitored through regular check-ups and tests.

The primary goal is to assess failure-free survival, progression-free survival, and overall response rates, among other outcomes.

Who Can Join the Study?

Must have a confirmed diagnosis of Mantle Cell Lymphoma (MCL) according to the World Health Organization classification, with specific markers like overexpression of cyclin D1 or presence of a genetic change called t(11;14).
Age between 18 and 75 years.
Must have at least one measurable tumor or lesion, as defined by specific medical criteria. If the cancer is only in the bone marrow, a bone marrow test is required.
Must have an ECOG performance status of 2 or less, which means the patient is able to carry out all self-care but unable to carry out any work activities.
Must have certain laboratory test results within specific ranges, unless the results are affected by MCL:
- White blood cells called neutrophils must be at least 1000 cells per microliter.
- Platelets, which help with blood clotting, must be at least 75,000 cells per microliter.
- Creatinine, a waste product in the blood, must be less than 2 mg/dL, or the kidney function test called creatinine clearance must be at least 60 mL/min.
- Transaminases (AST and ALT), which are liver enzymes, must be less than 2.5 times the upper limit of normal.
- Total bilirubin, a substance made during the breakdown of red blood cells, must be less than or equal to 2 times the upper limit of normal, unless there is another known reason.
No evidence of disease in the central nervous system (CNS).
Available only in France.
Must provide written informed consent and be able to follow study instructions and attend all required visits.
Sexually active men and women who can have children must agree to use highly effective birth control methods during the study and for a period after the study ends.
Women who can have children must have a negative pregnancy test. Women who have been surgically sterilized or are postmenopausal for at least 2 years are not considered to be of childbearing potential.
Must agree not to drive a motor vehicle for 8 weeks after receiving CAR T cell treatment.
Must be able to reach the study site within 2 hours in case of an emergency.
Must have at least one high-risk feature of MCL, such as a high score on a specific risk index (MIPI-c) or a genetic mutation called TP53.
No prior treatment for MCL.
Cancer must be at stage II-IV according to the Ann Arbor staging system.

Who Cannot Join the Study?

Patients who have already received treatment for Mantle Cell Lymphoma (MCL) cannot participate. Mantle Cell Lymphoma is a type of cancer that affects the lymph nodes.
Patients who are not considered high risk for Mantle Cell Lymphoma are excluded. High risk means the disease is more likely to progress quickly or be more severe.
Patients who are not within the specified age range for the study cannot participate. The study is open to certain age groups only.
Patients who are part of a vulnerable population may not be eligible. Vulnerable population refers to groups who may have additional risks or challenges, such as children, pregnant women, or those with certain disabilities.
Patients who do not meet other specific health criteria set by the study may be excluded. These criteria ensure the safety and appropriateness of the study for participants.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Hospital Universitario Y Politecnico La Fe	Valencia	Spain
University Hospital Of Clermont-Ferrand	Clermont Ferrand	France
Universitaetsmedizin Goettingen	Goettingen	Germany
Center For Pediatric And Adolescent Medicine Of The Johannes Gutenberg University Mainz	Mainz	Germany
Hospital Universitario De Salamanca	Salamanca	Spain
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France
Centre Hospitalier Universitaire De Lille	Lille	France
Universitaet Leipzig	Leipzig	Germany

Other Sites

Site Name	City	Country
Charite Universitaetsmedizin Berlin KöR	Berlin	Germany
Hospital General Universitario Gregorio Maranon	Madrid	Spain
Hospital Universitario 12 De Octubre	Madrid	Spain
Virgen del Rocío University Hospital	Sevilla	Spain
Hospital Clinic De Barcelona	Barcelona	Spain
Fakultni Nemocnice Brno	Brno	Czechia
Saarland University Hospital	Homburg	Germany
Centre Hospitalier Universitaire De Montpellier	Montpellier	France
Medical Center – University Of Freiburg	Freiburg Im Breisgau	Germany
Centre Hospitalier Universitaire De Nantes	Nantes	France
Vseobecna Fakultni Nemocnice V Praze	Prague	Czechia
Centre Hospitalier Universitaire De Rennes	Rennes	France
Institut fuer Klinische Transfusionsmedizin und Immungenetik Ulm gGmbH	Ulm	Germany
Universitaetsklinikum Schleswig-Holstein AöR	Kiel	Germany
HELIOS Klinikum Berlin-Buch GmbH	Berlin	Germany
Centre Hospitalier Lyon Sud	Pierre Benite	France
Hopital Beaujon	Clichy	France
Westfaelische Wilhelms Universitaet Muenster	Munster	Germany
Uivaitailuvz Mlarnhm Crjcekt Gfzkbdqlj	Groningen	The Netherlands
Iyextrco Ccajva Dvatgugrktzqxgkti	L'hospitalet De Llobregat	Spain
Uxwexguzey Hbrbpucw Cfexnde	Cologne	Germany
Ckznxj Hgonvqbbovy Ugxfmfqlasjfb Dc Ddads	Dijon	France
Auzckyavl Utf	Amsterdam	The Netherlands
Uvpxtenvwbmhhrieupihb Djdykspbwxe Abv	Duesseldorf	Germany
Egcjqsg Umkmfrbxohqo Muisgvp Cbesoms Rxtjbmjzf (eluqkeu Mzj	Rotterdam	The Netherlands
Gijjak Uyvhzituin Fjzmpfgbd	Frankfurt	Germany
Ktvmhjry dlh Usnsaxheaiim Mvnggndn Aml	Munich	Germany
Ucbzbivaoxgfechllarhk Wvvnlcvcs Azd	Wuerzburg	Germany
Usshtigpgf Mpoztfb Cjcuqc Hqcpdiexyorjlvqbp	Hamburg	Germany
Uleplufbmviaghzvnofjx Epcks Ati	Essen	Germany
Hndfmjiz Vpof dzdymmvl	Barcelona	Spain
Irzihdqs Pwxzuanupaaubjd Cxixcw Cwwisl	Marseille	France

Trial status

Country	Status	Recruitment Start
Czechia	Recruiting	01.09.2023
France	Recruiting	01.09.2023
Germany	Recruiting	01.09.2023
Spain	Recruiting	01.09.2023
The Netherlands	Recruiting	01.09.2023

Trial locations

Investigated drugs:

Rituximab is a medication used to treat certain types of cancer, including mantle cell lymphoma. It works by targeting specific proteins on the surface of cancer cells, helping the immune system to destroy them. In this trial, Rituximab is used as part of an initial treatment to help reduce the number of cancer cells.

Ibrutinib is a medication that helps to slow down or stop the growth of cancer cells. It is used in this trial to treat mantle cell lymphoma by interfering with the pathways that cancer cells use to grow and survive. Ibrutinib is given both during the initial treatment phase and as a maintenance therapy to help keep the cancer from returning.

KTE-X19 is a type of CAR-T-cell therapy used in this trial. CAR-T-cell therapy involves modifying a patient’s own immune cells to better recognize and attack cancer cells. KTE-X19 is specifically designed to target mantle cell lymphoma cells, offering a personalized approach to treatment. This therapy is used after the initial treatment phase to intensify the treatment and improve outcomes for patients with high-risk mantle cell lymphoma.

Investigated diseases:

Mantle Cell Lymphoma – Mantle Cell Lymphoma (MCL) is a type of non-Hodgkin lymphoma that originates from B-cells, which are a type of white blood cell. It typically begins in the outer edge of a lymph node called the mantle zone. The disease often progresses to involve other lymph nodes, bone marrow, and sometimes the spleen and gastrointestinal tract. MCL is characterized by the overproduction of abnormal B-cells, which can lead to the enlargement of lymph nodes and other organs. As the disease advances, it can cause symptoms such as fatigue, fever, night sweats, and weight loss. The progression of MCL can vary, with some cases advancing more rapidly than others.

Trial ID:

2022-502405-15-01

Protocol code:

CARMAN

Trial Phase:

Therapeutic exploratory (Phase II)

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Study on CAR-T-cell Therapy with Rituximab and Ibrutinib for Patients with High-Risk Mantle Cell Lymphoma

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?