Mantle Cell LymphomaPhase 2CARMANNCT06482684
CAR-T-cell Treatment for Untreated High Risk MANtle Cell Lymphoma
A Phase 2 study testing KTE-X19 and Ibrutinib in people with Mantle Cell Lymphoma, run by Christian Schmidt, MD at 2 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Mantle Cell Lymphoma
- What is being tested?
- KTE-X19 and Ibrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 2 sitesGermany
- Study dates
- 15 Feb 2024to 31 Dec 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of MCL according to WHO classification, with documentation of either overexpression of cyclin D1 or presence of t(11;14)
- 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)
- No prior treatment for MCL
- Stage II-IV (Ann Arbor)
- 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.
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- ECOG performance status ≤ 2
- The following laboratory values at screening (unless discrepancies are related to MCL):
- 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)
- 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 6 months after the last dose of KTE-X19 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
Who cannot join
- Subjects not able to give consent
- 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 in follow 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
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- Serious concomitant disease interfering with a regular therapy according to the study protocol:
- 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)
- 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.
- 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
- 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
- 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 immunosuppression / systemic medication within the last 2 years
- History of deep vein thrombosis or pulmonary embolism requiring therapeutic anticoagulation within 6 months of enrolment
- Known severe primary immunodeficiency
- Any medical condition likely to interfere with assessment of 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Germany2 sites, 2 recruiting
- Recruiting
University Hospital of Mainz
Mainz
Georg Hess, MD, +49 6131 175040, georg.hess@unimedizin-mainz.de
- Recruiting
Klinikum der Universität München
Munich, 81377
Christian Schmidt, MD, +49 (0)89 4400-77907
Christian Schmidt, MD, +49 (0)89 4400-77907, Christian_Schmidt@med.uni-muenchen.de
About this study
Official title: 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)
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.
Read the 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.
- Conditions
- Mantle Cell Lymphoma
- Being tested
- KTE-X19, Ibrutinib
- Keywords
- High Risk MCL, CAR-T-Cells, MCL Firstline Treatment
- Medical subject headings
- Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KTE-X19Drug
See description of treatment arms
IbrutinibDrug
See description of treatment arms
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | The abbreviated induction phase consists of 2 cycles of Ibrutinib + Rituximab and 2 cycles of Ibrutinib + R-CHOP for primary tumor reduction followed by CAR-T-cell treatment. In case of good clinical response (PR or CR) after 2 cycles of Ibrutinib + Rituximab, Ibrutinib + R-CHOP can be omitted. In this case, one cycle of Ibrutinib monotherapy will be applied. T cell apheresis will be performed after the initial 2 cycles. Application of KTE-X19 will be performed after lymphodepleting chemotherapy with Fludarabine and Cyclophosphamide (FC). After stable hematopoietic recovery, maintenance with Ibrutinib will be applied for 6 months but not prior to day 60 post CAR. The follow-up period starts after the completion of Ibrutinib maintenance and takes 4.5 up to 7 years. Receives: Drug: KTE-X19; Drug: Ibrutinib |
| Arm B | Active comparator | Younger patients (≤ 65 years) will receive 3 cycles R-CHOP + Ibrutinib/ 3 cycles R-DHAP alternating, followed by autologous stem cell transplantation (ASCT). Elderly patients (≥ 65 years) will receive 6 cycles of Bendamustine and Rituximab + Ibrutinib or R-CHOP + Ibrutinib without ASCT. Independently of age, control patients receive 2 years of maintenance therapy with Ibrutinib and 3 years of Rituximab maintenance if foreseen by national guidelines, in addition to Ibrutinib maintenance. Receives: Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Failure Free Survival
Time from randomization to any discontinuation of the per protocol treatment due to stable or progressive disease during induction, stable disease at the end of induction, progressive disease at any time after end of induction treatment and death from any cause, whichever occurred first. Stable disease at end of induction is defined as failure event because it represents a regular indication for salvage treatment in MCL.
Measured: From Randomization to any to any discontinuation of the per protocol treatment due to stable or progressive disease
Secondary outcomes (4)
Progression-free survival (PFS)
Measured: from the date of response (CR or PR within 6 months from randomization) to progression or death from any cause
Complete remission (CR) rate
Measured: 6 months from randomization until end of trial
Time to first response
Measured: date of randomization to the date of first response (CR or PR)
Overall survival
Measured: day 1 after randomization until end of trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2024
- Study start15 Feb 2024
- Primary completion15 Jun 2031 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mantle Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Christian Schmidt, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz
- Responsible party
- Sponsor-investigator, Christian Schmidt, MD, Ludwig-Maximilians - University of Munich
- Investigators
- Georg Hess, MD, Principal investigator, Johannes Gutenberg University Mainz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06482684
- Sponsor's protocol ID
- CARMAN
- Other IDs
- 2022-502405-15-01
- Acronym
- CARMAN
- Status last verified
- Jun 2024
- First submitted
- 26 Jun 2024
- Last updated
- 1 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Silkenstedt E, Dreyling M. First Line Therapy in Mantle Cell Lymphoma-The Role of BTKi in the Initial Treatment of Transplant-Eligible and -Ineligible Patients. Hematol Oncol. 2025 Jun;43 Suppl 2(Suppl 2):e70073. doi: 10.1002/hon.70073.
PubMed 40517546
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06482684
- Acronym / sponsor ID
- CARMAN / CARMAN
- Conditions
- Mantle Cell Lymphoma
- Keywords
- High Risk MCL, CAR-T-Cells, MCL Firstline Treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Christian Schmidt, MDUniversity, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz
- Study start
- 15 Feb 2024 (actual)
- Primary completion
- 15 Jun 2031 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 1 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: KTE-X19, Drug: IbrutinibThe abbreviated induction phase consists of 2 cycles of Ibrutinib + Rituximab and 2 cycles of Ibrutinib + R-CHOP for primary tumor reduction followed by CAR-T-cell treatment. In case of good clinical response (PR or CR) after 2 cycles of Ibrutinib + Rituximab, Ibrutinib + R-CHOP can be omitted. In this case, one cycle of Ibrutinib monotherapy will be applied. T cell apheresis will be performed after the initial 2 cycles. Application of KTE-X19 will be performed after lymphodepleting chemotherapy with Fludarabine and Cyclophosphamide (FC). After stable hematopoietic recovery, maintenance with Ibrutinib will be applied for 6 months but not prior to day 60 post CAR. The follow-up period starts after the completion of Ibrutinib maintenance and takes 4.5 up to 7 years. |
| Arm B | Active comparator | Drug: IbrutinibYounger patients (≤ 65 years) will receive 3 cycles R-CHOP + Ibrutinib/ 3 cycles R-DHAP alternating, followed by autologous stem cell transplantation (ASCT). Elderly patients (≥ 65 years) will receive 6 cycles of Bendamustine and Rituximab + Ibrutinib or R-CHOP + Ibrutinib without ASCT. Independently of age, control patients receive 2 years of maintenance therapy with Ibrutinib and 3 years of Rituximab maintenance if foreseen by national guidelines, in addition to Ibrutinib maintenance. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically confirmed diagnosis of MCL according to WHO classification, with documentation of either overexpression of cyclin D1 or presence of t(11;14)
- 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)
- No prior treatment for MCL
- Stage II-IV (Ann Arbor)
- 18-75 years
Key exclusion criteria (20 listed)
- Subjects not able to give consent
- 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 in follow 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KTE-X19See description of treatment arms | Drug | Arm A |
| IbrutinibSee description of treatment arms | Drug | Arm A, Arm B |
Primary outcome
Failure Free Survival
Time frame: From Randomization to any to any discontinuation of the per protocol treatment due to stable or progressive disease
Time from randomization to any discontinuation of the per protocol treatment due to stable or progressive disease during induction, stable disease at the end of induction, progressive disease at any time after end of induction treatment and death from any cause, whichever occurred first. Stable disease at end of induction is defined as failure event because it represents a regular indication for salvage treatment in MCL.
4 secondary outcomes
Progression-free survival (PFS)
Time frame: from the date of response (CR or PR within 6 months from randomization) to progression or death from any cause
Complete remission (CR) rate
Time frame: 6 months from randomization until end of trial
Time to first response
Time frame: date of randomization to the date of first response (CR or PR)
Overall survival
Time frame: day 1 after randomization until end of trial
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2024.
- Derived from this study: PubMed 40517546Silkenstedt E, Dreyling M. First Line Therapy in Mantle Cell Lymphoma-The Role of BTKi in the Initial Treatment of Transplant-Eligible and -Ineligible Patients. Hematol Oncol. 2025 Jun;43 Suppl 2(Suppl 2):e70073. doi: 10.1002/hon.70073.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Georg Hess, MD principal investigator
Johannes Gutenberg University Mainz
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KTE-X19 and Ibrutinib in people with Mantle Cell Lymphoma, run by Christian Schmidt, MD at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Martin Dreyling, MD (+4989440074900, Martin.Dreyling@med.uni-muenchen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Failure Free Survival (time frame: From Randomization to any to any discontinuation of the per protocol treatment due to stable or progressive disease). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06482684, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2024.