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Recurrent Mantle Cell LymphomaPhase 2NCT07673367

Nemtabrutinib With CAR T Therapy in Relapsed/Refractory Mantle Cell Lymphoma

A Phase 2 study testing Nemtabrutinib and Brexucabtagene autoleucel ( other names: brexu-cel , Tecartus) in people with Recurrent Mantle Cell Lymphoma and Refractory Mantle Cell Lymphoma, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase II trial tests the effect of nemtabrutinib in combination with brexucabtagene autoleucel (brexu-cel) in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nemtabrutinib and Brexucabtagene autoleucel ( other names: brexu-cel , Tecartus)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
31 Jul 2026to 31 Jul 2032
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • • Confirmed diagnosis of relapsed or refractory mantle cell lymphoma who meets institutional eligibility criteria to receive standard of care brexu-cel therapy
  • Is an individual of any sex/gender, who are at least 18 years of age on the day of signing informed consent with confirmed diagnosis of R/R MCL will be enrolled in this study
  • The participant (or legally acceptable representative if applicable) has provided documented informed consent/assent for the trial
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention
  • The ability to swallow and retain oral medication
  • NOTE: Administration of nemtabrutinib is not permitted through a percutaneous endoscopic gastro-jejunal (J-PEG) tube
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  • Participants who are hepatitis B virus surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to allocation
  • Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests should include HBsAg and anti-HBV. Hepatitis B screening tests are not required unless:
  • Known history of HBV infection
  • As mandated by local health authority
  • Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
  • Participants must have completed curative anti-viral therapy at least 4 weeks prior to allocation
  • Hepatitis C screening tests are not required unless:
  • Known history of HCV infection
  • As mandated by local health authority
  • Participants with HIV are eligible if they meet ALL of the following criteria:
  • The CD4 count is ≥ 350 cells/uL at screening
  • The HIV viral load is below the detectable level as per locally available testing
  • Are on a stable anti-retroviral therapy (ART) regimen for at least 4 weeks prior to study entry
  • NOTE: ART includes drugs, which are NOT strong cytochrome P450 (CYP)3A4 inducers (participants receiving ART that are strong CYP3A4 inducers are not eligible to be included in the study)
  • HIV screening tests are not required unless:
  • Known history of HIV infection
  • As mandated by local health authority or institutional standards
  • Are compliant with their ART
  • Adequate organ function as defined. Specimens must be collected within 10 days prior to treatment initiation with nemtabrutinib in both pre-CAR and post-CAR T phase
  • Absolute neutrophil count (ANC) ≥ 500/uL (within 10 days prior to treatment initiation with nemtabrutinib in both pre-CAR and post-CAR T phase)
  • Growth factor (granulocyte colony-stimulating factor [GCSF] and thyroid peroxidase [TPO] agonist) and/or transfusion support is permissible to stabilize participant at least 7 days before screening or planned start of nemtabrutinib
  • Platelets ≥ 25000/uL (within 10 days prior to treatment initiation with nemtabrutinib in both pre-CAR and post-CAR T phase)
  • Growth factor (GCSF and TPO agonist) and/or transfusion support is permissible to stabilize participant at least 7 days before screening or planned start of nemtabrutinib
  • Hemoglobin ≥ 7 g/dL (within 10 days prior to treatment initiation with nemtabrutinib in both pre-CAR and post-CAR T phase)
  • Growth factor (GCSF and TPO agonist) and/or transfusion support is permissible to stabilize participant at least 7 days before screening or planned start of nemtabrutinib
  • Creatinine ≤ 1.5 x upper limit of normal (ULN) (within 10 days prior to treatment initiation with nemtabrutinib in both pre-CAR and post-CAR T phase) OR measured or calculated creatinine clearance ≥ 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (glomerular filtration rate [GFR} can also be used in place of creatinine or creatinine clearance [CrCl])
  • Creatinine clearance (CrCl) should be calculated per institutional standard
  • Total bilirubin ≤ 1.5 x ULN (within 10 days prior to treatment initiation with nemtabrutinib in both pre-CAR and post-CAR T phase) OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 x ULN
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤ 5 x ULN (within 10 days prior to treatment initiation with nemtabrutinib in both pre-CAR and post-CAR T phase)
  • International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (within 10 days prior to treatment initiation with nemtabrutinib in both pre-CAR and post-CAR T phase) unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Participants assigned male sex at birth
  • If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
  • Nemtabrutinib: 12 days
  • Cyclophosphamide: 4 months
  • Fludarabine: 3 months
  • Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
  • Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
  • Uses a penile/external condom plus nonparticipant of childbearing potential who is not currently pregnant and should also be advised of the benefit for that partner to use an additional method of contraception, as a condom may break or leak
  • Note: Participants capable of producing ejaculate whose partner is pregnant, or breastfeeding must agree to use penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate
  • Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed
  • Participants assigned female sex at birth
  • A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a person of childbearing potential (POCBP) OR
  • Is a POCBP and:
  • Uses a contraceptive method that is highly effective (with a failure rate of < 1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
  • Nemtabrutinib: 1 month
  • Cyclophosphamide: 12 months
  • Fludarabine: 6 months
  • The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed
  • Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for urine test) or 72 hours (for serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
  • Abstains from breastfeeding during the study intervention period and for at least 30 days after study intervention with nemtabrutinib
  • Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy

Who cannot join

  • • Gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy)
  • Diagnosis of Richter transformation including any history of Richter's transformation
  • Active central nervous system (CNS) involvement with lymphoma. Previously treated CNS disease allowed as long as confirmed disease control based on imaging and negative cerebrospinal fluid (CSF) cytology
  • Active infection requiring systemic therapy, including IV antibiotics during screening. Participants may be rescreened following completion of IV antibiotic course (24 hour washout period required). PO antibiotics are allowed if infection is considered controlled by treating physician
  • AIDS defining opportunistic infection in the past 12 months prior to screening
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
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  • Corrected QT interval (QTc) prolongation (defined as a Fridericia's formula-corrected QT interval [QTcF] > 450 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
  • Known allergy/sensitivity (≥ grade 3) to nemtabrutinib or any of the excipients
  • History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding
  • History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
  • NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of bladder or cervix
  • A POCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
  • Patients with refractory MCL to non-covalent BTK inhibitor such as pirtobrutinib or nemtabrutinib. Patients who have relapsed or refractory MCL after prior covalent BTK inhibitors are allowed. Patients who have received prior non-covalent BTK inhibitors and achieved at least partial response are allowed
  • Currently being treated with the following drugs:
  • P-glycoprotein (P-gp) substrates with a narrow therapeutic index
  • CYP3A strong inducers
  • CYP3A strong inhibitors
  • NOTE: A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a participant to be eligible for study enrollment
  • Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks or 5 half-lives before start of study treatment (whichever is shorter). Subjects can be screened pending required wash-out period before starting nemtabrutinib
  • Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids
  • NOTE: Two weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted
  • Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
  • Is currently enrolled on another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited
  • Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication. Hypogammaglobulinemia will not be considered state of immunodeficiency
  • Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid)
  • Has not adequately recovered after 4 weeks from major surgery or has ongoing surgical complications
  • NOTE: Biopsy and placement of central venous access devices are not considered major surgery
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Vanderbilt-Ingram Services for Timely Access contact

800-811-8480

cip@vumc.org

Vanderbilt-Ingram Services Timely Access contact

cip@vumc.org

United States1 site, 1 recruiting

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37203

    Vanderbilt-Ingram Service Services for Timely Access, 800-811-8480, cip@vumc.org

    Bhagirathbhai Dholaria

    Recruiting

Other trials in United States

About this study

Official title: A Phase 2 Trial of Nemtabrutinib in Combination With Brexu-cel for Patients With Relapsed/Refractory Mantle Cell Lymphoma

This phase II trial tests the effect of nemtabrutinib in combination with brexucabtagene autoleucel (brexu-cel) in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Nemtabrutinib, a BTK inhibitor, may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chimeric antigen receptor (CAR) T-cell therapy, such as brexu-cel, is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Chemotherapy, such as fludarabine and cyclophosphamide, are given before CAR T cell therapy to help kill cancer cells in the body and help make room for the CAR T cells. Giving nemtabrutinib in combination with brexu-cel may be safe, tolerable, and/or effective in treating patients with relapsed or refractory mantle cell lymphoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the impact of Nemtabrutinib on efficacy of brexu-cel in relapsed or refractory (R/R) mantle cell lymphoma (MCL).

SECONDARY OBJECTIVES:

  1. To evaluate disease response rates and survival after brexu-cel. II. To evaluate the safety of Nemtabrutinib with brexu-cel.

EXPLORATORY OBJECTIVES:

  1. Impact of nemtabrutinib on undetectable measurable residual disease (MRD) rate after brexu-cel.

II. Impact of Nemtabrutinib biological activity on recipient immune repertoire. III. Impact of Nemtabrutinib in vivo brexu-cel kinetics. IV. Mechanism of disease relapse.

OUTLINE:

PRE-CAR T PHASE (4-5 WEEKS): Starting 2 weeks before undergoing apheresis, patients receive nemtabrutinib orally (PO) once daily (QD) on days -40 to -6 in the absence of disease progression or unacceptable toxicity. Patients receive lymphodepleting chemotherapy fludarabine and cyclophosphamide on days -5 to -3.

CAR T INFUSION PHASE (4-5 WEEKS): Patients receive brexu-cel IV on day 0.

POST CAR T PHASE (UP TO 24 MONTHS): Starting around day 28 or later after brexu-cel infusion, patients without progressive disease (PD) receive nemtabrutinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

Additionally, patients undergo computed tomography (CT), positron emission tomography (PET)/CT or magnetic resonance imaging (MRI), bone marrow aspiration and biopsy, blood sample collection and optional tumor/lymph node biopsy throughout the study.

After completion of study treatment, patients are followed up at 30 days, 12 weeks, then every 6 months for up to 5 years.

Being tested
Nemtabrutinib, Brexucabtagene autoleucel ( other names: brexu-cel , Tecartus)
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.

  • NemtabrutinibDrug

    Given PO

  • Brexucabtagene autoleucel ( other names: brexu-cel , Tecartus)Drug

    single IV administration

Study groups in NCT07673367
Study groupRoleWhat they receive
Nemtabrutinib + brexu-celExperimentalPRE-CAR T PHASE (4-5 WEEKS): Starting 2 weeks before undergoing apheresis, patients receive nemtabrutinib orally (PO) once daily (QD) on days -40 to -6 in the absence of disease progression or unacceptable toxicity. Patients receive lymphodepleting chemotherapy fludarabine and cyclophosphamide on days -5 to -3. CAR T INFUSION PHASE (4-5 WEEKS): Patients receive brexu-cel IV on day 0. POST CAR T PHASE (UP TO 24 MONTHS): Starting around day 28 or later after brexu-cel infusion, patients without progressive disease (PD) receive nemtabrutinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Nemtabrutinib; Drug: Brexucabtagene autoleucel ( other names: brexu-cel , Tecartus)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival after brexucabtagene autoleucel (brexu-cel) infusion in relapsed/refractory mantle cell lymphoma

    Will be analyzed using Kaplan-Meier product limit methods to estimate the survival distribution, median time-to-event with 95% confidence interval, patients at risk, patients with an event, patients censored and survival probabilities at selected time points. Kaplan-Meier methods will be used to estimate the event-free curves and corresponding quartiles (including the median).

    Measured: From the day of brexu-cel infusion to the earlier of documentation of objective disease progression, initiation of any non-protocol anti-lymphoma therapy or death from any cause, assessed up to 5 years

Secondary outcomes (3)

  1. Estimate complete response (CR) rate following the infusion of CAR T cell

    This measure is lymphoma response on PET-CT scan using the Lugano criteria

    Measured: Day 28 until up to one year after CAR T infusion

  2. Number of Adverse Events After CAR-T Cell Infusion with nemtabrutinib

    This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (CTCAE ver. 5) occurring during the first 28 days following infusion. Cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) will be graded per ASTCT Criteria.

    Measured: Up to 2 years from CAR T infusion

  3. Overall survival after CAR T infusion

    This measure is proportion of surviving subjects from CAR T infusion.

    Measured: Day of CAR T infusion until up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2026
  2. Study start31 Jul 2026
  3. Primary completion31 Jul 2031 (estimated)
  4. Study completion31 Jul 2032 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07673367
Sponsor's protocol ID
VICC-VCCTT23481
Status last verified
Aug 2026
First submitted
17 Jun 2026
Last updated
17 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nemtabrutinib and Brexucabtagene autoleucel ( other names: brexu-cel , Tecartus) in people with Recurrent Mantle Cell Lymphoma and Refractory Mantle Cell Lymphoma, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.

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 58 inclusion and 31 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 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 Vanderbilt-Ingram Services for Timely Access (800-811-8480, cip@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival after brexucabtagene autoleucel (brexu-cel) infusion in relapsed/refractory mantle cell lymphoma (time frame: From the day of brexu-cel infusion to the earlier of documentation of objective disease progression, initiation of any non-protocol anti-lymphoma therapy or death from any cause, assessed up to 5 years). 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 NCT07673367.

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 17 Aug 2026.

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