Nemtabrutinib with CAR T Therapy for Relapsed/Refractory Mantle Cell Lymphoma
This study is testing a combination of two treatments, nemtabrutinib and brexucabtagene autoleucel (brexu-cel), for people with mantle cell lymphoma that has returned or not responded to previous treatments. Nemtabrutinib is a drug that may stop cancer cell growth by blocking certain enzymes. Brexu-cel is a type of CAR T-cell therapy, where your own immune cells are specially changed to fight cancer. You may be able to join if you are at least 18 years old and meet the requirements for standard brexu-cel therapy. The main goal is to see how long people live without their cancer getting worse after receiving brexu-cel, with follow-up for up to 5 years. The current recruitment status is unclear.
- Study design
- This is an interventional study with a planned enrollment of 25 participants. It is testing the combination of two treatments.
- What's involved
- You would receive nemtabrutinib by mouth daily before and after brexu-cel. Brexu-cel is given as a single intravenous (IV) infusion. Nemtabrutinib treatment could continue for up to 2 years.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants will be followed for up to 5 years after brexu-cel infusion to track how long they live without their disease progressing.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT07673367
Nemtabrutinib With CAR T Therapy in Relapsed/Refractory Mantle Cell Lymphoma
Recruiting
PHASE2Ages 18+InterventionalTreatmentVanderbilt-Ingram Cancer CenterInvestigator-initiated
~25 participants
Updated 2026-08-17 on ClinicalTrials.gov
What's tested:NemtabrutinibBrexucabtagene autoleucel ( other names: brexu-cel , Tecartus)
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Progression-free survival after brexucabtagene autoleucel (brexu-cel) infusion in relapsed/refractory mantle cell lymphoma
Measured over 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
Conditions
NCT07673367
Where you'd take part
This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
Vanderbilt University/Ingram Cancer Center
Nashville, Tennesseestudy coordinator listed
Recruiting
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Study leadership
- Bhagirathbhai Dholaria · PRINCIPAL_INVESTIGATOR · Vanderbilt University/Ingram Cancer Center
Who to contact
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Eligibility criteria
Inclusion
• 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
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
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 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)
Platelets ≥ 25000/uL (within 10 days prior to treatment initiation with nemtabrutinib in both pre-CAR and post-CAR T phase)
Hemoglobin ≥ 7 g/dL (within 10 days prior to treatment initiation with nemtabrutinib in both pre-CAR and post-CAR T phase)
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 \[CrCl\])
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
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:
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
Exclusion
• 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
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
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
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
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
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
What this trial measures
- Progression-free survival after brexucabtagene autoleucel (brexu-cel) infusion in relapsed/refractory mantle cell lymphomaFrom 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
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).