Health TrialsbyHealthPanel

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

ConditionsRecurrent Mantle Cell LymphomaRefractory Mantle Cell Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorVanderbilt-Ingram Cancer Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

• 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

Disqualifiers

• 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

Trial design

Design model

Single group

Treatments tested in this trial

  • Nemtabrutinib

    Drug

    Given PO

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

    Drug

    single IV administration

Treatment groups

25 Participants
are divided into 1 treatment group
Group A: Nemtabrutinib + brexu-celExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

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).

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

Secondary outcomes

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

Time frame
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.

Time frame
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.

Time frame
Day of CAR T infusion until up to 5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Vanderbilt-Ingram Cancer Center

Lead sponsor

Merck Sharp & Dohme LLC

Collaborator

Source ClinicalTrials.gov
Apply now