Open-label, single-arm, single center pilot study to assess safety and feasibility of administering dexamethasone intrathecally and simvastatin orally during axicabtagene ciloleucel (axi-cel) treatment. Feasibility will be measured by the proportion of patients completing two-thirds (2/3) of their assigned treatments. The study will be deemed feasible if 2/3 or more of the patients complete 2/3 or more of their allocated treatments.
This trial gathers preliminary information on the potential effect of the combination of dexamethasone and simvastatin on treating Neurotoxicity (NT) in the patient population. The rate of patients completing all required study treatments and the rate of NT will be determined. Simvastatin 40 mg/day will be started at least 5 days prior to apheresis and will be continued until day +30 after infusion. Intrathecal dexamethasone 8 mg will be administered on days (related to CAR-T infusion) -1, +6, +13, (+/- 2 days). CSF samples (3 ml) will be collected at these time points. Peripheral blood samples of 4 ml will be collected on days -1, +1, +6, and +13. The care team will check weekly CK and LFTs to ensure safety of simvastatin. Patients who develop NT will be allowed to continue treatment if feasible along with standard of care management.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
37
Simvastatin 40 mg started 2 weeks (+/-5 days) prior to apheresis through day +30
Intrathecal dexamethasone 8 mg on days -1, +6, +13 (+/-2 days)
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Number of patients completing two-thirds of their assigned treatment
The feasibility of administering Simvastatin and Dexamethasone will be measured by the proportion of the patients completing two-thirds (2/3) of their assigned treatments.
Time frame: 30 days after initiation of CAR-T therapy
Number of patients experiencing adverse events
Safety of administering Simvastatin and Dexamethasone will be measured by the proportion of patients experiencing adverse events related to the study treatment.
Time frame: From the day of 1st dose of simvastatin and until day +7 after the last dose of simvastatin.
The change in IL-6 levels
Pre- and post-infusion levels of a cytokine profile will be measured by a Lumina multiplex array in the serum and CSF of patients at time of CRS and NT if samples available.
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in IL-8 levels
Pre- and post-infusion levels of a cytokine profile will be measured by a Lumina multiplex array in the serum and CSF of patients at time of CRS and NT if samples available.
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in IL-10 levels
Pre- and post-infusion levels of a cytokine profile will be measured by a Lumina multiplex array in the serum and CSF of patients at time of CRS and NT if samples available.
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in MCP-1 levels
Pre- and post-infusion levels of a cytokine profile will be measured by a Lumina multiplex array in the serum and CSF of patients at time of CRS and NT if samples available.
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Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in VEGF levels
Pre- and post-infusion levels of a cytokine profile will be measured by a Lumina multiplex array in the serum and CSF of patients at time of CRS and NT if samples available.
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in PDGFR levels
Pre- and post-infusion levels of a cytokine profile will be measured by a Lumina multiplex array in the serum and CSF of patients at time of CRS and NT if samples available.
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in cleaved-caspase 3 levels
Pre- and post-infusion levels of a cytokine profile will be measured by a Lumina multiplex array in the serum and CSF of patients at time of CRS and NT if samples available.
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
Number of participants experiencing severe NT
The incidence of severe NT in patients receiving CAR-T cell dexamethasone and simvastatin.
Time frame: 30 days after initiation of CAR-T therapy
Number of participants experiencing overall best response with CAR-T cell therapy
The overall response rate of CAR-T cells as defined by Lugano criteria.
Time frame: 30 days after initiation of CAR-T therapy
The change in serum levels of ANG1 with statin therapy
ANG1 levels in serum will be measured using an enzyme-linked immunosorbent assay (ELISA)
Time frame: 30 days after initiation of CAR-T therapy
The change in serum levels of ANG2 with statin therapy
ANG2 levels in serum will be measured using an enzyme-linked immunosorbent assay (ELISA)
Time frame: 30 days after initiation of CAR-T therapy
The change in serum levels of IP10 with statin therapy
IP10 levels in serum will be measured using an enzyme-linked immunosorbent assay (ELISA)
Time frame: 30 days after initiation of CAR-T therapy