Neurotoxicity Prophylaxis With Intrathecal Dexamethasone and Simvastatin Post Axi-Cel

NCT ID: NCT04514029

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-06
• Study Completion Date: 2026-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Simvastatin and Dexamethasone

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).

Group Type: EXPERIMENTAL

Simvastatin

Intervention Type: DRUG

Simvastatin 40 mg started 2 weeks (+/-5 days) prior to apheresis through day +30

Dexamethasone

Intervention Type: DRUG

Intrathecal dexamethasone 8 mg on days -1, +6, +13 (+/-2 days)

Interventions

Simvastatin

Simvastatin 40 mg started 2 weeks (+/-5 days) prior to apheresis through day +30

Intervention Type: DRUG

Dexamethasone

Intrathecal dexamethasone 8 mg on days -1, +6, +13 (+/-2 days)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18- 80 years of age
• One of the following histologies:

• Diffuse large B-cell lymphoma (DLBCL) not otherwise specified, or
• Primary mediastinal B-cell lymphoma, or
• High grade B-cell lymphoma, or
• DLBCL arising from follicular lymphoma
• Disease status:

• Chemotherapy refractory disease after ≥2 lines of chemotherapy, or
• Relapsed with no remission after ≥1 lines of salvage chemotherapy, or
• Relapsed following autologous hematopoeitic stem cell transplantation (and failed at least 2 prior lines of therapy including high dose chemotherapy). If salvage therapy is given post auto HCT, the subject must have no complete response, or relapse after the last line of therapy
• Performance Status

• ECOG performance status 0-2
• Adequate organ function defined as:

• Renal function defined as:

• eGFR ≥ 30 mL/min/1.73 m^2
• Liver function defined as:

• ALT and AST ≤ 5 times the ULN for age (unless due to disease)
• Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• Hemodynamically stable and LVEF ≥ 40% confirmed by echocardiogram or MUGA
• Women of childbearing potential and men with partners of child-bearing potential must agree to use of contraception for the duration of treatment as outlined in axi-cel protocol.
• Able to provide written voluntary consent (or LAR consent for adults with diminished capacity) prior to the performance of any research related tests or procedures
• Availability of a certified practitioner to perform the lumbar punctures

Exclusion Criteria

• Allergies, or intolerance to simvastatin or dexamethasone
• Already receiving a statin drug for hypercholesterolemia and unwilling to change medication to 40 mg/day of simvastatin
• Active uncontrolled CNS lymphoma. Patients with history of CNS lymphoma who have been adequately treated are eligible
• Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD).
• Uncontrolled active hepatitis B or hepatitis C
• Active HIV infection
• Uncontrolled acute life threatening bacterial, viral or fungal infection
• Unstable angina and/or myocardial infarction
• Risk factors that preclude a safe lumbar puncture (high intracranial pressure, bleeding diathesis that cannot be reversed or corrected, need for uninterrupted anticoagulation, platelets < 50K that cannot be corrected with transfusional support
• Pregnant or breastfeeding as agents used in this study are Pregnancy Category C (dexamethasone) and X (simvastatin). Females of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days of study registration.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Maakaron, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

2019LS161

Identifier Type: -

Identifier Source: org_study_id