Neurotoxicity Prophylaxis With Intrathecal Dexamethasone and Simvastatin Post Axi-Cel

NCT04514029 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 2019LS161
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma

Keywords

Lymphoma; CAR-T; Neurotoxicity; CRS; Dexamethasone; Simvastatin

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  From the day of 1st dose of simvastatin and until day +7 after the last dose of simvastatin.

Secondary Outcomes (12)

• The change in IL-6 levels

  One day prior to infusion and at days +1,+6, and +13 post infusion

• The change in IL-8 levels

  One day prior to infusion and at days +1,+6, and +13 post infusion

• The change in IL-10 levels

  One day prior to infusion and at days +1,+6, and +13 post infusion

• The change in MCP-1 levels

  One day prior to infusion and at days +1,+6, and +13 post infusion

• The change in VEGF levels

  One day prior to infusion and at days +1,+6, and +13 post infusion

Study Arms (1)

Simvastatin and Dexamethasone

EXPERIMENTAL

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).

Drug: Simvastatin; Drug: Dexamethasone

Interventions

Simvastatin DRUG

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

Simvastatin and Dexamethasone

Dexamethasone DRUG

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

Simvastatin and Dexamethasone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Lymphoma; Neurotoxicity Syndromes

Interventions

Simvastatin; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Study Officials

• Joseph Maakaron, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2020
• First Posted: August 14, 2020
• Study Start: August 6, 2020
• Primary Completion: November 3, 2023
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 8, 2026

Record last verified: 2026-01

Locations

US (1)