LymphomaEarly Phase 1NCT04514029
Neurotoxicity Prophylaxis With Intrathecal Dexamethasone and Simvastatin Post Axi-Cel
A Early Phase 1 study testing Simvastatin and Dexamethasone in people with Lymphoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- Simvastatin and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Aug 2020to Dec 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 22Show fewer
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Neurotoxicity Prophylaxis With Intrathecal Dexamethasone and Simvastatin in Adults Receiving Axicabtagene Ciloleucel (Axi-Cel) Treatment
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.
Read the 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
- Being tested
- Simvastatin, Dexamethasone
- Keywords
- Lymphoma, CAR-T, Neurotoxicity, CRS, Dexamethasone, Simvastatin
- Medical subject headings
- Lymphoma, Neurotoxicity Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Simvastatin 40 mg started 2 weeks (+/-5 days) prior to apheresis through day +30
DexamethasoneDrug
Intrathecal dexamethasone 8 mg on days -1, +6, +13 (+/-2 days)
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Simvastatin; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 30 days after initiation of CAR-T therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2020
- Study start6 Aug 2020
- Primary completion3 Nov 2023
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joseph Maakaron, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04514029
- Sponsor's protocol ID
- 2019LS161
- Status last verified
- Jan 2026
- First submitted
- 12 Aug 2020
- Last updated
- 8 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurotoxicity Prophylaxis With Intrathecal Dexamethasone and Simvastatin in Adults Receiving Axicabtagene Ciloleucel (Axi-Cel) Treatment
- ClinicalTrials.gov ID
- NCT04514029
- Acronym / sponsor ID
- 2019LS161
- Conditions
- Lymphoma
- Keywords
- Lymphoma, CAR-T, Neurotoxicity, CRS, Dexamethasone, Simvastatin
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- 6 Aug 2020 (actual)
- Primary completion
- 3 Nov 2023 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 14 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Simvastatin and Dexamethasone | Experimental | Drug: Simvastatin, Drug: DexamethasoneSimvastatin 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). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 18- 80 years of age
- One of the following histologies:
- Disease status:
- Performance Status
- Adequate organ function defined as:
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SimvastatinSimvastatin 40 mg started 2 weeks (+/-5 days) prior to apheresis through day +30 | Drug | Simvastatin and Dexamethasone |
| DexamethasoneIntrathecal dexamethasone 8 mg on days -1, +6, +13 (+/-2 days) | Drug | Simvastatin and Dexamethasone |
Primary outcome
Number of patients completing two-thirds of their assigned treatment
Time frame: 30 days after initiation of CAR-T therapy
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.
Number of patients experiencing adverse events
Time frame: From the day of 1st dose of simvastatin and until day +7 after the last dose of simvastatin.
Safety of administering Simvastatin and Dexamethasone will be measured by the proportion of patients experiencing adverse events related to the study treatment.
12 secondary outcomes
The change in IL-6 levels
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in IL-8 levels
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in IL-10 levels
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in MCP-1 levels
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in VEGF levels
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in PDGFR levels
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
The change in cleaved-caspase 3 levels
Time frame: One day prior to infusion and at days +1,+6, and +13 post infusion
Number of participants experiencing severe NT
Time frame: 30 days after initiation of CAR-T therapy
Number of participants experiencing overall best response with CAR-T cell therapy
Time frame: 30 days after initiation of CAR-T therapy
The change in serum levels of ANG1 with statin therapy
Time frame: 30 days after initiation of CAR-T therapy
The change in serum levels of ANG2 with statin therapy
Time frame: 30 days after initiation of CAR-T therapy
The change in serum levels of IP10 with statin therapy
Time frame: 30 days after initiation of CAR-T therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
Related trials for Lymphoma
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
Not yet recruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
Ann Arbor Stage II Mantle Cell Lymphoma, Ann Arbor Stage III Mantle Cell Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Maakaron, MD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Simvastatin and Dexamethasone in people with Lymphoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients completing two-thirds of their assigned treatment (time frame: 30 days after initiation of CAR-T therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2026.