Neurotoxicity Prophylaxis With Intrathecal Dexamethasone and Simvastatin Post Axi-Cel

  • STATUS
    Recruiting
  • End date
    Dec 2, 2023
  • participants needed
    20
  • sponsor
    Masonic Cancer Center, University of Minnesota
Updated on 2 September 2021
remission
lymphoma
cell transplantation
dexamethasone
chemotherapy regimen
follicular lymphoma
diffuse large b-cell lymphoma
b-cell lymphoma
large b-cell lymphoma
high dose chemotherapy

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.

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.

Details
Condition Lymphoproliferative Disorder, Non-Hodgkin's Lymphoma, Lymphoma, Lymphoproliferative disorders, lymphomas
Treatment Dexamethasone, Simvastatin
Clinical Study IdentifierNCT04514029
SponsorMasonic Cancer Center, University of Minnesota
Last Modified on2 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

- 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
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