A Safety Study of Fingolimod With Radiation and Temozolomide in Newly Diagnosed High Grade Glioma

• Status: Completed
• Trial end date: 2017-09-01
• Target enrollment: 0
• Participant gender: All

Summary

A recent prospective multicenter study by Dr. Grossman demonstrated that 40% of patients with high grade glioma undergoing radiation and chemotherapy developed severe and persistent lymphopenia (CD4 counts <200 cells/mm3). This lymphopenia lasted for twelve months following radiation treatment and on multivariate analysis was associated with shorter survival. Our group has data that strongly suggests that this lymphopenia is secondary to the inadvertent radiation of circulating lymphocytes as they pass through the radiation beam. Investigators propose the use of FDA approved for multiple sclerosis, fingolimod to signal lymphocytes to leave the circulation prior to the initiation of radiation. It is a functional antagonist of the sphingosine-1-phosphate receptor (S1PR) pathway and prevents lymphocyte egress from secondary lymphoid organs.

Oral fingolimod will be given 1 week prior to the initiation of concurrent radiation and temozolomide and will be discontinued immediately upon completion of the six weeks of therapy. The primary objective is to evaluate if fingolimod can be safely combined with radiation and temozolomide. Secondary endpoint is total lymphocyte counts (TLC) for the proposed study participants. Investigators expect that patients receiving radiation and temozolomide plus fingolimod have a recovery of lymphocyte counts to 80% of baseline within four months, reference to historical control in which sustained lymphopenia lasted for twelve months.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Treatments: Dacarbazine; Fingolimod Hydrochloride; Temozolomide

Criteria

Inclusion Criteria:

• Gender: Male and Female

• Age: Patients must be at least 18 years of age.

• Race: Minorities will be recruited. No exclusion to this study will be based on race.

• Patients must have histologically confirmed high grade astrocytoma, WHO grade III or IV, by pathology.

• Patients' proposed post-operative treatment plan must include standard focal brain irradiation and temozolomide.

• Patients must have a Karnofsky Performance Status > 60 % (i.e. the patient must be able to care for himself/herself with occasional help from others).

• Patients must have normal bone marrow function, with a baseline total lymphocyte count > 1000.

• Patients must be able to provide informed consent.

• Glucocorticoid use is allowed.

• Women of childbearing potential should use effective contraception during and for two months after stopping fingolimod.

Exclusion Criteria:

• Patients must not have received prior radiation therapy, chemotherapy, immunotherapy, therapy with biologic agents or hormonal therapy for their brain tumor.

• Patients must not have recent (within six months) occurrence of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III/IV heart failure.

• Patients must not have history of or presence of Mobitz Type II 2nd degree or 3rd degree atrioventricular block or sick sinus syndrome, unless patient has a pacemaker.

• Patients must not have baseline QTc interval > 500 ms.

• Patients must not be on treatment with Class Ia or Class III antiarrhythmic drugs.

• Patients must not have a history of macular edema, uveitis or diabetes mellitus.

• Patients must not have elevated liver transaminase levels. Adequate liver function is defined as total bilirubin < 1.5 times upper limit of normal, SGPT (ALT) < 5 times upper limit of normal and serum albumin > 2 g/dL.

• Patients must not have an active infection.

• Patients with known HIV will be excluded.

• Patients with collagen vascular disease are excluded.

• Patients taking immunosuppressive medications (other than dexamethasone) will be excluded.