study of the effect nt-i7 on cd4 counts in patients with high grade gliomas

Conditions: Lymphopenia; Malignant Glioma

Summary: the purpose of this study is to determine the maximum tolerated dose (mtd) and select optimal biological doses (obd) of the study drug nt-i7 in high grade glioma patients with severe lymphopenia, as well as to test the effect of nt-i7 on the cd4 counts of patients in comparison to control participants. this study has both a phase i and pilot component.

primary objectives: phase i: to determine the mtd (maximum tolerated dose) and select optimal biological doses (obd) of nt-i7 in hgg patients with severe lymphopenia pilot study: to test the effect of nt-i7 on cd4 counts compared to control secondary objectives: 1. to evaluate the optimal biological dose of nt-i7 2. to evaluate the effect of concurrent dexamethasone 3. to evaluate the duration of effect on cd4 counts (up to 6 months) 4. to evaluate the total lymphocyte counts over time and serial t cell lymphocyte subtypes and the effect on t cell repertoire (up to 6 months) 5. to evaluate the serial cytokine levels (up to 6 months) 6. to evaluate the impact of adjuvant temozolomide on nt-i7 effects on cd4 counts 7. to evaluate anti-drug antibodies 8. to evaluate the pharmacokinetic profile of nt-i7 after intramuscular administration in this patient population 9. to evaluate the safety and toxicity of nt-i7 in patients with high grade glioma outline: patients are assigned to 1 of 2 groups depending on their use of dexamethasone. group a: patients not on dexamethasone (or equivalent of an alternative corticosteroid), or on a dose lower than a physiologic dose (=\< 0.75 mg daily) group b: patients who require dexamethasone (or equivalent of an alternative corticosteroid) =\> 4 mg daily patients must have been on the group assignment dose of corticosteroids for at least 5 days prior to the dose of nt-i7. corticosteroid dose changes prior to the start of treatment are allowed as long as they do not alter patient's group assignment. phase i treatment plan all patients (both groups a and b) will be given a single dose of nt-i7 by intramuscular injection starting at 60 μg/kg, within one week after completing concurrent rt+tmz and before starting adjuvant tmz treatment, during the standard post-radiation break. following this period, as per standard treatment, patients will go on to receive adjuvant temozolomide on days 1-5 of 28-day cycles for 6 cycles. there should be about six weeks between the study injection and the start of adjuvant temozolomide; thus the start of adjuvant tmz will be approximately two weeks later than the usual start, which is 4 weeks post-end of radiation. patients who are delayed from receiving or are not able to receive adjuvant tmz treatment may continue on study; adjuvant tmz treatment is not a requirement for participation. pilot study treatment plan group a: participants will be given either a placebo (nt-i7 diluent) or one dose of nt-i7 at the phase i group a obd by intramuscular injection within one week after completing concurrent rt+tmz and before starting adjuvant tmz treatment, during the standard post-radiation break. group b: participants will be given one dose of nt-i7 at the phase i group b obd by intramuscular injection within one week after completing concurrent rt+tmz and before starting adjuvant tmz treatment, during the standard post-radiation break. after completion of study treatment, patients are followed up every 2 months for 2 years and then every 6 months thereafter.

Eligibility criteria:
inclusion criteria: * patients must have histologically confirmed high grade glioma by pathology (world health organization \[who\] grade iii and iv) * patients' post-operative treatment must have included at least 80% of standard radiation and concomitant temozolomide; patients may not have received any other prior chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor infiltrating lymphocytes \[til\], lymphokine-activated killer \[lak\] or gene therapy), or hormonal therapy for their brain tumor; prior gliadel wafers are allowed; glucocorticoid therapy is allowed * patients must have cd4 =\< 300 cells/mm\^3 in the last week (7 days) of standard radiation + temozolomide treatment (58-60 gy radiation with temozolomide 75 mg/m2 daily during radiation) * absolute neutrophil count \>= 1,000/mcl * platelets \>= 50,000/mcl (need to confirm before administering study drug) * hemoglobin \>= 9 g/dl * total bilirubin =\< institutional upper limit of normal * aspartate aminotransferase (ast) (serum glutamic oxaloacetic transaminase \[sgot\])/alanine aminotransferase (alt) (serum glutamate pyruvate transaminase \[sgpt\]) =\< 2.5 x institutional upper limit of normal * creatinine =\ = 60 ml/min/1.73 m\^2 for patients with creatinine levels above institutional normal * activated partial thromboplastin time (aptt) or partial thromboplastin time (ptt) =\< 1.5 x institutional upper limit of normal * patients must have a karnofsky performance status (kps) \>= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others) * patients must be able to provide written informed consent * women of childbearing potential must have a negative serum pregnancy test prior to study entry; women of childbearing potential and men must agree to use two birth control methods (either two barrier methods or a barrier method plus a hormonal method) or abstinence prior to study entry and for the duration of study participation (through at least 90 days after the last study injection); should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * dexamethasone dose must be provided for treatment group assignment: * group a: patients not on dexamethasone or on a dose =\< 0.75 mg daily (or equivalent of an alternative corticosteroid) * group b: patients who require dexamethasone \>= 4 mg daily (or equivalent of an alternative corticosteroid) \*\* patients must have been on the group assignment dose of corticosteroids for at least 5 days prior to the dose of nt-i7; corticosteroid dose changes prior to the start of treatment are allowed as long as they do not alter patient's group assignment exclusion criteria * patients receiving any other investigational agents are ineligible * patients with known hypersensitivity to nt-i7 or any component used in the vehicle/formulation are ineligible * patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible * pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with nt-i7 * patients with human immunodeficiency virus (hiv) are excluded * patients with a known or screening-period-determined corrected qt (qtc) interval \> 450 msec and patients who require a therapy with a drug known to prolong the qt/qtc interval, are ineligible * patients with a history of or who currently have evidence of autoimmune disease (other than autoimmune thyroid disease managed with thyroid hormone replacement or vitiligo) including: myasthenia gravis, guillain barre syndrome, systemic lupus erythematosus, multiple sclerosis, scleroderma, ulcerative colitis, crohn's disease, autoimmune hepatitis, wegener's etc., are ineligible