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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
DOUBLE
Enrollment
12
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States
Johns Hopkins Oncology Center
Baltimore, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Absolute total CD4 cell counts
The primary treatment effect is defined as an absolute increase in CD4 counts in patients treated with glycosylated recombinant human interleukin-7 compared to the control group patients without glycosylated recombinant human interleukin-7 at week 6 after radiation treatment + temozolomide treatment.
Time frame: At 6 weeks (after standard radiation and temozolomide treatment completion)
Optimal dose of glycosylated recombinant human interleukin-7 determined by dose-limiting toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
The optimal dose will be selected based on the highest absolute increase of CD4 counts compared to the control if toxicity profiles are similar between the two dose levels. Otherwise, safety will be the first consideration for dose selection. The results of the two concurrent dexamethasone groups will be summarized with standard descriptive statistics. The dose selection criteria will be similar to the non-dexamethasone groups with priority on safety rather than the highest absolute increase of CD4 counts.
Time frame: 4 weeks
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Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States
Washington University
St Louis, Missouri, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
Abrams Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States