Trial Summary
What is the purpose of this trial?The investigators have developed a phase I/II clinical trial to evaluate the effect of rhIL-7-hyFc on lymphocyte counts in patients with high grade glioma (HGG).
A phase I study will test whether rhIL-7-hyFc can be safely administered to patients with HGG. Six doses of rhIL-7-hyFc will be tested using a mix of Accelerated Phase and standard 3+3 dose-escalation design. The phase II portion to test effect of rhIL-7-hyFc on lymphocyte counts will use placebo-controlled randomization in HGG patients whose treatment include the standard radiation therapy (RT) and temozolomide (TMZ).
Do I have to stop taking my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents that affect lymphocyte counts, and you should not have an active viral infection or active autoimmune disease requiring systemic treatment. Glucocorticoid therapy and certain replacement therapies are allowed.
What data supports the idea that rhIL-7-hyFc for Brain Tumor is an effective treatment?
The available research shows that rhIL-7-hyFc can help improve the immune response in patients with brain tumors like glioblastoma. One study highlights its use in patients with recurrent glioblastoma, where it was used to address low levels of immune cells, which is a common issue in cancer patients. By increasing the number of these immune cells, rhIL-7-hyFc may help the body fight the tumor more effectively. This suggests that rhIL-7-hyFc could be a promising option for enhancing the body's natural defenses against brain tumors.
12345What safety data exists for rhIL-7-hyFc (Efineptakin alfa, NT-I7, Hyleukin-7, GX-I7)?
The provided research does not contain safety data for rhIL-7-hyFc or its other names (Efineptakin alfa, NT-I7, Hyleukin-7, GX-I7). The studies focus on different interleukin agents, such as rhIL-1ra and rhIL-1 alpha, which are unrelated to rhIL-7-hyFc.
56789Is rhIL-7-hyFc a promising drug for brain tumors?
Yes, rhIL-7-hyFc is a promising drug for brain tumors because it helps boost the immune system by increasing the number of lymphocytes, which are important cells that fight cancer. It creates a more active environment around the tumor, making other cancer treatments more effective.
1231011Eligibility Criteria
This trial is for adults with certain high-grade brain tumors (gliomas) that need radiation and Temozolomide treatment. Participants must have adequate organ function, not be pregnant, agree to use contraception, and can't have active infections or autoimmune diseases requiring systemic treatment.Inclusion Criteria
I have a high-grade brain tumor that needs radiation and TMZ treatment.
Adequate organ and marrow function: Absolute neutrophil count ≥ 1,000/mcL, Platelets ≥ 75,000/mcL, Hemoglobin ≥ 8 g/dL, Total bilirubin ≤ 3.0 x institutional upper limit of normal, AST (SGOT)/ALT (SGPT) ≤ 3.0 × institutional upper limit of normal, Absolute lymphocyte count (ALC) ≥ 600/mcL (required for phase I and randomized phase II only), Karnofsky Performance Status (KPS) ≥ 60%, Able to provide written informed consent, Women of childbearing potential must have a negative serum pregnancy test prior to study entry (within 14 days). Patients must be willing to be on adequate contraception during treatment, 18 years of age
My glioblastoma is IDH1 wildtype and MGMT promoter unmethylated.
+1 more
Exclusion Criteria
My heart screening tests showed significant findings.
I have not received a live vaccine in the last 30 days.
I am currently on medication for a viral infection.
+4 more
Participant Groups
The study evaluates rhIL-7-hyFc's safety and its effect on lymphocyte counts in patients with high-grade gliomas undergoing standard treatments. It includes a phase I dose-escalation part followed by a phase II placebo-controlled comparison alongside radiation therapy and Temozolomide.
4Treatment groups
Experimental Treatment
Group I: Randomized Phase II: rhIL-7-hyFcExperimental Treatment4 Interventions
Per standard treatment, patients will receive concurrent RT/TMZ followed by adjuvant TMZ on Days 1-5 of a 28-day cycle for a total of 6 cycles. rhIL-7hyFc will be given by intramuscular injection starting at the end of RT/TMZ (within 14 days after last day of RT/TMZ). The 2nd injection will be administered 3-5 days after the last dose of cycle 3 TMZ treatment (\~week 13). The 3rd injection will be given 3-5 days after the last dose of cycle 6 TMZ treatment (\~week 25). Note the 2nd and 3rd injections should be administered once between Day 3 through 5 following the last dose of TMZ to achieve the strongest response. The 4th injection (last injection in the study) will be given after completion of monthly TMZ (\~Week 37). A total of 4 doses of rhIL-7-hyFc injections are planned.
Group II: Randomized Phase II: PlaceboExperimental Treatment4 Interventions
-Per standard treatment, patients will receive concurrent RT/TMZ followed by adjuvant TMZ on Days 1-5 of a 28-day cycle for a total of 6 cycles. Placebo will be given by intramuscular injection starting at the end of RT/TMZ (within 14 days after last day of RT/TMZ). The 2nd injection will be administered 3-5 days after the last dose of cycle 3 TMZ treatment (\~week 13). The 3rd injection will be given 3-5 days after the last dose of cycle 6 TMZ treatment (\~week 25). Note the 2nd and 3rd injections should be administered once between Day 3 through 5 following the last dose of TMZ to achieve the strongest response. The 4th injection (last injection in the study) will be given after completion of monthly TMZ (\~Week 37). A total of 4 doses of placebo injections are planned.
Group III: Phase II Expansion Arm: rhIL-7-hyFcExperimental Treatment3 Interventions
Per standard treatment, patients will receive concurrent RT/TMZ followed by adjuvant TMZ on Days 1-5 of a 28-day cycle for a total of 6 cycles. rhIL-7hyFc will be given by intramuscular injection starting at the end of RT/TMZ (within 14 days after last day of RT/TMZ). The 2nd injection will be administered 3-5 days after the last dose of cycle 3 TMZ treatment (\~week 13). The 3rd injection will be given 3-5 days after the last dose of cycle 6 TMZ treatment (\~week 25). Note the 2nd and 3rd injections should be administered once between Day 3 through 5 following the last dose of TMZ to achieve the strongest response. The 4th injection (last injection in the study) will be given after completion of monthly TMZ (\~Week 37). A total of 4 doses of rhIL-7-hyFc injections are planned.
Group IV: Phase I: rhIL-7-hyFcExperimental Treatment4 Interventions
* Per standard treatment, patients will receive concurrent RT/TMZ followed by adjuvant TMZ on Days 1-5 of a 28-day cycle for a total of 6 cycles. rhIL-7hyFc will be given by intramuscular injection starting at the end of RT/TMZ (within 7 days after last day of RT/TMZ). The 2nd injection will be administered 3-5 days after the last dose of cycle 3 TMZ treatment (\~week 13). The 3rd injection will be given 3-5 days after the last dose of cycle 6 TMZ treatment (\~week 25). Note the 2nd and 3rd injections should be administered once between Day 3 through 5 following the last dose of TMZ to achieve the strongest response. The 4th injection (last injection in the study) will be given after completion of monthly TMZ (\~Week 37). A total of 4 doses of rhIL-7-hyFc injections are planned
* The phase I part will begin with an Accelerated Phase with 1 patient per cohort at the first 2 doses (60 mcg/kg and 120 mcg/kg) followed by a standard 3+3 design on the remaining 4 dose levels
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Washington University School of MedicineSaint Louis, MO
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Who Is Running the Clinical Trial?
Washington University School of MedicineLead Sponsor
The Foundation for Barnes-Jewish HospitalCollaborator
NeoImmuneTechIndustry Sponsor
References
Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy. [2022]Label="OBJECTIVES" NlmCategory="OBJECTIVE">Emerging oncotherapeutic strategies require the induction of an immunostimulatory tumor microenvironment (TME) containing numerous tumor-reactive CD8+ T cells. Interleukin-7 (IL-7), a T-cell homeostatic cytokine, induces an antitumor response; however, the detailed mechanisms underlying the contributions of the IL-7 to TME remain unclear. Here, we aimed to investigate the mechanism underlying the induction of antitumor response by hybrid Fc-fused long-acting recombinant human IL-7 (rhIL-7-hyFc) through regulation of both adaptive and innate immune cells in the TME.
Compassionate use of recombinant human IL-7-hyFc as a salvage treatment for restoring lymphopenia in patients with recurrent glioblastoma. [2023]Addressing lymphopenia in cancer patients has been suggested as a novel immunotherapeutic strategy. As interleukin-7 (IL-7) is necessary for proliferation of lymphocytes and to increase total lymphocyte count (TLC), IL-7 therapy has been attempted in various cancers. Here, we describe the clinical results of treatment of recurrent glioblastoma (GBM) with a long-acting engineered version of recombinant human IL-7 (rhIL-7-hyFc).
Effect of recombinant interleukin-1 alpha, recombinant interleukin-2, recombinant interferon-beta, and recombinant tumor necrosis factor on subcutaneously implanted adenocarcinoma 755 and Lewis lung carcinoma. [2006]The antitumor activity of recombinant human interleukin-1 alpha (rHIL-1 alpha), recombinant human tumor necrosis factor, and recombinant murine interferon-beta (rIFN-beta) was augmented by concomitant administration of recombinant human interleukin-2 (rHIL-2) in the treatment of adenocarcinoma 755. Especially when a divided dose (two doses/day) of rHIL-1 alpha or rIFN-beta was combined with a divided dose of rHIL-2, the antitumor effect was markedly potentiated. However, only a marginal effect was seen by combination of rHIL-1 alpha and/or rIFN-beta and rHIL-2 against Lewis lung carcinoma, a tumor that is resistant to cytokines.
Growth factor receptor expression varies among high-grade gliomas and normal brain: epidermal growth factor receptor has excellent properties for interstitial fusion protein therapy. [2022]Convection-enhanced delivery of fusion proteins is a novel therapeutic approach for patients with relapsed or refractory high-grade gliomas. Multiple different fusion proteins have been produced that target different receptors on brain tumor cells. The sensitivity of different gliomas to fusion proteins has been shown to depend in part on the expression of the target receptor. We undertook a comparative study of the presence of the epidermal growth factor receptor (EGFR), interleukin-13 receptor (IL13R), interleukin-4 receptor (IL4R), and transferrin receptor (TfR) determined by immunofluorescence microscopy among fresh frozen tumor samples from 38 patients with high-grade gliomas (glioblastoma multiforme or anaplastic astrocytoma). The frequency of high receptor expression was 32 of 38 (84%) for EGFR, 30 of 38 (79%) for IL13R, 25 of 38 (66%) for TfR, and 17 of 38 (45%) for IL4R. Reactivity of normal brain endothelium was observed for TfR, and reactivity of normal brain astrocytes was observed for IL4R. Because of cross-reactivity of interleukin-13 with the IL4R-IL13Ralpha1 receptor, we infer reactivity of interleukin-13 with normal astrocytes. In contrast, EGFR was not observed in normal brain. A number of patients (10 of 38 patients) showed unequal expression of EGFR and IL13R. Thus, some patients may benefit more from interstitial therapy with an EGFR-directed fusion protein than from therapy with an IL13R-directed fusion protein and vice versa. The safety profile may be improved with an agent directed to EGFR versus agents directed to TfR, IL4R, or IL13R. Design of clinical trials of fusion proteins in patients with brain tumors may be enhanced by inclusion of relevant receptor density measurements.
Study of recombinant human interleukin-12 for treatment of complications after radiotherapy for tumor patients. [2020]Label="AIM" NlmCategory="OBJECTIVE">To evaluate the treatment effects of recombinant human interleukin-12 (rhIL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.
The interleukin-1 receptor antagonist (rhIL-1ra) protects against cerebral infarction in a rat model of hypoxia-ischemia. [2022]We assessed the cerebral protective effects of the competitive interleukin-1 antagonist rhIL-1ra in 7-day-old rats that were subjected to brain hypoxia-ischemia by unilateral carotid artery ligation and subsequent exposure to 2 h of 7.5% O2-balanced N2. This procedure leads to atrophy in the cerebral hemisphere ipsilateral to carotid occlusion, with prominent foci of neuronal infarction in the striatum. Systemic administration of 100 mg/kg of rhIL-1ra before and/or after the hypoxic exposure limited the insult. The results indicate that rhIL-1ra has potent neuroprotective properties against morphologic brain injury from hypoxia-ischemia. rhIL-1ra may prove to be clinically useful in protecting against hypoxia-ischemia-related disorders.
IL1RN intron 2 polymorphism caused by variable number tandem repeats is associated with 1-year outcome in patients with ischaemic stroke. [2018]Results of experimental and clinical studies suggest that recombinant human interleukin 1 receptor antagonist (rhIL1ra) may be a good new therapeutic agent for acute stroke. In humans, IL1ra is encoded by the IL1RN gene located on chromosome 2.
Pharmacokinetics and Safety of Recombinant Human Interleukin-1 Receptor Antagonist GR007 in Healthy Chinese Subjects. [2020]The recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) GR007 is a candidate drug with the potential to prevent the toxicity induced by chemotherapy agents by blocking the IL-1 signaling pathway. The aim of this study was to assess the pharmacokinetics and safety of GR007 in healthy Chinese subjects.
Phase I trial of subcutaneous interleukin-1 alpha in children with malignant solid tumors. [2019]Interleukin-1 alpha (IL-1 alpha) is myeloprotective in a variety of animal models of cancer chemotherapy and is similarly beneficial in adults treated with carboplatin, 5-fluorouracil, and after autologous bone marrow transplantation. There are no trials of this agent in children. Our purpose was to determine the toxicity and maximum tolerated dose (MTD) of recombinant human interleukin-1 alpha (rhuIL-1 alpha) in children with solid tumors receiving intensive cancer chemotherapy and to evaluate its myelo-protective effects. Cohorts of patients received rhuIL-1 alpha in doses of 0.1-10 micrograms/m2 for 4 days by subcutaneous injection prior to ICF chemotherapy (ifosfamide, 2 g/m2/day x 3, carboplatin targeted to an area under the curve of 8 mg/ml x min on day 1, and etoposide, 100 mg/m2 daily for 3 days). Patients were randomized to receive rhuIL-1 alpha before either the first or second course of therapy. After the MTD of rhuIL-1 alpha was determined an additional group of patients received rhuIL-1 alpha at the dose immediately following ICE chemotherapy. The dose-limiting toxicities of rhuIL-1 alpha in the 27 children tested comprised systemic symptoms of fever, chills, headache, and hypotension. The MTD was 3 micrograms/m2/day. There were no differences in chemotherapy-induced hematologic toxicity with increasing doses of rhuIL-1 alpha or in comparisons before or after ICE chemotherapy. Although rhuIL-1 alpha can be given safely to children receiving myelosuppressive chemotherapy, clinical usefulness would mandate a significant hematopoietic benefit in view of the trouble some side effects identified. We saw no evidence of a hematoprotective effect.
hIL-7-hyFc, A Long-Acting IL-7, Increased Absolute Lymphocyte Count in Healthy Subjects. [2021]A low lymphocyte count puts immune-compromised patients at risk of mortality. hIL-7-hyFc is a homodimeric interleukin-7 (IL-7), a potent T-cell amplifier, fused to the hybridizing IgD/IgG4 immunoglobulin domain. We performed a randomized, double-blind, placebo-controlled, dose-escalation, phase I study to assess the pharmacokinetic, pharmacodynamic, safety, tolerability, and immunogenicity profiles of hIL-7-hyFc administered s.c. and i.m. to healthy volunteers. Thirty subjects randomly received hIL-7-hyFc or its matching placebo in an 8:2 ratio at 20, 60 μg/kg s.c., or 60 μg/kg i.m. The hIL-7-hyFc was slowly absorbed and its terminal half-life was 63.26 hours after i.m. administration. The hIL-7-hyFc increased absolute lymphocyte count, mostly in T-cells, which peaked 3 weeks after administration and then lasted for several additional weeks. The hIL-7-hyFc was well-tolerated after a single s.c. and i.m. administration. Injection site reaction was the most common treatment-emergent adverse event, which resolved spontaneously without treatment. The hIL-7-hyFc can be developed into a beneficial treatment option for patients with compromised T-cell immunity. This trial was registered at www.clinicaltrials.gov as #NCT02860715.
Recombinant human interleukin 4 has antiproliferative activity on human tumor cell lines derived from epithelial and nonepithelial histologies. [2006]Interleukin 4, a T cell-derived 20-kDa glycoprotein, plays an important role in regulating the immune response of B cells, T cells, and macrophages against infections and malignant cells. For this reason recombinant human interleukin 4 (rhIL-4) has entered early clinical trials in cancer patients. In the present study we report that rhIL-4 has an antiproliferative effect on five of nine cell lines derived from human colon tumors, head and neck tumors, and glioblastomas as measured by a decrease of colony formation in human tumor cloning assays. All of the cell lines with in vitro responsiveness express at least 100 high-affinity receptors for human interleukin 4 per cell on their cell surface, whereas the nonresponsive tumor cell lines lack expression of high-affinity receptors for human interleukin 4 on their cell surface. In the next series of experiments we have xenotransplanted some of the responsive cell lines into athymic nude mice. Subsequently, the animals were treated s.c. twice daily with 0.5 mg/m2 rhIL-4 or control vehicle for at least 12 days. There was a clear growth inhibition of these xenotransplanted tumors in the mice treated with rhIL-4. Histology of the tumors in both groups revealed no marked infiltration with murine hematopoietic and lymphocytic cells as evaluated by staining with a rat anti-mouse CD45 antibody. We conclude that rhIL-4 has a direct therapeutic activity on the growth of some human epithelial and nonepithelial tumor cell lines which, along with its regulatory function on hematolymphopoietic cells, makes this cytokine an interesting candidate for experimental tumor therapy.