rhIL-7-hyFc for Brain Tumor

Not currently recruiting at 1 trial location

Overseen By Milan Chheda, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Washington University School of Medicine

Must be taking: Radiation, Temozolomide

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Active viral infection, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called rhIL-7-hyFc (also known as Efineptakin alfa, NT-I7, Hyleukin-7, or GX-I7) to determine if it can help patients with high-grade glioma (a type of brain tumor) by increasing their lymphocyte counts, which are crucial for a healthy immune system. The first part of the trial assesses the treatment's safety, while the second part compares its effects with a placebo (a harmless, inactive substance) in patients also receiving standard treatments like radiation and chemotherapy. Candidates for this trial have high-grade gliomas and are undergoing radiation and temozolomide treatment. As a Phase 1, Phase 2 trial, this study aims to understand how the treatment works in people and measure its effectiveness in an initial group, offering patients a chance to contribute to groundbreaking research.

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on other investigational drugs that affect lymphocyte counts or if you have an active viral infection requiring treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that rhIL-7-hyFc is generally safe for humans. One study found it safe and effective for patients with high-grade glioma, a type of brain cancer, who were also receiving standard treatments like temozolomide. Another study found that GX-I7, another name for rhIL-7-hyFc, safely boosts T cells, which are crucial for the immune system.

Further research indicates that NT-I7, a similar treatment, was safe and well-tolerated in patients with high-grade glioma. These patients experienced an increase in lymphocytes, a type of white blood cell that helps fight infections. Overall, these findings suggest that rhIL-7-hyFc is well-tolerated and can be safely administered to patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain tumors?

Researchers are excited about rhIL-7-hyFc for treating brain tumors because it introduces a fresh approach to boosting the immune system. Unlike standard treatments like radiation and chemotherapy, which directly target tumor cells, rhIL-7-hyFc works by enhancing the body's immune response. This drug acts on T-cells, potentially improving the immune system's ability to fight cancer alongside existing therapies. Additionally, rhIL-7-hyFc is administered via simple intramuscular injections, which could make it more convenient for patients compared to more invasive treatment methods.

What evidence suggests that rhIL-7-hyFc might be an effective treatment for high grade glioma?

Research has shown that rhIL-7-hyFc, which participants in this trial may receive, can strengthen the immune system in people with brain tumors, such as high-grade gliomas. Studies indicate that this treatment increases lymphocytes, which are crucial for fighting cancer. Specifically, rhIL-7-hyFc boosts CD4 lymphocytes, vital for protecting the body against diseases. Animal studies suggest that this treatment can improve the area around the tumor, enhancing the effectiveness of other cancer treatments. Overall, early results are promising and suggest that rhIL-7-hyFc could enhance the body's defense against brain tumors. ^{2 3 4 6 7}

Who Is on the Research Team?

Milan Chheda, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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.

My glioblastoma is IDH1 wildtype and MGMT promoter unmethylated.

I've had surgery for my tumor, followed by radiation and TMZ treatment. I may have used Gliadel Wafers, glucocorticoids, or a TTF device.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Temozolomide Treatment

Participants receive concurrent radiation therapy and temozolomide as part of the standard treatment

6 cycles of 28 days each

Regular visits as per treatment protocol

rhIL-7-hyFc Administration

Participants receive rhIL-7-hyFc or placebo injections at specified intervals after radiation and temozolomide treatment

37 weeks

4 injections at specified intervals

Follow-up

Participants are monitored for safety, effectiveness, and progression-free survival

5 years and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• rhIL-7-hyFc

Trial Overview 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.

How Is the Trial Designed?

Group I: Randomized Phase II: rhIL-7-hyFc Experimental Treatment 3 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: Placebo Experimental Treatment 3 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-hyFc Experimental Treatment 3 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-hyFc Dose Level 6 (960 mcg/kg) Experimental Treatment 3 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

Group V: Phase I: rhIL-7-hyFc Dose Level 5 (720 mcg/kg) Experimental Treatment 3 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

Group VI: Phase I: rhIL-7-hyFc Dose Level 4 (540 mcg/kg) Experimental Treatment 3 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

Group VII: Phase I: rhIL-7-hyFc Dose Level 3 (240 mcg/kg) Experimental Treatment 3 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

Group VIII: Phase I: rhIL-7-hyFc Dose Level 2 (120 mcg/kg) Experimental Treatment 3 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

Group IX: Phase I: rhIL-7-hyFc Dose Level 1 (60 mcg/kg) Experimental Treatment 3 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

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

The Foundation for Barnes-Jewish Hospital

Collaborator

Trials

43

Recruited

6,600+

NeoImmuneTech

Industry Sponsor

Trials

16

Recruited

780+

Published Research Related to This Trial

The study of hIL-7-hyFc, involving 30 healthy volunteers, demonstrated that this treatment significantly increased lymphocyte counts, particularly T-cells, with effects peaking three weeks post-administration and lasting for several weeks.

hIL-7-hyFc was well-tolerated with minimal side effects, primarily injection site reactions that resolved on their own, suggesting it could be a safe and effective option for patients with weakened T-cell immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

hIL-7-hyFc, A Long-Acting IL-7, Increased Absolute Lymphocyte Count in Healthy Subjects. Lee, SW., Choi, D., Heo, M., et al.[2021]

Recombinant human interleukin 4 (rhIL-4) demonstrated an antiproliferative effect on five out of nine human tumor cell lines, indicating its potential as a therapeutic agent in cancer treatment.

In animal studies, rhIL-4 treatment significantly inhibited the growth of xenotransplanted tumors in mice, suggesting that rhIL-4 may directly affect tumor growth without causing significant immune cell infiltration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human interleukin 4 has antiproliferative activity on human tumor cell lines derived from epithelial and nonepithelial histologies. Topp, MS., Papadimitriou, CA., Eitelbach, F., et al.[2006]

In a study involving 18 patients with recurrent glioblastoma, treatment with a long-acting engineered version of interleukin-7 (rhIL-7-hyFc) significantly increased total lymphocyte count (TLC) from an average of 1131 cells/mm3 to 4356 cells/mm3, indicating its efficacy in restoring immune function.

The treatment was well-tolerated, showing no serious toxicity, and resulted in a median overall survival of 378 days and progression-free survival of 231 days, suggesting potential benefits when combined with various chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compassionate use of recombinant human IL-7-hyFc as a salvage treatment for restoring lymphopenia in patients with recurrent glioblastoma. Ahn, S., Park, JS., Kim, H., et al.[2023]

Recombinant human interleukin-12 (rhIL-12) significantly reduced the drop in peripheral blood cell counts and improved immune function in patients undergoing high-dose radiotherapy, based on a study of 100 subjects.

While rhIL-12 showed effective therapeutic benefits, some patients experienced mild side effects, such as low fever and liver function impairment, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of recombinant human interleukin-12 for treatment of complications after radiotherapy for tumor patients. Guo, N., Wang, WQ., Gong, XJ., et al.[2020]

The study involving 30 healthy Chinese subjects demonstrated that GR007, a recombinant human interleukin-1 receptor antagonist, was safe and well-tolerated, with no serious adverse events reported and no dose-dependent adverse effects observed.

Pharmacokinetic analysis indicated that GR007 has a median time to maximum concentration of 2.75 to 4.00 hours and a dose-proportional increase in the area under the concentration vs time curve, supporting its potential for use in ongoing clinical trials for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety of Recombinant Human Interleukin-1 Receptor Antagonist GR007 in Healthy Chinese Subjects. Xie, R., Zhang, Y., Zhao, N., et al.[2020]

The combination of recombinant human interleukin-1 alpha (rHIL-1 alpha) or recombinant murine interferon-beta (rIFN-beta) with recombinant human interleukin-2 (rHIL-2) significantly enhances the antitumor activity against adenocarcinoma 755, especially when administered in divided doses.

In contrast, this combination therapy showed only marginal effectiveness against Lewis lung carcinoma, indicating that some tumors may be resistant to cytokine treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Iigo, M., Nishikata, K., Hoshi, A.[2006]

A study of 38 patients with high-grade gliomas revealed that the majority expressed the epidermal growth factor receptor (EGFR) and interleukin-13 receptor (IL13R), suggesting that targeting these receptors with fusion proteins could be effective in treatment.

The safety profile of EGFR-targeted fusion proteins may be better than those targeting other receptors like IL4R or transferrin receptor (TfR), indicating a potential advantage in choosing the right therapeutic approach based on receptor expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth factor receptor expression varies among high-grade gliomas and normal brain: epidermal growth factor receptor has excellent properties for interstitial fusion protein therapy. Liu, TF., Tatter, SB., Willingham, MC., et al.[2022]

The hybrid Fc-fused long-acting recombinant human IL-7 (rhIL-7-hyFc) significantly enhances the antitumor response by expanding CD8+ T cells in the tumor microenvironment, leading to increased tumor-reactive T cells with improved effector functions.

When combined with chemotherapy and checkpoint inhibitors, rhIL-7-hyFc not only boosts the antitumor response but also restores CD8+ T cell levels even in conditions of low T lymphocyte counts, suggesting its potential as an effective immunotherapy strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy. Kim, JH., Kim, YM., Choi, D., et al.[2022]

In a study involving 7-day-old rats subjected to brain hypoxia-ischemia, the administration of the interleukin-1 antagonist rhIL-1ra significantly reduced brain injury, indicating its strong neuroprotective effects.

The treatment with rhIL-1ra, given before and/or after the hypoxic exposure, suggests its potential clinical utility in protecting against brain damage caused by hypoxia-ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The interleukin-1 receptor antagonist (rhIL-1ra) protects against cerebral infarction in a rat model of hypoxia-ischemia. Martin, D., Chinookoswong, N., Miller, G.[2022]

In a study of 391 patients with ischaemic stroke, the IL1RN gene polymorphism did not affect the severity of stroke symptoms at their worst, but those homozygous for the IL1RN*2 allele experienced less severe neurological and functional impairments over time (from 7 days to 1 year).

However, patients with at least one IL1RN*2 allele had a higher risk of death in the first week, and those homozygous for this allele faced an increased risk of death within the first month, suggesting that this genetic variation may influence both stroke outcomes and the effectiveness of treatments like rhIL1ra.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL1RN intron 2 polymorphism caused by variable number tandem repeats is associated with 1-year outcome in patients with ischaemic stroke. Gromadzka, G., Sarzynska-Dlugosz, I., Czlonkowska, A.[2018]

In a study involving 27 children with solid tumors, the maximum tolerated dose (MTD) of recombinant human interleukin-1 alpha (rhuIL-1 alpha) was determined to be 3 micrograms/m2/day, with side effects including fever, chills, headache, and hypotension.

Despite being safe for use in children undergoing intensive chemotherapy, rhuIL-1 alpha did not demonstrate any significant hematoprotective effects against chemotherapy-induced blood toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of subcutaneous interleukin-1 alpha in children with malignant solid tumors. Furman, WL., Luo, X., Fairclough, D., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12356974/

GX-I7, a long-acting IL-7, safely and effectively increased ... In vivo, GX-I7 led to an increase in peripheral lymphocyte counts and TILs when administered either in monotherapy or combination therapy with cyclophosphamide ...

2. academic.oup.com academic.oup.com/neuro-oncology/article-abstract/26/Supplement_8/viii90/7890167

CTIM-24. PHASE II TRIAL OF RHIL-7-HYFC IN PATIENTS ... rhIL-7-hyFc is safe and effective in improving ALC and CD4 ... Brain Tumors: Findings from a Multisite, Prospective, Longitudinal Trial.

3. medrxiv.org medrxiv.org/content/10.1101/2024.02.12.23299638v1.full.pdf

GX-I7(rhIL-7-hyFc, efineptakin alfa), a long-acting IL-7, ... In animal studies, GX-I7 showed promising results by ... induces an inflamed tumor microenvironment and improves the efficacy of cancer.

4. withpower.com withpower.com/trial/phase-2-glioma-2019-dc916

rhIL-7-hyFc for Brain Tumor · Info for Participants 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 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38471713/

rhIL-7-hyFc and hIL-2/TCB2c combination promotes an ... Our data demonstrate that the combination of rhIL-7-hyFc and hIL-2/TCB2c increases efficacy and generates an immune-stimulatory tumor microenvironment (TME).

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS2085

Efficacy and safety study of neoadjuvant efineptakin alfa ... Our preliminary data suggests that combining NT-I7 with pembrolizumab, an anti-PD-1 antibody, improves survival in murine glioma models. The ...

7. academic.oup.com academic.oup.com/noa/article/8158267

Phase I study of NT-I7, a long-acting interleukin-7, in severe ... NT-I7 was safe, well tolerated in high grade glioma patients with treatment-related lymphopenia. NT-I7 increased absolute lymphocyte count and ...