Poly-ICLC for Low-Grade Glioma

(NF111 Trial)

No longer recruiting at 21 trial locations

Overseen By Karen A Cole-Plourde, BS

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Radiation treatment, Malignant glioma, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called poly-ICLC for children and young adults with neurofibromatosis type 1 (NF1) who have low-grade gliomas, a type of slow-growing brain tumor. The goal is to evaluate the treatment's effectiveness in shrinking tumors. Participants will receive poly-ICLC injections twice a week for about a year. Children and young adults with NF1 who have undergone previous treatment but still show tumor progression, such as worsening symptoms or tumor growth on MRI, might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot be on other anti-tumor or experimental therapies, and you should not be on high doses of steroids or immunosuppressive therapy.

Is there any evidence suggesting that poly-ICLC is likely to be safe for humans?

Research has shown that poly-ICLC is generally safe and well-tolerated. One study found that patients taking low doses of poly-ICLC over a long period did not experience major safety problems, suggesting that most people can handle the treatment well. Another study found that poly-ICLC was safe when combined with other treatments for patients with brain tumors. Overall, while some minor side effects might occur, the treatment appears safe for use in clinical settings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for low-grade glioma focus on traditional methods like surgery, radiation, and chemotherapy. But Poly-ICLC is different because it leverages the immune system to fight the tumor. This treatment uses an active ingredient called Poly-ICLC, which is an immune modulator that enhances the body's natural defenses against cancer cells. Unlike conventional treatments, which often come with severe side effects, Poly-ICLC is administered via a simple intramuscular injection, potentially offering a more tolerable option for patients. Researchers are excited about its ability to target the cancer in a novel way, providing hope for more effective and less invasive treatment options.

What evidence suggests that poly-ICLC might be an effective treatment for low-grade glioma?

Research has shown that poly-ICLC might help treat brain tumors like low-grade gliomas by boosting the immune system to fight tumor cells. Studies have found that poly-ICLC becomes more effective when combined with other treatments, such as vaccines or immune therapies, because it enhances their effects. However, past research with adults revealed that using poly-ICLC alone did not significantly improve outcomes for certain aggressive brain tumors like anaplastic gliomas. Its effectiveness may depend on the type of glioma and its combination with other treatments. In this trial, participants will receive poly-ICLC alone, which could be promising, especially when combined with other therapies in future studies. ^{2 3 4 6 7}

Who Is on the Research Team?

Juliette Southworth, BS, CCRP

Principal Investigator

University of Alabama at Birmingham, NFCTC

Are You a Good Fit for This Trial?

This trial is for pediatric patients under 22 years with Neurofibromatosis type 1 (NF1) and progressive low-grade gliomas. They must have had previous treatment, measurable tumor growth, and be in stable condition without recent surgeries or radiation therapy. Patients can't join if they've had certain other cancers, are pregnant/breastfeeding, on immunosuppressants, or unable to follow the study plan.

Inclusion Criteria

--- Hemoglobin: > 8.0 gm/dl (may transfuse PRBCs)

- Measurable Disease: Patients must have two-dimensional measurable tumor >1cm2.

My organs are functioning well.

Exclusion Criteria

Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 90 days after stopping study therapy are not eligible.

I do not have any severe illnesses that would stop me from safely receiving this treatment.

Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive poly-ICLC 20 mcg/kg/dose twice weekly for progressive low-grade gliomas

48 weeks

Twice weekly visits for dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Participants are monitored for progression free survival and toxicity

60 months

What Are the Treatments Tested in This Trial?

Interventions

• Poly ICLC

Trial Overview The trial tests poly-ICLC (Hiltonol®) for treating progressive low-grade brain tumors in children with NF1. It aims to see how well it works within the first year of treatment by measuring tumor response rates. The study will also explore secondary outcomes related to the drug's effects.

How Is the Trial Designed?

Group I: Administer Poly-ICLC Experimental Treatment 1 Intervention

Enrolled participants will receive poly-ICLC 20 mcg/kg/dose twice weekly IM (using Monday/Thursday or Tuesday/Friday schedule if possible).

Poly ICLC is already approved in United States for the following indications:

Approved in United States as Poly ICLC for:

• Adjuvant therapy for certain cancers

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Children's Healthcare of Atlanta

Collaborator

Trials

172

Recruited

108,000+

Children's Hospital Los Angeles

Collaborator

Trials

257

Recruited

5,075,000+

Published Research Related to This Trial

The IMA950 multipeptide vaccine, combined with the adjuvant poly-ICLC, was found to be safe and well tolerated in a study involving 19 glioma patients, with only four cases of temporary cerebral edema.

The vaccine successfully elicited CD8 T-cell responses in 63.2% of patients, with median overall survival for glioblastoma patients reaching 19 months, indicating promising immunogenicity and potential effectiveness in treating glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. Migliorini, D., Dutoit, V., Allard, M., et al.[2020]

The study demonstrated that a PLGA/PEG paste can effectively deliver temozolomide and etoposide directly into the cavity after surgical resection of high-grade gliomas, leading to a significant survival benefit in animal models.

In vivo results showed that over half of the treated animals were disease-free, indicating the potential of this delivery method to enhance the efficacy of chemotherapy when combined with adjuvant radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival in Malignant Glioma Is Significantly Prolonged by Neurosurgical Delivery of Etoposide and Temozolomide from a Thermo-Responsive Biodegradable Paste. Smith, SJ., Tyler, BM., Gould, T., et al.[2020]

Poly(I:C) and its derivative poly-ICLC have shown potential as effective immunotherapy agents for glioblastoma, demonstrating the ability to alter the immunological profile of glioblastoma cells and even kill them directly in preclinical models.

In clinical settings, poly-ICLC has been found to be safe and effective as an adjuvant therapy, particularly when combined with dendritic cell or peptide vaccines, suggesting it could enhance the overall effectiveness of glioblastoma treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review on poly(I:C) and poly-ICLC in glioblastoma: adjuvants coordinating the unlocking of immunotherapy. De Waele, J., Verhezen, T., van der Heijden, S., et al.[2021]

Local delivery of chemotherapy using drug-loaded polymer scaffolds can significantly reduce glioblastoma recurrence after surgical resection, with a novel biopolymer (Ace-DEX) showing superior results compared to a standard polyester (PLA).

In a study involving mice, those treated with Ace-DEX scaffolds had a 57% long-term survival rate at 120 days, while only 20% of those treated with PLA scaffolds survived, highlighting the importance of drug release rate in improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained Delivery of Doxorubicin via Acetalated Dextran Scaffold Prevents Glioblastoma Recurrence after Surgical Resection. Graham-Gurysh, E., Moore, KM., Satterlee, AB., et al.[2019]

In a phase II study involving 30 adults with glioblastoma, the combination of poly-ICLC and radiation therapy resulted in a 1-year survival rate of 69% and a median survival of 65 weeks, indicating a potential survival advantage over historical data without chemotherapy.

The treatment was relatively well-tolerated, but did not show a survival benefit compared to radiation therapy combined with other chemotherapy agents, suggesting that further research is needed to explore poly-ICLC's effectiveness in combination with standard treatments like temozolomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II clinical trial of poly-ICLC with radiation for adult patients with newly diagnosed supratentorial glioblastoma: a North American Brain Tumor Consortium (NABTC01-05). Butowski, N., Chang, SM., Junck, L., et al.[2022]

In a study involving 7 patients with malignant brain tumors, intravenous administration of Poly(ICLC) significantly induced serum interferon levels, with the highest titer reaching 875 reference units/ml, indicating a strong immune response.

The treatment was generally well-tolerated, with only mild side effects such as fever reported, while more serious side effects like hypotension and leukopenia occurred in a few cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I-II trials of poly(ICLC) in malignant brain tumor patients. Nakamura, O., Shitara, N., Matsutani, M., et al.[2020]

In a study involving tumor-bearing mice, the optimal therapeutic dose of poly(I,C)-LC (100 micrograms twice a week) not only enhanced immune response but also correlated with improved survival rates, indicating its efficacy in treating tumor ascites.

The study found that this optimal dosing schedule was less toxic compared to the maximum tolerated dose (50 micrograms daily), suggesting a safer approach to immunomodulation in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dissociation of therapeutic and toxic effects of polyinosinic-polycytidylic acid admixed with poly-L-lysine and solubilized with carboxymethyl cellulose in tumor-bearing mice. Hartmann, D., Adams, JS., Meeker, AK., et al.[2020]

Poly ICLC effectively induces high levels of serum interferon in both rodents and patients with malignant brain tumors, with levels maintained for 24 hours after administration, suggesting a strong immune response.

In clinical trials involving 9 patients, poly ICLC showed some neurological improvement in 3 cases, with one patient experiencing remission on a CT scan, while the treatment was generally well-tolerated with only mild side effects like fever and modest hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of interferon inducer (poly ICLC) in the treatment of malignant brain tumor (author's transl)]. Nakamura, O., Shitara, N., Matsutani, M., et al.[2020]

The administration of poly(I,C)-LC, a nontoxic immunotherapy, effectively eradicated established pulmonary metastases in experimental models, requiring 3 to 5 injections per week for at least 4 weeks for optimal results.

When combined with chemotherapy, poly(I,C)-LC improved survival rates in patients with high tumor burdens, suggesting it could serve as a valuable adjuvant treatment for cancer metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapeutic potential in murine tumor models of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose. Talmadge, JE., Adams, J., Phillips, H., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3104130/

A North American brain tumor consortium phase II study of ... Based on this study, poly-ICLC does not improve 6moPFS in patients with recurrent anaplastic gliomas but may be worth further study in combination with agents ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4779120/

A phase II clinical trial of poly-ICLC with radiation for adult ... This phase II study was designed to determine the overall survival time of adults with supratentorial glioblastoma treated with the immune modulator.

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/nct02078648

Safety and Efficacy Study of SL-701, a Glioma-Associated ... This is a multicenter, open-label Phase 1/2 study evaluating the efficacy and safety of SL-701 as a treatment for recurrent GBM, divided into 2 stages.

4. jeccr.biomedcentral.com jeccr.biomedcentral.com/articles/10.1186/s13046-021-02017-2

A systematic review on poly(I:C) and poly-ICLC in glioblastoma Poly(I:C) has shown therapeutic relevance as an adjuvant therapy to several treatment modalities, including vaccination and immune checkpoint blockade.

5. sciencedirect.com sciencedirect.com/topics/medicine-and-dentistry/carboxymethylcellulose-polycytidylic-polyinosinic-acid-polylysine

Carboxymethylcellulose Polycytidylic Polyinosinic Acid ... If validated in humans, this could theoretically improve fertility outcomes in the subset of women with a short luteal phase at baseline. Adjuvant therapies ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8229304/

A systematic review on poly(I:C) and poly-ICLC in glioblastoma In this review, we focused on polyinosinic:polycytidylic acid or poly(I:C), and its derivative stabilized with carboxymethylcellulose and poly-L ...

7. nature.com nature.com/articles/s41467-024-48073-y

TLR agonists polarize interferon responses in conjunction ... We report herein that ATL-DC vaccination with adjuvant poly-ICLC or resiquimod is overall safe and well-tolerated in patients with malignant ...