Poly-ICLC for Low-Grade Glioma

(NF111 Trial)

Recruiting at19 trial locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: University of Alabama at Birmingham

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Radiation treatment, Malignant glioma, others

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called Poly-ICLC that boosts the immune system in children with NF1 who have brain tumors that don't respond to usual treatments. The goal is to see if this medication can help shrink or control the tumors by enhancing the body's natural defenses.

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.

What data supports the effectiveness of the treatment Poly ICLC for low-grade glioma?

Research shows that Poly ICLC, when used with other treatments, can boost the immune system's response against brain tumors like glioblastoma, which is a more aggressive type of brain cancer. This suggests it might help in treating low-grade glioma by enhancing the body's ability to fight the tumor. ^{1 2 3 4 5}

Is Poly-ICLC safe for humans?

Poly-ICLC has been shown to be generally safe in humans, with the most common side effect being fever. Other side effects like low blood pressure and low white blood cell count were mild and improved in a few days. ^{1 2 6 7 8}

How is the drug Poly-ICLC unique for treating low-grade glioma?

Poly-ICLC is unique because it acts as an immune modulator, potentially enhancing the body's immune response to fight glioma by priming or boosting immune cells, unlike traditional treatments that primarily focus on directly targeting the tumor. ^{1 2 5 7 9}

Research Team

Juliette Southworth, BS, CCRP

Principal Investigator

University of Alabama at Birmingham, NFCTC

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Poly ICLC (Virus Therapy)

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.

Participant Groups

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).

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Kierstin Kennedy

University of Alabama at Birmingham

Chief Medical Officer since 2022

MD

S. Dawn Bulgarella

University of Alabama at Birmingham

Chief Executive Officer since 2023

BSc in Commerce and Business Administration from the University of Alabama, MS in Health Administration from the University of Alabama at Birmingham

Children's Healthcare of Atlanta

Collaborator

Trials

172

Recruited

108,000+

Donna Hyland

Children's Healthcare of Atlanta

Chief Executive Officer since 2008

Bachelor of Science in Management from Georgia Tech, MBA from Northwestern University’s Kellogg School of Management

Dr. Srikant Iyer

Children's Healthcare of Atlanta

Chief Medical and Quality Officer

MD from the University of North Carolina at Chapel Hill, Master of Public Health from Harvard University

Children's Hospital Los Angeles

Collaborator

Trials

257

Recruited

5,075,000+

Paul S. Viviano

Children's Hospital Los Angeles

Chief Executive Officer since 2015

Master of Public Health from UCLA Fielding School of Public Health

Alan S. Wayne

Children's Hospital Los Angeles

Chief Medical Officer since 2023

MD

Findings from Research

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]

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]

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]

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]

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 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 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]

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]

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]

References

1. United States 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). [2022]

2. England pubmed.ncbi.nlm.nih.gov

A systematic review on poly(I:C) and poly-ICLC in glioblastoma: adjuvants coordinating the unlocking of immunotherapy. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Immunotherapeutic potential in murine tumor models of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose. [2021]

4. United States 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. [2020]

5. United States 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. [2020]

6. Japan pubmed.ncbi.nlm.nih.gov

[Effect of interferon inducer (poly ICLC) in the treatment of malignant brain tumor (author's transl)]. [2020]

7. England 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. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Phase I-II trials of poly(ICLC) in malignant brain tumor patients. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Sustained Delivery of Doxorubicin via Acetalated Dextran Scaffold Prevents Glioblastoma Recurrence after Surgical Resection. [2019]