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NF1Phase 2NF111NCT04544007

A Phase II Trial of Poly-ICLC for Low-Grade Gliomas

A Phase 2 study testing Poly ICLC in people with NF1 and Low-grade Glioma, run by University of Alabama at Birmingham at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a phase II, prospective, longitudinal, multi-center trial of poly-ICLC (Hiltonol ®) treatment for progressive low-grade gliomas in pediatric patients with NF1. The primary objective is to evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive low-grade glioma (LGG) as measured by… Read more about this study

Who is it for?
Ages Up to 22 years
Conditions the study is for
NF1, Low-grade Glioma
What is being tested?
Poly ICLC
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
12 sitesUnited States
Study dates
8 Feb 2022to 15 Nov 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 22 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age: Patients must be less than 22 years at the time of enrollment; there is no lower age limit.
  • All participants must have an identified pathogenetic constitutional NF1 mutation OR the clinical diagnosis of NF1 using the NIH Consensus Conference criteria.
  • Diagnosis: LGG (WHO Grade 1 and 2) of the brain and spinal cord are eligible. Histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings. Biopsy for histologic diagnosis is required if there is clinical suspicion for a high-grade tumor; special attention is recommended in older adolescents or young adults to the potential for malignant transformation. Patients with metastatic disease are eligible.
  • Patients must meet at least one of the following criteria for progression or recurrence of a previously treated target tumor:
  • Progression or recurrence on MRI.
  • New or worsening neurologic symptoms attributable to the target tumor.
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  • For patients with OPG: visual worsening, defined as worsening of visual acuity (VA) or visual fields (VF) documented within the past year by examination or history, attributable to tumor.
  • Measurable Disease: Patients must have two-dimensional measurable tumor >1cm2.
  • Prior Therapy: Patients must have had at least one prior medical treatment for the target LGG.
  • Performance Level: Patients must have a performance status of equal or > than 50 using Karnofsky for patients equal or ≥ 16 years of age and Lansky for patients < 16 years of age.
  • Patients must have recovered to grade ≤1 from any acute toxicities from all prior treatments. to enroll on this study and meet time restrictions from end of prior therapy as defined below:
  • Myelosuppressive chemotherapy: must have received the last dose of myelosuppressive therapy at least 4 weeks prior to study registration, or at least 6 weeks if nitrosourea.
  • Investigational/biological agent: Patient must have received the last dose of other investigational, immunotherapy, or biological agent > 14 days prior to study registration or at least 5 half-lives, whichever is greater. Bevacizumab last dose > 36 days prior to enrollment.
  • Radiation therapy: Patients SHOULD NOT have received prior irradiation.
  • Study specific limitations on prior therapy: There is no limit on the number of prior treatment regimens.
  • Growth factor(s): Must not have received any hematopoietic growth factors within 7 days of study entry or > 14 days if pegylated GCSF is used.
  • Prior surgery: At the time of enrollment, must be ≥ 3 weeks from prior major surgery such as craniotomy, orthopedic surgery, abdominal surgery or ≥1 week from minor surgery and completely recovered. Port or central line placement is not considered a major surgery.
  • Organ Function Requirements:
  • All patients must have adequate organ function defined as:
  • 9.1 Hematologic Function:
  • Hemoglobin: > 8.0 gm/dl (may transfuse PRBCs)
  • ANC: > 750/mm3. Must be at least 7 days after last dose of growth factor or > 14 days since last dose of pegylated GCSF
  • Platelet Count: > 75,000/mm3 (transfusion independent; ≥ 7 days from last transfusion)
  • 9.2 Renal Function: Serum creatinine which is less than 1.5 times ULN for age (as per the table below) or GFR > 70 ml/min/1.73m2
  • Renal Function Normal for Age
  • Age Maximum Serum Creatinine (mg/dL) Male Female 1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4
  • ≥ 16 years 1.7 1.4
  • Liver Function:
  • Total bilirubin < 1.5 x ULN (Children with diagnosis of Gilbert's Syndrome will be allowed on the study regardless of their total and indirect bilirubin levels as long as the direct bilirubin is less than 3.1 mg/dL.)
  • SGPT (ALT) ≤ 5 x ULN
  • SGOT (AST) ≤ 5 x ULN
  • Pulmonary Function:
  • No evidence of dyspnea at rest, and a pulse oximetry ≥ 92%.
  • Reproductive Function:
  • Female patients of childbearing potential must have negative serum or urine pregnancy test within 7 days prior to the first dose of poly-ICLC. Patient must not be pregnant or breast-feeding. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, including abstinence, while being treated on this study and for 90 days following cessation of treatment.
  • Patient is able to start treatment within 7 days after enrollment.
  • Patients with neurological deficits must be stable for a minimum of 1 week prior to enrollment.
  • Patients are only eligible if complete resection of the LGG with acceptable morbidity is not feasible, or if a patient with a surgical option refuses surgery.
  • Parents/legal guardians must provide written informed consent and agree that they will comply with the study.

Who cannot join

  • Prior radiation treatment for the low-grade glioma.
  • Prior exposure to poly-ICLC.
  • Patients currently receiving other anti-tumor therapy or experimental therapy (targeted agents, chemotherapy radiation).
  • Patients with a current or prior diagnosis of malignant glioma (WHO grade III or IV).
  • Patients with a prior diagnosis of malignant peripheral nerve sheath tumor or other malignancy requiring treatment in the last 48 months.
  • Patients may not have fever (≥38.50 C) within 3 days of enrollment.
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  • Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
  • Active auto-immune illness.
  • Pregnant or lactating females.
  • 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.
  • Severe unresolved infection that requires systemic IV antibiotics.
  • Patients with any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, impaired gastrointestinal function, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients requiring high doses of steroids. Patients may not be on immunosuppressive therapy, including corticosteroids (with the exception of physiologic replacement, defined as ≤ 0.75 mg/m2/day dexamethasone or equivalent) at time of enrollment. However, patients who require intermittent use of bronchodilators or local steroid injections will not be excluded from the study.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30342

  • The University of Alabama at Birmingham (Site 700)

    Birmingham, Alabama, 35294

  • Children's Lurie Hospital

    Chicago, Illinois, 60611

  • Lurie Children's Hospital of Chicago (Site 350)

    Chicago, Illinois, 60611

  • University of Chicago (Site 850)

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center (Site 800)

    Cincinnati, Ohio, 45229-3039

  • Childrens Medical Center - Univ. of Texas SW (Site 917)

    Dallas, Texas, 75235

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90027

  • New York University Medical Center (Site 200)

    New York, New York, 10016

  • Children's Hospital of Philadelphia (Site 750)

    Philadelphia, Pennsylvania, 19096

  • Washington University - St. Louis (Site 900)

    St Louis, Missouri, 63110

  • Children's National Medical Center (Site 775)

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Phase II Trial of Poly-ICLC for Progressive, Previously Treated Low-Grade Gliomas in Children and Young Adults With Neurofibromatosis Type 1

This is a phase II, prospective, longitudinal, multi-center trial of poly-ICLC (Hiltonol ®) treatment for progressive low-grade gliomas in pediatric patients with NF1. The primary objective is to evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive low-grade glioma (LGG) as measured by objective tumor response rate (CR+PR) within the first 48 weeks (12 cycles) of therapy. There will also be secondary and exploratory objectives listed in the detailed description below.

Read the detailed description

This is a phase II, prospective, longitudinal, multi-center trial of poly-ICLC (Hiltonol ®) treatment for progressive low-grade gliomas in pediatric patients with NF1. The primary objective is to evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive low-grade glioma (LGG) as measured by objective tumor response rate (CR+PR) within the first 48 weeks (12 cycles) of therapy.

The secondary objectives are to:

  1. Determine 12, 24 and 60 month progression free survival (PFS) in pediatric NF1 patients with progressive LGG treated with poly-ICLC.
  2. Evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive LGG as measured by best objective tumor response rate (CR+PR) within 24 cycles of therapy.
  3. Evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive LGG as measured by clinical benefit response rate (CR+PR+MR+SD) after 12 and 24 cycles of therapy.
  4. Assess the toxicity associated with poly-ICLC treatment in pediatric NF1 patients with LGG.

Exploratory objectives are to:

  1. Evaluate the visual outcome measures in children with progressive optic pathway gliomas treated with poly-ICLC. Visual response is defined as 0.2 logMAR or greater in acuity improvement.
  2. Evaluate patient reported outcomes and quality of life measures.
  3. Evaluate biological correlates.
Being tested
Poly ICLC

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Poly ICLCDrug

    Also called Hiltonol

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

Study groups in NCT04544007
Study groupRoleWhat they receive
Administer Poly-ICLCExperimentalEnrolled participants will receive poly-ICLC 20 mcg/kg/dose twice weekly IM (using Monday/Thursday or Tuesday/Friday schedule if possible).
Receives: Drug: Poly ICLC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluate the Efficacy of Poly-ICLC

    Evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive low-grade glioma (LGG) as measured by objective tumor response rate (CR+PR), using Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria. Complete Response (CR) is complete disappearance of the target lesion on T2 weighted and T2 weighted fluid attenuated inversion recovery (FLAIR) imaging and contrast imaging using baseline MRI or best recorded response for comparison; Partial Response (PR) is 50% or greater reduction in the target lesion on T2 weighted and T2 weighted-FLAIR imaging using the baseline MRI for comparison. Response will be assessed through the time of the post-12th cycle tumor assessment, or through the last tumor assessment time during this nominal period for patients in follow-up but who have withdrawn from protocol therapy, or through the last available tumor assessment for patients who are lost to follow-up during this time.

    Measured: First 48 weeks

Secondary outcomes (6)

  1. Determine Progression Free Survival (PFS)

    Determine progression free survival (PFS) in pediatric NF1 patients with progressive LGG treated with poly-ICLC. Progression free survival (PFS), defined as the time from start of treatment to the first occurrence of tumor recurrence, tumor progression, occurrence of a second malignancy, or death from any cause. Patients event-free at last follow-up will be censored in analysis. PFS will be determined at 12, 24 and 60 months.

    Measured: 12 months

  2. Determine Progression Free Survival (PFS)

    Determine progression free survival (PFS) in pediatric NF1 patients with progressive LGG treated with poly-ICLC. Progression free survival (PFS), defined as the time from start of treatment to the first occurrence of tumor recurrence, tumor progression, occurrence of a second malignancy, or death from any cause. Patients event-free at last follow-up will be censored in analysis. PFS will be determined at 12, 24 and 60 months.

    Measured: 24 Months

  3. Number of Participants Who Achieved Best Objective Tumor Response Rate (CR+PR)

    Evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive LGG as measured by best objective tumor response rate (CR+PR) within 24 cycles of therapy. Objective response rate (defined as CR or PR) after 24 cycles of treatment. Response will be assessed through the time of the post-24th cycle tumor assessment, or through the last tumor assessment time during this nominal period for patients in follow-up, but who have withdrawn from protocol therapy, or through the last available tumor assessment for patients who are lost to follow-up during this time.

    Measured: 24 Months

  4. Evaluate Efficacy by Clinical Benefit Response Rate (CR+PR+MR+SD)

    Evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive LGG as measured by clinical benefit response rate (CR+PR+MR+SD). Clinical benefit defined as (CR+PR+MR+SD). Clinical benefit will be assessed through the time of the post-12 and 24th cycle tumor assessment, or through the last tumor assessment time during this nominal period for patients in follow-up but who have withdrawn from protocol therapy, or through the last available tumor assessment for patients who are lost to follow-up during this time.

    Measured: 12 Months

  5. Evaluate Efficacy by Clinical Benefit Response Rate (CR+PR+MR+SD)

    Evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive LGG as measured by clinical benefit response rate (CR+PR+MR+SD). Clinical benefit defined as (CR+PR+MR+SD). Clinical benefit will be assessed through the time of the post-12 and 24th cycle tumor assessment, or through the last tumor assessment time during this nominal period for patients in follow-up but who have withdrawn from protocol therapy, or through the last available tumor assessment for patients who are lost to follow-up during this time.

    Measured: 24 Months

  6. Assess Toxicity

    Assess the toxicity associated with poly-ICLC treatment in pediatric NF1 patients with LGG. The grade and duration of CTCAE toxicities observed during treatment, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 for reporting of adverse events.

    Measured: Up to 24 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2020
  2. Study start8 Feb 2022
  3. Primary completion4 Jan 2024
  4. Study completion15 Nov 2024

Why it stopped: The closure of the study is due to the lack of enrollment and the lack of evaluable patients.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Patients must be less than 22 years of age with a diagnosis of NF1 and LGG of the brain and spinal cord (WHO Grade 1 and 2)
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04544007
Sponsor's protocol ID
W81XWH-17-2-0037
Acronym
NF111
Status last verified
Mar 2025
First submitted
2 Sep 2020
Last updated
21 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Poly ICLC in people with NF1 and Low-grade Glioma, run by University of Alabama at Birmingham at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 39 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate the Efficacy of Poly-ICLC (time frame: First 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04544007.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2025.

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