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

NCT04544007 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: W81XWH-17-2-0037
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 12

Brief 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 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.

Conditions

NF1; Low-grade Glioma

Outcome Measures

Primary Outcomes (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assessment, or through the last tumor assessment time during this nominal period for patients in follow-up but who have withdrawn from protocol therapy, or through the last available tumor assessment for patients who are lost to follow-up during this time.

  First 48 weeks

Secondary Outcomes (6)

• Determine Progression Free Survival (PFS)

  12 months

• Determine Progression Free Survival (PFS)

  24 Months

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

  24 Months

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

  12 Months

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

  24 Months

Study Arms (1)

Administer Poly-ICLC

EXPERIMENTAL

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

Drug: Poly ICLC

Interventions

Poly ICLC DRUG

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

Also known as: Hiltonol

Administer Poly-ICLC

Eligibility Criteria

• Age: Up to 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Children's Healthcare of Atlanta: collaborator
• Children's Hospital Los Angeles: collaborator

Study Sites (12)

The University of Alabama at Birmingham (Site 700)

Birmingham, Alabama, 35294, United States

Location

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Children's National Medical Center (Site 775)

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30342, United States

Location

Children's Lurie Hospital

Chicago, Illinois, 60611, United States

Location

Lurie Children's Hospital of Chicago (Site 350)

Chicago, Illinois, 60611, United States

Location

University of Chicago (Site 850)

Chicago, Illinois, 60637, United States

Location

Washington University - St. Louis (Site 900)

St Louis, Missouri, 63110, United States

Location

New York University Medical Center (Site 200)

New York, New York, 10016, United States

Location

Cincinnati Children's Hospital Medical Center (Site 800)

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia (Site 750)

Philadelphia, Pennsylvania, 19096, United States

Location

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

Dallas, Texas, 75235, United States

Location

MeSH Terms

Interventions

poly ICLC

Results Point of Contact

• Title: Coretta Thomas, Scientist & Data Manager for NF Consortium
• Organization: University of Alabama at Birmingham

coretta@uab.edu

205-975-8629

Study Officials

• Juliette Southworth, BS, CCRP

  University of Alabama at Birmingham, NFCTC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Dean for Genomic Medicine, UAB School of Medicine and Chief Genomics Officer, UAB Medicine

Model Details: 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)

Study Record Dates

• First Submitted: September 2, 2020
• First Posted: September 10, 2020
• Study Start: February 8, 2022
• Primary Completion: January 4, 2024
• Study Completion: November 15, 2024
• Last Updated: March 21, 2025
• Results First Posted: March 21, 2025

Record last verified: 2025-03

Locations

US (12)