Clinical Trials /

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

NCT04544007

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. There will also be secondary and exploratory objectives listed in the detailed description below.

Related Conditions:
  • Low Grade Glioma
  • Neurofibromatosis Type 1
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: W81XWH-17-2-0037
  • NCT ID: NCT04544007

Conditions

  • NF1
  • Low-grade Glioma

Interventions

DrugSynonymsArms
Poly ICLCAdminister Poly-ICLC

Purpose

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.

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.
    

Trial Arms

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

Eligibility Criteria

        Inclusion Criteria:

          1. Age: Patients must be less than 22 years at the time of enrollment; there is no lower
             age limit.

          2. All participants must have an identified pathogenetic constitutional NF1 mutation OR
             the clinical diagnosis of NF1 using the NIH Consensus Conference criteria.

          3. 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.

          4. Patients must meet at least one of the following criteria for progression or
             recurrence of a previously treated target tumor:

               1. Progression or recurrence on MRI.

               2. New or worsening neurologic symptoms attributable to the target tumor.

               3. 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.

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

          6. Prior Therapy: Patients must have had at least one prior medical treatment for the
             target LGG.

          7. 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.

          8. 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:

               1. 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.

               2. 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.

               3. Radiation therapy: Patients SHOULD NOT have received prior irradiation.

               4. Study specific limitations on prior therapy: There is no limit on the number of
                  prior treatment regimens.

               5. 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.

               6. 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.

          9. Organ Function Requirements:

             All patients must have adequate organ function defined as:

             9.1 Hematologic Function:

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

               2. ANC: > 750/mm3. Must be at least 7 days after last dose of growth factor or > 14
                  days since last dose of pegylated GCSF

               3. 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:

               1. 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.)

               2. SGPT (ALT) ≤ 5 x ULN

               3. 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.

         10. Patient is able to start treatment within 7 days after enrollment.

         11. Patients with neurological deficits must be stable for a minimum of 1 week prior to
             enrollment.

         12. 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.

         13. Parents/legal guardians must provide written informed consent and agree that they will
             comply with the study.

        Exclusion Criteria:

          1. Prior radiation treatment for the low-grade glioma.

          2. Prior exposure to poly-ICLC.

          3. Patients currently receiving other anti-tumor therapy or experimental therapy
             (targeted agents, chemotherapy radiation).

          4. Patients with a current or prior diagnosis of malignant glioma (WHO grade III or IV).

          5. Patients with a prior diagnosis of malignant peripheral nerve sheath tumor or other
             malignancy requiring treatment in the last 48 months.

          6. Patients may not have fever (≥38.50 C) within 3 days of enrollment.

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

          8. Active auto-immune illness.

          9. Pregnant or lactating females.

         10. 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.

         11. Severe unresolved infection that requires systemic IV antibiotics.

         12. 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.

         13. 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.

         14. 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.
      
Maximum Eligible Age:22 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Evaluate the efficacy of poly-ICLC
Time Frame:First 48 weeks
Safety Issue:
Description: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)

Secondary Outcome Measures

Measure:Determine progression free survival (PFS)
Time Frame:12 Months
Safety Issue:
Description:a) Determine progression free survival (PFS) in pediatric NF1 patients with progressive LGG treated with poly-ICLC.
Measure:Determine progression free survival (PFS)
Time Frame:24 Months
Safety Issue:
Description:a) Determine progression free survival (PFS) in pediatric NF1 patients with progressive LGG treated with poly-ICLC.
Measure:Determine progression free survival (PFS)
Time Frame:60 Months
Safety Issue:
Description:a) Determine progression free survival (PFS) in pediatric NF1 patients with progressive LGG treated with poly-ICLC.
Measure:Evaluate efficacy by best objective tumor response rate (CR+PR)
Time Frame:24 Months
Safety Issue:
Description:b) Evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive LGG as measured by best objective tumor response rate (CR+PR).
Measure:Evaluate efficacy by clinical benefit response rate (CR+PR+MR+SD)
Time Frame:12 Months
Safety Issue:
Description:c) Evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive LGG as measured by clinical benefit response rate (CR+PR+MR+SD).
Measure:Evaluate efficacy by clinical benefit response rate (CR+PR+MR+SD)
Time Frame:24 Months
Safety Issue:
Description:c) Evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive LGG as measured by clinical benefit response rate (CR+PR+MR+SD).
Measure:Assess toxicity
Time Frame:Up to 60 months
Safety Issue:
Description:d) Assess the toxicity associated with poly-ICLC treatment in pediatric NF1 patients with LGG.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Alabama at Birmingham

Last Updated

September 2, 2020