A Trial of Poly-ICLC in the Management of Recurrent Pediatric Low Grade Gliomas

• Status: Completed
• Trial end date: 2019-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is for patients up to 21 years of age who have a tumor called a low grade glioma of the central nervous system (brain and spinal cord). The tumor has grown despite attempts to control it with chemotherapy or radiation. Low grade gliomas are a group of tumors that tend to grow slowly and could be cured if every bit of the tumor were surgically removed. These tumors are called Grade I or II astrocytomas.

These tumors often grow in parts of the brain that prevent total removal without devastating neurologic complications or death. Although some low grade gliomas never grow, most will and are treated with either chemotherapy or radiation. There is good data showing that the growth of most low grade gliomas can be controlled with chemotherapy or radiation. However, some low grade gliomas in children and young adults grow despite these treatments. Poly-ICLC is a new drug that has been used safely in children and adults with different types of brain tumors. Earlier studies showed that this drug worked better for children and young adults with low grade gliomas than for children with more aggressive brain tumors. The main purpose of this study is to use Poly-ICLC treatment in a larger number of patients to see how well it works and how many side effects occur.

As Poly-ICLC is not FDA approved, this study is authorized to use it under IND# 43984, held by Oncovir.

Subjects will get injections of Poly-ICLC into muscle two times weekly. The first treatments will be given in the clinic so allergic or other severe reactions, if any, can be monitored. If subjects tolerate the injections and don't have a severe reaction, then the rest of the injections will be given at home. Subjects/caregivers will be trained to give injections.

Treatment will last for about 2 years. Subjects may stay on treatment for longer than 2 years if their tumor shrinks in response to the injections, if study doctors think it is safe, if subjects want to remain on treatment, and if Poly-ICLC is available.

Risks: Poly-ICLC has been used safely in children and adults at the dose used in this study, and at higher doses. Frequently seen side effects include irritation of the skin at the injection site and mild flu-like symptoms. These are usually relieved or avoided by use of over-the-counter medicines like acetaminophen (Tylenol).

Funding Source: FDA OOPD

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Donald Durden; Donald Durden, M.D.
• Collaborator: Emory University
• Treatments: Carboxymethylcellulose Sodium; Poly I-C; Poly ICLC

Criteria

Inclusion Criteria:

• Age:Patients must be between 0 - 21 years of age when registered on this protocol.

• Diagnosis:Patients must have pathologically confirmed low grade glioma with histologic subtypes interpreted as WHO grade I and II including:

• juvenile pilocytic astrocytoma (JPA)

• pleomorphic JPA

• diffuse astrocytoma (fibrillary, gemistocytic, giant cell, or pleomorphic xanthoastrocytoma)

• low grade oligoastrocytoma

• low grade oligodendroglioma

• low grade glioma NOS Tumors of all regions of the CNS, with appropriate histology are eligible for study. However patients with tumors intrinsic to the optic nerve and involvement of the optic nerve cannot be biopsied/resected are eligible without histological confirmation.

Patients with neurofibromatosis type 1(NF1) are also eligible.

Patients must have demonstrated either tumor progression or recurrence by radiographic criteria and/or clinical criteria as defined below:

1. Patients with progressive non-resectable disease regardless of location in the brain or spine are eligible for this study. Patients with evidence of leptomeningeal dissemination are eligible for this study. Patients do not require biopsy/histologic confirmation at the time of progression or relapse.

2. Radiographic progression is defined as >40% increase in the product of the three perpendicular diameters of initial tumor relative to the initial baseline measurement

• length (L)x width (W) x transverse (T) (current scan) > 1.4 x L x W x T (initial scan), or the development of any new sites of disease independent of the response of the initial tumor. See section 7.1.2 for methodology for tumor measurement.

3. Post radiation changes are often seen on post-treatment imaging studies, so that classification of a patient as having progressive disease may require several serial MRI's if the child has received radiation within the preceding 12 months.

4. Tumor volume includes the entire tumor volume seen on gadolinium enhanced T1 MR imaging plus non-enhancing abnormality seen on T2 or FLAIR.

5. All tumor cysts will be included in the tumor volume

6. Clinical progression without radiographic progression includes children with optic pathway gliomas who demonstrate sustained decrease in visual fields and/or acuity in three serial vision examinations. Each of the vision examinations must be performed >2 weeks apart.

7. Children with previously negative cerebrospinal fluid (CSF) cytology who show evidence of tumor cells in fluid obtained by lumbar puncture can be designated as having progressive disease in the absence of radiographic evidence of progression.

Measurable disease: Patients must have measurable disease documented by radiographic criteria prior to enrollment.

Performance Level and Life Expectancy:Patients must have a performance status of > 50% (Appendix I). Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age. Patients must have a life expectancy of ≥ 8 weeks.

Prior Therapy:Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and meet time restrictions from end of prior therapy as stated below:

1. Myelosuppressive chemotherapy patients must have received the last dose of myelosuppressive therapy at least 3 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 or biological agent >7 days prior to study registration

3. XRT: Patients must be ≥ 8 weeks since the completion of radiation therapy.

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

5. Growth factor(s): Must not have received any hematopoetic growth factors within 7 days of study entry or 21 days for neulasta.

6. Prior Surgery: Must be ≥ 2 weeks from prior surgery.

7. Steroids: Must be on a stable steroid dose for 7 days prior to study entry.

Organ Function Requirements:All patients must have adequate organ function defined as:

Hematologic Function:

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

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

3. Platelet Count: > 50,000 (transfusion independent; ≥ 7 days from last transfusion)

Renal Function:

Serum creatinine ≤ 2 x normal for age (see below) or Creatinine clearance/GFR > 60 cc/min/1.73 m2 [Urine Creatinine (mg/dL)][Volume collected (ml)]/[Serum Creatinine 9mg/dL)][Hours x 60]

Age (years) Maximum Serum Creatinine (mg/dL)

≤ 5 0.8 > 5 & ≤ 10 1.0 > 10 & ≤ 15 1.2 > 15 1.5

Liver Function:

1. Total bilirubin < 1.5 x ULN for age, AND

2. SGPT (ALT) < 2.5x ULN

3. SGOT (AST) < 2.5x ULN

Pulmonary Function:

No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry ≥ 94% if there is clinical indication for determination.

Coagulation Function:

Normal PT and PTT at enrollment per institutional range

Reproductive Function:Due to potential teratogenic effects of (poly-ICLC), negative serum beta-HCG in females, and use of effective contraception in males and females of childbearing potential, IS REQUIRED.

Exclusion Criteria:

• Pregnant or lactating females. Women of childbearing age will agree to use contraception during the protocol.

• Patients receiving other experimental immunotherapy.

• Patients may not have fever (38.50C) within 7 days of enrollment.

• No concurrent XRT or chemotherapy is allowed.

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