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Peginterferon alfa-2b in Treating Younger Patients with Recurrent or Refractory and Radiographically or Clinically Progressive Pilocytic Astrocytomas and Optic Pathway Gliomas

Trial Status: Active

This phase II trial studies how well peginterferon alfa-2b works in treating younger patients with pilocytic astrocytomas or optic pathway gliomas that have come back or do not respond to treatment and are growing, spreading, or getting worse. Peginterferon alfa-2b may stop tumor growth by preventing cell division and formation of blood vessels in the tumor, and by activating the immune system to attack tumor cells.

Inclusion Criteria

  • Patients with neurofibromatosis are eligible
  • Histologic confirmation is not required for this if the patient has neurofibromatosis type 1 (NF-1) with magnetic resonance imaging (MRI) findings consistent with optic pathway glioma or juvenile pilocytic astrocytoma (JPA); any other tumors will need histological confirmation, either at the time of diagnosis or at the time of recurrence; the histological diagnosis includes World Health Organization (WHO) grade I JPA
  • Patients must have measurable residual disease, defined as tumor that is measurable in two or three perpendicular diameters on MRI; for a lesion to be considered measurable, it must be at least twice the slice thickness on MRI (i.e visible on more than one slice)
  • All patients must have a brain MRI with and without contrast (gadolinium) within 30 days prior to study enrollment; all patients with history of spinal or leptomeningeal disease and those patients with symptoms suspicious of spinal disease, must have a spine MRI with contrast (gadolinium) performed within 30 days prior to study enrollment; lumbar puncture is necessary if there is evidence of tumor dissemination on the MRI of spine
  • Performance level: Karnofsky > or equal to 50% for patients > 10 years of age or Lansky > or equal to 50 for patients < 10 years of age; Note: patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • No limit in the number of previous surgical resections
  • No limit to number prior anti-cancer regimens, including chemotherapy, biologic agents, immunotherapy, vaccines, monoclonal antibodies or radiation therapy; patients who have received prior radiation therapy for this tumor are eligible; there should be at least 2 years time since the completion of radiation therapy
  • Patients must have recovered (to Common Toxicity Criteria [CTC] version [v.]5.0 =< grade 1 unless indicated below) from the acute toxic effects of all prior chemotherapy, immunotherapy prior to entering this study, with the exception of alopecia, weight changes and grade I or II lymphopenia
  • Myelosuppressive chemotherapy: must not have received within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
  • Biologic (anti-neoplastic agent): at least 7 days must have elapsed since the completion of therapy with other biologic agents; for other biologic agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
  • Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose of a monoclonal antibody; specifically for bevacizumab 36 days after the last dose
  • Resection: at least 3 weeks from the last surgical resection, prior to start study drug
  • Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
  • Radiation therapy (RT): patients must have had their last fraction of cranial or craniospinal radiation >= 24 months prior to study entry
  • Study specific limitations on prior therapy: * Patients who have received poly-ICLC are eligible for this trial if all acute poly-ICLC -related toxicity has resolved * Patients must not have received pegylated interferon previously
  • Growth factor(s): must not have received within 2 weeks of entry onto this study
  • Steroids: patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior enrollment in the study
  • Total bilirubin < 2.0 x the upper limit of normal and direct bilirubin within normal limits
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x the upper limit of normal
  • Patients with Gilbert syndrome are excluded from the requirement of a normal bilirubin but they must have an indirect bilirubin of < 6 mg/dl, and a direct bilirubin of < 0.5 mg/dl in order to be eligible; (Gilbert syndrome is found in 3-10% of the general population and is characterized by mild, chronic hyperbilirubinemia in the absence of liver disease or overt hemolysis)
  • Peripheral absolute granulocyte count of > 1000/mm^3
  • Hemoglobin > 8 gm/dL, patients may be transfused with red blood cells (RBC’s)
  • Platelet count > 100,000/mm^3; independent of transfusion
  • Patients must have an age-adjusted normal serum creatinine (see below) OR a creatinine clearance or glomerular filtration rate (GFR) >= or more than 60 mL/min/1.73 m^2 * Age (years); maximum serum creatinine (mg/dl) * < 5 years; 0.8 mg/dl * 5 < age < 10 years; 1.0 mg/dl * 10 < age < 15 years; 1.2 mg/dl * > 15 years; 1.5 mg/dl
  • No evidence of dyspnea at rest and pulse oximetry > 94%
  • If history of depression or psychiatric illness, has to be well controlled with antidepressants and/or under psychiatrist/ psychologist care

Exclusion Criteria

  • Patients who are receiving concurrent chemotherapy, or who are currently receiving other investigational chemotherapeutic agents or concurrently receiving radiation
  • Patients with a known hypersensitivity to interferon-alpha
  • Prior use of pegylated interferon or interferon
  • Less than 2 years since completion of radiation therapy
  • Pregnant or breast-feeding females are excluded
  • Patients with clinically significant unrelated systemic illness (including autoimmune disease, serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the principal or associate investigators would compromise the patient’s ability to tolerate this therapy or are likely to interfere with the study procedures or results
  • Dental braces or prosthesis that interferes with MR imaging
  • History of noncompliance to medical regimens
  • Patients unwilling to or unable to comply with the protocol
  • Patients with a positive history of hepatitis B or hepatitis C
  • Male patient whose sexual partner(s) are women of childbearing potential who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
  • Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period; close contact with those who have received attenuated live vaccines should be avoided during treatment with pegylated interferon; examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, bacillus Calmette-Guérin (BCG), yellow fever, varicella and TY21a typhoid vaccines
  • Patient with diagnosis of diffuse intrinsic pontine glioma

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: ACTIVE
Contact: Dolly Graciela Aguilera
Phone: 404-785-3515

PRIMARY OBJECTIVES:

I. To determine the objective response of children with recurrent or refractory and radiographically or clinically progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with pegylated interferon alpha-2b (peginterferon alfa-2b).

SECONDARY OBJECTIVES:

I. To estimate event free survival (EFS) (based on standard two or three-dimensional tumor measurements) for children with recurrent, refractory or progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with peginterferon (peginterferon alfa-2b).

II. To define the toxicities of long term weekly pegylated interferon alpha-2b in pediatric patients with refractory, recurrent and progressive juvenile pilocytic astrocytomas and optic pathway gliomas.

III. To compare response categories and EFS across the 3 magnetic resonance (MR) sequences (T2-weighted, fluid attenuation inversion recovery [FLAIR], T1-weighted post-contrast).

IV. To evaluate the quality of life for patients with recurrent, refractory and progressive juvenile pilocytic astrocytomas and optic pathway gliomas who receive therapy with pegylated interferon alpha-2b.

OUTLINE:

Patients receive peginterferon alfa-2b subcutaneously (SC) once weekly. Treatment repeats every 28 days for 26 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Children's Healthcare of Atlanta - Egleston

Principal Investigator
Dolly Graciela Aguilera

  • Primary ID CHOA2725-14
  • Secondary IDs NCI-2015-00181, IRB00074563
  • Clinicaltrials.gov ID NCT02343224