PBTC45: MK-3475 in Treating Children with Recurrent, Progressive or Refractory HGGs and DIPGs

A Safety and Preliminary Efficacy Trial of MK-3475 (Pembrolizumab; anti PD-1) in Children with Recurrent, Progressive or Refractory High-Grade Gliomas (HGG) and DIPGs

Categories:

Brain Tumor

Solid Tumor

Diseases Treated:

Recurrent, progressive, or refractory high-grade gliomas

Eligibility Overview:

  • Participant has recurrent, progressive or refractory non-brainstem high-grade glioma or diffuse intrinsic pontine glioma (DIPG)
  • Participant is 1 to 18 years of age.
  • Participant has received prior radiation therapy and/or chemotherapy and has not received myelosuppressive anticancer chemotherapy for at least three (3) weeks

Description

This clinical trial studies the side effects and best dose of MK-3475 (pembrolizumab) and to see how well it works in treating younger patients with high-grade gliomas (brain tumors) or diffuse intrinsic pontine gliomas (brain stem tumors) that have come back, progressed, or have not responded to previous treatment. The immune system can attack tumors and suppress their growth, however many tumors are able to slow down or stop this immune response. Monoclonal antibodies such as MK-3475 may help the immune system better target the tumor. MK-3475 will be given intravenously every three weeks. MK-3475 is experimental and has been tested in adults but not in children.

Primary Objectives

  • To establish the safety and describe adverse effects associated with administration of the adult recommended dose of MK-3475 (pembrolizumab) in children with recurrent, progressive or refractory non-brainstem high grade glioma (NB-HGG) and diffuse intrinsic pontine glioma (DIPG).
  • To estimate the sustained objective response rate, (CR+PR, sustained for at least 9 weeks) associated with MK-3475 (pembrolizumab) treatment for pediatric patients with recurrent, progressive or refractory NB-HGG or DIPG. This assessment will be done separately in two strata, NB-HGG and DIPG.

Eligibility Criteria

Inclusion criteria (among others):

  • Participant has a histologically confirmed diagnosis of recurrent, progressive or refractory non-brainstem high-grade glioma (NB-HGG) or participant has a diffuse intrinsic pontine glioma (DIPG) that is recurrent, progressive or refractory.
  • Participant enrolling during the safety portion of the study is greater than or equal to one (1) years and less than eighteen (18) years of age at the time of enrollment, or participants enrolling during the efficacy portion of the study are less than twenty-two (22) years of age.
  • Participant has received prior radiation therapy and/or chemotherapy and has recovered from the acute treatment related toxicities (defined as less than grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study. Note: There is no upper limit to the number of prior therapies that are allowed.
  • Participant has not received myelosuppressive anticancer chemotherapy for at least three (3) weeks (6 weeks for nitrosurea or mitomycin-C) prior to enrollment.
  • Participant has appropriate liver and kidney function as determined by protocol specific lab value criteria (see protocol for lab specific lab values).
  • Participant received last dose of investigational or biologic agent greater than or equal to seven (7) days prior to study enrollment.

Exclusion criteria (among others):

  • Participant with active autoimmune disease or documented history of autoimmune disease/syndrome that requires ongoing systemic steroids or systemic immunosuppressive agents except participants with vitiligo or resolved asthma/atopy or participants with hypothyroidism stable on hormone replacement or Sjogren’s syndrome.
  • Participant with history of or ongoing pneumonitis or significant interstitial lung disease.
  • Participant with other malignancies.
  • Participant known to have active Hepatitis B (HbsAg active) or Hepatitis C (HCV RNA-qualitative is detected).
  • Participant has a history of severe hypersensitivity reaction to a monoclonal antibody.

For the current eligibility status of this clinical study, referring physicians must contact St. Jude Children's Research Hospital at 1-866-2ST-JUDE (1-866-278-5833).

Contact

Alberto Broniscer, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Phone: 901-595-2544 or 901-595-4599
Fax: 901-595-6211

OR

Tabatha E. Doyle, RN
Coordinator, Brain Tumor Program
MS 260
262 Danny Thomas Place
Memphis, TN 38105
Phone: (901) 595-2544
FAX: (901) 595-6211

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.