Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors Non-Hodgkin Lymphoma or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)

  • STATUS
    Recruiting
  • End date
    Sep 30, 2024
  • participants needed
    49
  • sponsor
    National Cancer Institute (NCI)
Updated on 28 July 2021
platelet count
cancer
corticosteroids
ascites
stem cell transplantation
graft versus host disease
total body irradiation
lymphoma
hodgkin's disease
absolute neutrophil count
metastatic disease
nitrosoureas
tumor markers
cytokines
measurable disease
interferon
growth factor
pleural effusion
stem cell infusion
cns involvement
MRI
bone marrow procedure
glomerular filtration rate
international normalized ratio
hematopoietic growth factors
cytotoxic chemotherapy
metastasis
neutrophil count
tumor cells
blood transfusion
aptt
thromboplastin
cancer treatment
solid tumors
nitrosourea
graft-versus-host disease
chemotherapeutic agents
veliparib
interleukins
cancer therapy
antineoplastic
solid tumour
solid tumor
stem cell transplant
olaparib
blood count
cns metastases
match treatment
radiopharmaceutical therapy
antibody therapy
cns tumors
platelet transfusion
radiopharmaceutical
iobenguane
autologous stem cell infusion
pegfilgrastim
myelosuppressive chemotherapy
donor lymphocyte infusion
cellular therapy
platelet transfusions
anti-cancer agents
packed red blood cells
cns tumor
cns neoplasm
talazoparib
niraparib
pleural effusions
activated partial thromboplastin time (aptt)
central nervous system tumor
bone marrow infiltration
poly adenosine diphosphate ribose

Summary

This phase II Pediatric MATCH trial studies how well olaparib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with defects in deoxyribonucleic acid (DNA) damage repair genes that have spread to other places in the body (advanced) and have come back (relapsed) or do not respond to treatment (refractory). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Description

PRIMARY OBJECTIVES:

I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with olaparib with advanced solid tumors (including central nervous system [CNS] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in the deleterious genetic alterations in the DNA damage repair (DDR) pathway.

SECONDARY OBJECTIVES:

I. To estimate the progression free survival in pediatric patients treated with olaparib with advanced solid tumors including non-Hodgkin lymphomas, CNS tumors, and histiocytosis that harbor deleterious genetic alterations in the DDR pathway.

II. To obtain information about the tolerability of olaparib in children and adolescents with relapsed or refractory cancer.

III. To provide preliminary estimates of the pharmacokinetics of olaparib in children and adolescents with relapsed or refractory cancer.

EXPLORATORY OBJECTIVES:

I. To explore approaches to profiling changes in tumor genomics over time through the evaluation of circulating tumor DNA.

OUTLINE

Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

Details
Condition Malignant neoplasm of kidney, Rhabdoid Tumor, Glioma, Hereditary Neoplastic Syndrome, Histiocytosis, Nephroblastoma, Advanced Solid Tumor, Refractory Non Hodgkin Lymphoma, High Grade Glioma, Advanced Malignant Solid Neoplasm, Deleterious BRCA1 Gene Mutation, Recurrent Glioma, Recurrent Malignant Solid Neoplasm, Low Grade Glioma, Recurrent Childhood Malignant Germ Cell Tumor, Recurrent Osteosarcoma, Recurrent Neuroblastoma, Refractory Malignant Solid Neoplasm, Recurrent Childhood Ependymoma, Deleterious BRCA2 Gene Mutation, Recurrent Childhood Central Nervous System Neoplasm, Refractory Central Nervous System Neoplasm, Recurrent Childhood Soft Tissue Sarcoma, Recurrent Hepatoblastoma, Recurrent Medulloblastoma, Refractory Neuroblastoma, Recurrent Langerhans Cell Histiocytosis, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Glioma, Refractory Medulloblastoma, Refractory Osteosarcoma, Refractory Soft Tissue Sarcoma, Recurrent Childhood Rhabdomyosarcoma, Refractory Childhood Malignant Germ Cell Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Deleterious ATM Gene Mutation, Deleterious RAD51C Gene Mutation, Deleterious RAD51D Gene Mutation, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ependymoma, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Glioma, Refractory Hepatoblastoma, Refractory Rhabdomyosarcoma, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Advanced Malignant Solid Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Kidney Cancer, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Wilms' Tumor, Gliomas, Hereditary Cancer Syndromes, Renal Cancer, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Primary Central Nervous System Neoplasm, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, malignant glioma, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, Recurrent Childhood Non-Hodgkin Lymphoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Treatment laboratory biomarker analysis, pharmacological study, olaparib
Clinical Study IdentifierNCT03233204
SponsorNational Cancer Institute (NCI)
Last Modified on28 July 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621H based on the presence of an actionable mutation
Patients must have a body surface area >= 0.65 m^2 at enrollment
Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice
Note: The following do not qualify as measurable disease
Malignant fluid collections (e.g., ascites, pleural effusions)
Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
Previously radiated lesions that have not demonstrated clear progression post radiation
Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age
Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; 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
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors 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 and the study-assigned research coordinator
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
Stem cell infusions (with or without total body irradiation [TBI])
Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
Autologous stem cell infusion including boost infusion: >= 42 days
Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131iodine [I]-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
Patients must not have received prior exposure to olaparib, veliparib, niraparib, rucaparib, talazoparib or other poly adenosine diphosphate ribose polymerase inhibitors (PARPi)
For patients with solid tumors without known bone marrow involvement: peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment)
For patients with solid tumors without known bone marrow involvement: platelet count >= 100,000/mm^3 (within 7 days prior to enrollment) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive platelet or packed red blood cells [pRBC] transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment) or
A serum creatinine based on age/gender as follows (within 7 days prior to enrollment)
Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for female
Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for female
Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for female
Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL for female
Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL for female
Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for female
Patients with solid tumors: bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
Patients with solid tumors: serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment); (for the purpose of this study, the ULN for SGPT is 45 U/L)
Patients with solid tumors: serum albumin >= 2 g/dL (within 7 days prior to enrollment)
Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (within 7 days prior to enrollment)
International normalized ratio (INR) =< 1.5 (within 7 days prior to enrollment)
Patients must be able to swallow intact tablets
All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria

Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in girls who are post-menarchal; women of child-bearing potential and their partners should agree to use two (2) highly effective forms of contraception throughout study participation and for at least one (1) month after the last dose of olaparib; male study participants should avoid fathering a child or donating sperm during the study and for three (3) months after the last dose of olaparib
Concomitant medications
Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Investigational drugs: patients who are currently receiving another investigational drug are not eligible
Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible
Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
CYP3A/CYP3A4 agents: patients who are currently receiving drugs that are strong and moderate inducers or inhibitors of CYP3A or CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 21 days prior to enrollment to the end of the study
Patients who have an uncontrolled infection are not eligible
Patient who are known to be serologically positive for human immunodeficiency virus (HIV)
Patients with known active hepatitis (i.e. hepatitis B or C)
Patients who have received a prior solid organ transplantation are not eligible
Patients with symptomatic uncontrolled brain metastases; a scan to confirm the absence of brain metastases is not required; the patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to enrollment; patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
Patients with known symptomatic Fanconi anemia (FA), ataxia-telangiectasia (A-T) syndrome, Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are not eligible (asymptomatic carriers are acceptable)
Major surgery must not have occurred within 2 weeks prior to enrollment and patients must have recovered from any effects of any major surgery
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
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