Symptoms and General Pathology

All Conditions

Catastrophic Illness

Disease Attributes

All participants enrolled on this study will have blood drawn for genetic testing.

Clinton F. Stewart, Pharm.D.

Jun J. Yang, Ph.D.

To investigate whether genetic polymorphisms in genes encoding proteins involved in the metabolism or effects of drugs or environmental agents influence the disposition or effects of these xenobiotic substrates. To investigate the nature of heritability and the genetic basis of pharmacogenetic traits by studying family members of individuals with specific genotypes.

Pharmacogenetics is that discipline devoted to elucidating the genetic determinants of drug response. Particularly in the area of drug metabolism, many genes exhibit genetic polymorphism; that is, a stable percentage of the population (which generally differs by ethnic group) is deficient in the functional expression of the enzyme involved, and the deficiency is typically inherited as an autosomal recessive trait. With currently known polymorphisms in drug metabolism, the percentage of homozygous deficient individuals ranges from 0.3% to as many as 90% of the population, depending on the enzyme and the ethnic group.

Our prior studies have revealed multigenic pharmacogenetic models that are significantly predictive of various drug response phenotypes (e.g., drug resistance, drug clearance, drug toxicity, disease response) in children with ALL. The large number of candidate loci and the relatively small number of patients illustrate the fact that larger sample sizes are required to definitively establish these polygenic models. The fact that there were significant race/genotype interactions, such that predictions differed in whites vs blacks, highlights the need for adequate numbers of patients within racial and ethnic groups to allow differential analysis of genotypic predictors after adjusting for confounding demographic factors in pharmacogenetic studies via stratified design and analyses.

DNA or RNA for genetic testing will typically be obtained simultaneously with blood that is drawn for clinical reasons.

Pharmacogenetic Determinants Of Treatment Response In Children

National Cancer Institute (NCI)

National Institute of General Medical Sciences (NIGMS)

St. Jude Children's Research Hospital

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Lymphoma, Large B-Cell, Diffuse

Sarcoma

Lymphoma

Hematologic Neoplasms

Lymphoma, Follicular

Mesothelioma

Mesothelioma, Malignant

Lymphoma, B-Cell

Carcinoma, Medullary

Sarcoma, Synovial

Rhabdoid Tumor

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Connective and Soft Tissue

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms, Mesothelial

Hematologic Diseases

Neoplasms, Connective Tissue

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Soft Tissue Sarcoma

Lymphosarcoma

Follicular Lymphoma

Malignant Mesothelioma

Thyroid Cancer, Medullary

Renal Medullary Carcinoma

Synovial Sarcoma

Epithelioid Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

Anti-Infective Agents

All Drugs and Chemicals

Itraconazole

Rifampin

Hydroxyitraconazole

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Participants in Part 1 of the study will receive a single oral, 400 mg dose of tazemetostat on Day 1, 15, and Day 36.

The study participants will receive tazemetostat (oral 400 mg) tablets to be taken twice daily on Days 3 - 14 and Days 21 - 35. In addition, the participants will receive oral 200 mg itraconazole once daily on Days 18 - 38.

Study participants may continue tazemetostat from Day 40+ at the recommended therapeutic dose (oral 800 mg twice daily) in 28-day cycles.

Participants in Part 2 of the study will receive a single oral, 800 mg dose of tazemetostat on Days 1, 15, and Day 36.

The study participants will receive tazemetostat (oral 800 mg dose) tablets to be taken twice daily on Days 3 - 14 and Days 17 - 23. In addition, the participants will receive oral 200 mg rifampin once daily on Days 17 - 25.

Study participants may continue tazemetostat from Day 27+ at the recommended therapeutic dose (oral 800 mg twice daily) in 28-day cycles.

A single, oral, 400 mg dose of tazemetostat on Day 1, Day 15, and Day 36; and tazemetostat (oral 400 mg) tablets twice daily on Days 3 - 14 and Days 21 - 35.

Tazemetostat

Oral 200 mg itraconazole once daily on Days 18 - 38

A single, oral, 800 mg dose of tazemetostat on Days 1, 15, and Day 24 ; and tazemetostat (oral 800 mg) twice daily on Days 3 - 14 and on Days 17 - 23.

Oral 600 mg rifampin once daily on Days 17 - 25.

Ipse Medical Director

The participants of this study will have advanced malignancies (also known as advanced cancer). The main aim of this trial will be to study the blood levels (known as pharmacokinetics) of the tazemtostat (the study drug) when administered in combination with another drug.

Part 1 of the study will evaluate the interaction between the drugs tazemetostat and itraconazole.

Part 2 of the study will evaluate the interaction between the drugs tazemetostat and rifampin

For both Parts 1 and 2, safety and the level that effects of the study drug can be tolerated (known as tolerability) will be assessed throughout.

This two-part study is designed to characterize the steady-state PK of oral tazemetostat and its metabolite EPZ 6930 when administered as a single and twice daily dose in subjects with advanced malignancies while taken alone or in combination with either itraconazole or rifampin.

Part 1: tazemetostat and Itraconazole Drug Interaction Part 1 of the study will evaluate the drug-drug interaction between tazemetostat and itraconazole in an open-label, fixed sequential cross over design.

Part 2: tazemetostat and Rifampin Drug Interaction Part 2 of the study will evaluate the drug-drug interaction between tazemetostat and rifampin in an open-label, fixed sequential cross over design.

For both Parts 1 and 2, safety and tolerability will be assessed throughout the subject's participation. Subjects must have an end of study visit after 30 days of the last dose of tazemetostat for safety assessment.

Study to Describe the Interaction Between Tazemetostat and Itraconazole and Between Tazemetostat and Rifampin in Participants With Advanced Cancer

A Phase I, Open-label Multi-dose Two-part Study to Characterize the Effects of a Strong CYP3A4 Inhibitor and a Strong CYP3A4 Inducer on the Steady-State Pharmacokinetics of Tazemetostat (EPZ-6438) in Subjects With Advanced Malignancies

Severity of adverse events experienced by all subjects with at least 1 dose or partial dose of tazemetostat will be evaluated by the Investigator based on the CTCAE, version 5.0.

Percentage of participants with clinically significant changes in physical examination findings will be reported. The clinical significance will be graded by the investigator.

Percentage of participants with clinically significant changes in Vital Signs will be reported. The clinical significance will be decided by the investigator.

Percentage of participants with clinically significant changes in ECG readings will be reported. The clinical significance will be graded by the investigator.

ECOG is a 4-point performance status scale used to assess performance as a key indicator (e.g., 0 = fully active, 2 = up and about more than 50% of walking hours, 4 = Completely disabled). Performance status will be assessed per usual clinical practice and will be recorded in the medical record.

All prior medications administered 30 days before study drug administration will be recorded.

Epizyme, Inc.

To compare the nutrition risk identification abilities of two nutrition screening tools: PEDSGA tool and the standard assessment tool.

Nutritional Screening Tools

Karen Smith, RD, MS, LDN

Researchers are studying ways to predict if cancer patients are at risk for poor nutrition during their chemotherapy treatment. They hope to identify children with nutrition problems early in treatment. This may help prevent weight loss and other nutrition problems later in treatment.

The PEDSGA is a newly developed nutrition tool that includes a training manual that be used to teach health care professionals to identify at-risk patients by doing a nutrition physical exam. The PEDSGA also includes questions that the patient/caregiver answers regarding appetite, recent treatment, and activity level. This method of screening is new and may be able to identify at-risk patients better than the standard method. This study will use both methods and evaluate the two, in hope of determining which method works best to identify at-risk patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pharmacogenetic Determinants Of Treatment Response In Children	NCT00730678	All Malignancie... Children Being ...		-	St. Jude Children's Research Hospital
Study to Describe the Interaction Between Tazemetostat and Itraconazole and Between Tazemetostat and Rifampin in Participants With Advanced Cancer	NCT04537715	All Malignancie... Advanced Malign... Hematologic Mal... Solid Tumor Follicular Lymp... Non-Hodgkin Lym... Diffuse Large B... Epithelioid Sar... Synovial Sarcom... Renal Medullary... Mesothelioma Rhabdoid Tumor	Tazemetostat Itraconazole Tazemetostat Rifampin	18 Years -	Ipsen
Pilot Test for a Newly Developed Nutrition Screening Method: Pediatric Subjective Global Assessment	NCT00665691	Compare Two Nut...	Nutritional Scr...	2 Years - 16 Years	St. Jude Children's Research Hospital

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