- Patients ≥ 12 years of age at the time of enrollment
- Performance status: 12-15 years old: Lansky > 50; 16-17 years old: Karnofsky > 50; ≥
18 years old: Eastern Cooperative Group (ECOG) score 0-2
- Subjects must have adequately recovered from the acute toxic effects of all prior
anti-cancer therapy per enrolling physician and must meet the following minimum
duration from prior anti-cancer directed therapy prior to enrollment.
- Anti-cancer agents not known to be myelosuppressive: > 7 days after the last dose
- 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.
- Systemic Corticosteroids: if related to prior therapy > 14 days must have
elapsed, or on stable dose for treatment of CNS disease.
- Hematopoietic growth factors: > 14 days after the last dose of a long-acting
- Interleukins, Interferons, and Cytokines (other than hematopoietic growth
factors): > 21 days after the completion of interleukins, interferon or cytokines
(other than hematopoietic growth factors).
- 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 BM radiation.
- Radiopharmaceutical therapy: > 42 days after systemically administered
- Major surgery > 14 days prior, with evidence of wound healing and no active
- Subjects must not have had prior exposure to Tazemetostat or other inhibitor(s) of
- Adequate laboratory values of organ function, defined as:
- Peripheral absolute neutrophil count (ANC) > 1000/mm3.
- Platelet count > 100,000/mm2 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment).
- Hemoglobin > 8.0 g/dL at baseline (may receive RBC transfusions).
- Creatinine clearance or radioisotope GFR > 70 ml/min/1.73 m2, or serum creatinine
based on age/gender
- Total bilirubin < 1.5 ULN or direct bilirubin < 1 x ULN.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN;
if liver metastases present, then AST and ALT must be < 5 x ULN.
- Serum albumin > 2 g/dL.
- Coagulation INR < 1.5, while on anti-coagulation INR < 2.5.
- Nervous system disorders (CTCAE v5.0) resulting from prior therapy must be < Grade 2,
with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible.
- Subjects must not have more than one active malignancy at the time of enrollment
- Presence of radiographically measurable disease per RECIST 1.1 criteria.
- Written informed consent obtained from the subject and the subject agrees to comply
with all the study-related procedures. All subjects and/or their parents or legally
authorized representatives must sign a written informed consent. Assent, when
appropriate, will be obtained according to institutional standard practice.
- Use of contraception:
- Women of childbearing potential (WOCBP) who are heterosexually active must be
using two highly effective methods of contraception to avoid pregnancy throughout
the study and for at least 30 days after the last dose of study drug to minimize
the risk of pregnancy.
- Males with female partners of child-bearing potential must agree to use
physician-approved contraceptive methods (e.g., abstinence, condoms,vasectomy)
throughout the study and should avoid donating sperm, for 90 days following the
last dose of study drug.
- Subjects who are currently taking the following concomitant medications:
- Anti-cancer Agents: Subjects who are currently receiving other anti-cancer agents
are not eligible.
- CYP3A4 Agents: Subjects who are currently receiving drugs that are strong
inducers or strong inhibitors of CYP3A4 are not eligible. Strong inducers or
inhibitors of CYP3A4 are prohibited from 14 days prior to the first dose of
Tazemetostat to the end of the study. Note: Dexamethasone for CNS tumors or
metastases, on a stable dose, is allowed.
- Subjects who are acutely ill with an uncontrolled active infection on systemic
anti-infective agents are not eligible.
- Subjects with a prior history of T-cell lymphoblastic lymphoma/T-cell acute
lymphoblastic leukemia or myelodysplastic syndrome (MDS).
- Subjects who have any of the following underlying major cardiac issues or conditions:
- Known QTc prolongation or documentation on screening ECG (QTcF interval on
screening ECG ≥ 480 milliseconds).
- Documented New York Heart Association (NYHA) Class III or IV congestive heart
- Myocardial infarction within 6 months prior to registration.
- Unstable angina within 6 months prior to registration.
- Symptomatic arrhythmia.
- Subjects who in the opinion of the investigator may be high risk for treatment
complications or unable to comply with the safety monitoring requirements of the study
- Heterosexually active males or females of reproductive potential may not participate
unless they have agreed to use two highly effective contraceptive methods for the
duration of study treatment.
- Females who are pregnant or breastfeeding
- Administration of a vaccine containing live virus within 30 days prior to the first
dose of trial treatment.
- Prisoners or subjects who are involuntarily incarcerated, or subjects who are
compulsorily detained for treatment of either a psychiatric or physical illness.