| Eligibility |
Inclusion Criteria:
1. Male = 18 years of age at time of consent
2. Female = 18 years of age at time of consent and of non-childbearing potential. A woman
is considered to be of non-childbearing potential if she has reached a postmenopausal
state (= 12 continuous months of amenorrhea with no identified cause other than
menopause) or has undergone surgical sterilization (removal of ovaries and/or uterus).
Note: Postmenopausal state will be confirmed with FSH test completed during the
screening period.
3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
4. Has a life expectancy of >3 months
5. Has EITHER histologically confirmed B-cell lymphomas including but not limited to
diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), primary mediastinal
B-cell lymphoma (PMBCL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), or
Hodgkin lymphoma (HL) and has relapsed or refractory disease following at least two
lines of prior standard therapy, including alkylator/anthracycline (unless
anthracycline-based chemotherapy is contraindicated)/anti-CD20-based therapy (R-CHOP,
rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone or
dexamethasone, or equivalent for non-Hodgkin lymphoma), AND must be considered unable
to benefit from intensification treatment with autologous hematopoietic stem cell
transplantation (ASCT) , as defined by meeting at least one of the following criteria:
- Relapsed following, or refractory to, previous ASCT
- Did not achieve at least a partial response to a standard salvage regimen (e.g.,
R-ICE, rituximab, ifosfamide, carboplatin, etoposide, or R-DHAP, rituximab,
dexamethasone, cytarabine, cisplatin)
- Ineligible for intensification treatment due to age or significant comorbidity
- Ineligible for intensification treatment due to failure to mobilize an acceptable
number of hematopoietic stem cells
- Refused intensification treatment and/or ASCT
OR
6. Histologically and/or cytologically confirmed advanced or metastatic solid tumor that
has progressed after treatment with approved therapies or for which there are no
standard therapies available
7. May have evaluable or measurable disease
8. Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related
clinically significant toxicities resolve to = Grade 1 per CTCAE, version 4.03 or are
clinically stable, at time of consent
9. Time between the last dose of the latest therapy and the first dose of study drug:
1. Chemotherapy: cytotoxic - at least 21 days
2. Chemotherapy: nitrosureas - at least 6 weeks
3. Chemotherapy: non-cytotoxic (e.g. small molecule inhibitor) - at least 14 days
4. Monoclonal antibody (ies) - at least 28 days
5. Immunotherapy (e.g. tumor vaccine) - at least 28 days
6. Radiotherapy (RT) - at least 21 days for stereotactic radiosurgery, at least 12
weeks for craniospinal, =50% radiation of pelvis, or total body irradiation
7. High dose therapy with autologous hematopoietic cell infusion - at least 60 days
8. Hematopoietic growth factor - at least 14 days
10. Has adequate hematologic (bone marrow [BM] and coagulation factors), renal and hepatic
function as defined by criteria below:
1. Hemoglobin =9 g/dL
2. Platelet =75,000/mm3 (=75 × 10^9/L)
3. ANC =750/mm3 (=0.75 × 10^9/L)
4. PT< 1.5 ULN
5. PTT< 1.5 ULN
6. Creatinine < 2.0 ULN
7. Conjugated bilirubin < 1.5 × ULN
8. AST <3 × ULN I. ALT <3 × ULN NOTE: Laboratory results obtained during screening
should be used to determine eligibility criteria. In situations where laboratory
results are outside the permitted range, the investigator may retest the subject
and the subsequent within range screening result may be used to determine the
subject's eligibility
11. Subjects with a history of Hepatitis B or C are eligible on the condition that
subjects have adequate liver function as defined the protocol and are hepatitis B
surface antigen negative and/or have undectable HCV RNA.
12. Has a QT interval corrected by Fridericia's formula (QTcF) =480 msec
13. Subject must have regular bowel movements (minimum of 1 bowel movement every day or
every other day; no more than 3 bowel movements per day) for the past 2 weeks without
diarrhea (>4 bowel movements per day) or constipation (fewer than 3 bowel movements in
1 week). No known medical history of a disease or syndrome that affects bowel function
(e.g., irritable bowel syndrome, inflammatory bowel disease, ulcerative colitis,
etc.), fecal incontinence, and no history of significant opioid induced constipation
within the past 3 months
14. Subject must have the ability to regularly void urine with no current evidence of
urinary incontinence, urinary retention, uncorrected congenital defects that interfere
with normal urinary system function, chronic urinary tract infections, or other
conditions that may interfere with normal urinary bladder emptying. In the past 3
months, no obstructive uropathy, surgery affecting urinary system (e.g., radical
prostatectomy, TURP, etc.), urinary tract infection. Subjects with solitary kidney are
excluded from the study
15. Male subjects must refrain from donating sperm starting at the planned first dose of
study drug until 30 days following the last dose of study drug. Male subjects with a
female partner of childbearing potential must be vasectomized, or remain abstinent or
use a condom as defined in Section 8.3.8, starting at the planned first dose of study
drug until 30 days following the last dose of study drug. The reliability of sexual
abstinence should be evaluated in relation to the duration of the clinical trial and
the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar,
ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable
methods of contraception. Female partners of male subjects who are of childbearing
potential must also adhere to one of the following:
- Placement of an intrauterine device or intrauterine system.
- Established use of oral, injected or implanted hormonal methods of contraception.
- Progesterone only oral contraception, where inhibition of ovulation is not the
primary mode of action.
Exclusion Criteria:
Subjects meeting ANY of the following criteria must NOT be enrolled in this study:
1. Has participated in a study in which [14C] was administered within the last 6 months
prior to screening for this study
2. Has CNS or leptomeningeal metastasis
3. Has had a prior malignancy other than the malignancies under study Exception: Subject
who has been disease-free for 3 years, or a subject with a history of a completely
resected non-melanoma skin cancer or successfully treated in situ carcinoma are
eligible
4. Has had major surgery within 3 weeks prior to enrollment NOTE: Minor surgery (e.g.,
minor biopsy, central venous catheter placement) is permitted within 3 weeks prior to
enrollment
5. Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet
and all foods that contain those fruits from time of enrollment to while on study
6. Has cardiovascular impairment, history of congestive heart failure greater than NYHA
Class II uncontrolled arterial hypertension, unstable angina, myocardial infarction,
or stroke within 6 months prior to the planned first dose of tazemetostat; or
ventricular cardiac arrhythmia requiring medical treatment
7. Subjects taking medications that are known potent CYP3A4 inducers/inhibitors
(including St. John's Wort) from 14 days prior to the first dose of study medications
(see
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteracti
onsLabeling/ucm080499.htm; or http://medicine.iupui.edu/clinpharm/ddis/ for a list of
potent CYP3A4 inducers and inhibitors).
8. Has an active infection requiring systemic treatment
9. Is immunocompromised, including subjects with known history of infection with human
immunodeficiency virus (HIV)
10. Has known history of chronic infection with hepatitis B virus (hepatitis B surface
antigen positive) or hepatitis C virus (detectable HCV RNA)
11. Has had a venous thrombosis or pulmonary embolism within the 3 months prior to study
enrollment.
NOTE: Subjects with a history of a deep vein thrombosis >3 months prior to study
enrollment who are on anticoagulation therapy with low molecular weight heparin are
eligible for this study.
12. Has known hypersensitivity to any of the components of study drug
13. Is unable to take oral medications, malabsorption syndrome or any other uncontrolled
gastrointestinal condition (e.g., nausea, diarrhea or vomiting) that might impair the
bioavailability of study drug
14. Has an uncontrolled intercurrent illness including, but not limited to, uncontrolled
infection, or psychiatric illness/social situations that would limit compliance with
study requirements
15. Is unwilling to adhere to contraception criteria from time of enrollment in study to
at least 30 days after last dose of study drug
16. Clinical history, current alcohol (ethanol), or illicit drug use which, in the
judgment of the investigator, will interfere with the subject's ability to comply with
the dosing schedule and protocol-specified evaluations
17. A history of bleeding (i.e., hemoptysis, hematuria, GI blood loss, epistaxis, or
others with greater than Grade 1 according to National Cancer Institute Common
Terminology Criteria Version 4.0 [NCI-CTC v4.0]) within 1 month prior to beginning
therapy or any clinical indications of current active bleeding
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