| Eligibility |
Inclusion Criteria:
- Documented informed consent of the participant and/or legally authorized
representative
- Age: >= 18 years
- Eastern Cooperative Oncology Group (ECOG) =< 2
- Histologically confirmed diagnosis of follicular lymphoma grade 1-3a according to the
World Health Organization (WHO) classification, with hematopathology review at the
participating institution
- Relapsed/ refractory disease after at least 2 lines of systemic therapy including an
anti-CD20 antibody. Relapse must have been confirmed histologically (with
hematopathology review at the participating institution). Exceptions may be granted
with study PI approval
- Active disease meeting requiring treatment per treating physician's decision
- Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy with one
or more sites of disease >= 1.5 cm in longest dimension
- Fully recovered from the acute toxic effects (except alopecia) to <= Grade 1 to prior
anti-cancer therapy
- Without bone marrow involvement: Absolute neutrophil count (ANC) >== 1,000/mm^3
- NOTE: Growth factor is not permitted within 14 days of ANC assessment unless
cytopenia is secondary to disease involvement.
- With bone marrow involvement: ANC >= 500/mm^3
- NOTE: Growth factor is not permitted within 14 days of ANC assessment unless
cytopenia is secondary to disease involvement.
- Without bone marrow involvement: Platelets >= 50,000/mm^3
- NOTE: Platelet transfusions are not permitted within 7 days of platelet
assessment unless cytopenia is secondary to disease involvement.
- With bone marrow involvement: Platelets >= 30,000/mm^3
- NOTE: Platelet transfusions are not permitted within 7 days of platelet
assessment unless cytopenia is secondary to disease involvement.
- Hemoglobin >= 8 g/dL
- NOTE: No erythropoietin and/or packed red blood cells (pRBC) transfusion allowed
within 7 days prior to screening)
- Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease or
hepatic involvement by lymphoma)
- Aspartate aminotransferase (AST) =< 2.5 x ULN
- Alanine aminotransferase (ALT) =< 2.5 x ULN
- Creatinine clearance of >= 50 mL/min per 24 hour urine test or the Cockcroft-Gault
formula
- Women of childbearing potential (WOCBP): negative serum pregnancy test within 3 days
prior to cycle 1 day 1
- Agreement by females of childbearing potential* to use 2 reliable methods of
contraception simultaneously (including one highly effective and one effective
contraceptive method) and males (including those who have had a vasectomy) to use an
highly effective method of birth control, or abstain from heterosexual activity for
the course of the study starting from at least 28 days prior to initiating
tazemetostat for women, and 7 days prior to initiating tazemetostat for men, through
at least 6 months after the last dose of tazemetostat for women and 3 months for men,
and at least 4 months after the last dose of ublituximab or umbralisib, whichever
comes later, for both men and women
- Childbearing potential defined as not being surgically sterilized (women) or have
not been free from menses for > 1 year (women only).
Exclusion Criteria:
- Prior therapeutic intervention with any of the following: therapeutic anticancer
antibodies within 3 weeks (rituximab); radio- or toxin-immunoconjugates within 10
weeks; all other chemotherapy or radiation therapy within 3 weeks prior to day 1 of
protocol therapy.
- Prior exposure to either a PI3K inhibitor (including but not limited to idelalisib,
duvelisib, copanlisib, and umbralisib) or an EZH2 inhibitor (including but not limited
to tazemetostat).
- Prior allogeneic stem cell transplant
- Autologous hematologic stem cell transplant within 6 months of day 1 of protocol
therapy
- Major surgical procedure (under general anesthesia) within 30 days of Day 1 of
protocol therapy. Note: If a subject had major surgery, they must have recovered
adequately from any toxicity and/or complications from the intervention before the
first dose of study drug
- Chronic use of corticosteroids >= 20 mg/day of prednisone or equivalent (short-term
use of steroids < 14 days is allowed).
- Requires treatment with a strong or moderate cytochrome P450 3A4 (CYP3A4)
inhibitor/inducer
- Known history of hypersensitivity or anaphylaxis to study drug(s) including active
product or excipient components
- Concurrent participation in another therapeutic clinical trial
- History of prior malignancy. Exceptions include malignancy treated with curative
intent and no known active disease present for >= 2 years prior to initiation of
protocol therapy; adequately treated non-melanoma skin cancer or lentigo maligna
(melanoma in situ) without evidence of disease; adequately treated in situ carcinomas
(e.g., cervical, esophageal, etc.) without evidence of disease; asymptomatic prostate
cancer managed with "watch and wait" strategy.
- Prior history of myeloid malignancies including myelodysplastic syndrome (MDS) or
presence of cytogenetic and/or molecular abnormalities known to be associated with MDS
or myeloproliferative neoplasms (MPN) (e.g. del 5q, chr 7 abn, JAK2 V617). Any
evidence of clonal hematopoiesis in the screening bone marrow biopsy should be
discussed with the study principal investigator (PI) prior to enrollment
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel that is likely to affect absorption,
symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or
gastric restrictions and bariatric surgery, such as gastric bypass
- Known active central nervous system (CNS) involvement by lymphoma, including
leptomeningeal involvement
- Clinically significant cardiovascular disease such as symptomatic arrhythmias,
congestive heart failure, or myocardial infarction within 6 months of screening, or
any class III or IV cardiac disease as defined by the New York Heart Association
Functional Classification. Note Subjects with controlled, asymptomatic atrial
fibrillation can enroll on study.
- Inability to swallow and retain an oral medication
- Clinically significant uncontrolled illness, including active infection requiring
antibiotics
- Live virus vaccines within 4 weeks of start of protocol therapy or planned
administration of live virus vaccines during ublituximab therapy
- Evidence of chronic active hepatitis B (HBV, not including patients with prior
hepatitis B vaccination; or positive serum hepatitis B antibody) or chronic active
hepatitis C infection (HCV), or active cytomegalovirus (CMV). If hepatitis B virus
core (HBc) antibody is positive, the subject must be evaluated for the presence of HBV
deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR). If HCV antibody is
positive, the subject must be evaluated for the presence of HCV ribonucleic acid (RNA)
by PCR. If the subject is CMV IgG or CMV IgM positive, the subject must be evaluated
for the presence of CMV DNA by PCR. Subjects with positive HBc antibody and negative
HBV DNA by PCR are eligible. Subjects with positive HCV antibody and negative HCV RNA
by PCR are eligible. Subjects who are CMV IgG or CMV IgM positive but who are CMV DNA
negative by PCR are eligible. Patients with a prior known history of hepatitis B and
those with a positive anti-HBc with negative hepatitis B surface antigen (HBsAg) at
screening must be able to receive antiviral agents effective against hepatitis B such
as, but not limited to, enofovir or entecavir
- Known history of human immunodeficiency virus (HIV) infection
- Females only: Pregnant or breastfeeding
- Any other condition that would, in the Investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures.
- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)
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