Inclusion Criteria:
- Patients ≥ 18 years of age with any of the following: Histopathologically confirmed
DLBCL or HGBL (i.e., HGBL with MYC, BCL2, and/or BCL6 rearrangements, HGBL, not
otherwise specified [NOS], or DLBCL, NOS) that is refractory to, or has relapsed
after, treatment with at least 1 prior regimen. Eligible sub-types include DHL, THL,
or DEL, as well as DLBCL or HGBL without MYC and/or BCL2 alterations. Criteria for DHL
are concurrent MYC translocation+ and BCL2 translocation+ by fluorescence in situ
hybridization (FISH) (same criteria for THL, which also includes BCL6 translocation+
by FISH); criteria for DEL are concurrent overexpression of MYC (≥ 40%) and BCL2 (>
50%) by immunohistochemistry (IHC).
- Measurable disease by CT or PET/CT. MRI acceptable as per protocol.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Recovery to Grade 1 or baseline of any toxicity due to prior systemic treatments
(excluding alopecia).
- Absolute neutrophil count ≥ 1,000/µL; platelets ≥ 75,000/µL for patients with no bone
marrow involvement by malignancy; platelets ≥ 50,000/µL for patients with bone marrow
involvement by malignancy.
- Creatinine ≤ 1.5x upper limit of normal (ULN); total bilirubin ≤ 1.5x ULN; AST/ALT ≤
2.5x ULN.
- Life expectancy of at least 3 months.
Exclusion Criteria:
- Intention to undergo stem cell transplant (SCT) or treatment with chimeric antigen
receptor (CAR) T-cell therapy.
- SCT therapy within 100 days prior to starting study treatment.
- Systemic anti-cancer therapy or investigational agent within 3 weeks of study entry,
except for nitrosoureas or mitomycin C (6 weeks).
- Other non-cytotoxic anti-cancer therapy or investigational agent within 5 half-lives
or 21 days prior to study treatment, whichever is shorter, as long as any drug related
toxicities have resolved to Grade 1 or less. Dexamethasone up to 12 mg/d is allowed as
supportive therapy and does not exclude participation.
- Contraindication to venetoclax or rituximab.
- Progressive disease during treatment or within 3 months of stopping prior treatment
with a BCL2 inhibitor, histone deacetylase (HDAC) inhibitor, or phosphoinositide-3
kinase (PI3k) inhibitor, or prior discontinuation of any of these therapies due to
clinically significant toxicity.
- Graft vs. host disease following prior allogeneic transplant within 3 months prior to
study treatment.
- Ongoing treatment with chronic immunosuppressants.
- Active CNS lymphoma.
- Known gastrointestinal condition that would interfere with swallowing or the oral
absorption or tolerance of fimepinostat.
- Serious infection requiring systemic antibiotic therapy within 14 days prior to study
treatment.
- Uncontrolled or severe cardiovascular disease
- Unstable or clinically significant concurrent medical condition.
- Second primary malignancy within 2 years of study entry other than what is specified
in the protocol.
- Known HIV positive, hepatitis B surface antigen-positive status, or known or suspected
active hepatitis C infection.
- Active CMV infection, presence of CMV antigenemia, or evidence of any invasive CMV end
organ disease (e.g., CMV colitis).
