| Eligibility |
Inclusion Criteria:
- Documented informed consent of the participant and/or legally authorized
representative
- Assent, when appropriate, will be obtained per institutional guidelines
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- If unavailable, exceptions may be granted with study principal investigator (PI)
approval
- Age: >= 18 to 80 years
- Eastern Cooperative Oncology Group =< 2
- Diagnosis of MCL established by histologic assessment including one of the following:
- Immunohistochemistry of the biopsy
- Flow cytometry of the biopsy
- Evidence of t(11;14) translocation involving the cyclin D1 gene by fluorescence in
situ hybridization (FISH), and/or cyclin D1 expression by immunohistochemistry (IHC)
unless disease is morphologically consistent with MCL and has IHC expression of SOX11
- Requiring treatment for MCL, and for which no prior systemic anticancer therapies have
been received
- Local radiotherapy not exceeding a total dose of 20 Gy at least 2 weeks prior the
first dose of study therapy is allowed
- Laboratory, radiographic, physical exam findings and/or symptoms attributable to MCL
- Asymptomatic patients with blastoid or pleomorphic variant can be enrolled
- High risk features as classified by Jain et al.
- Blastoid/pleomorphic variants
- Ki67 >= 50%
- Presence of a TP53 mutation defined by either molecular testing or IHC
- del (17p) by FISH
- Complex karyotype
- High-risk Mantle Cell Lymphoma International Prognostic Index (MIPI) score (>=
6.2)
- Bulky disease
- The presence of other high risk gene mutations (KMT2D, NSD2, NOTCH1, CDKN2A,
NOTCH2, SMARCA4, CCND1) as long one of the other features above are present
- Ability to swallow oral capsules/tablets
- Without bone marrow involvement: absolute neutrophil count (ANC) >= 1,000/mm^3 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 >= 75,000/mm^3 With bone marrow
involvement: Platelets >= 25,000/mm^3
- NOTE: Platelet transfusions are not permitted within 14 days of platelet
assessment unless cytopenia is secondary to disease involvement
- Without bone marrow involvement: Hemoglobin >= 8 g/dL With bone marrow involvement:
Hemoglobin >= 7 g/dL
- NOTE: Red Blood cells transfusions are not permitted within 14 days of hemoglobin
assessment unless cytopenia is secondary to disease involvement
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease)
- Aspartate aminotransferase (AST) =< 3.0 x ULN
- Alanine aminotransferase (ALT) =< 3.0 x ULN
- Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault
formula
- If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin
(PT) =< 1.5 x ULN If on anticoagulant therapy: PT must be within therapeutic range of
intended use of anticoagulants
- If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x
ULN If on anticoagulant therapy: aPTT must be within therapeutic range of intended use
of anticoagulants
- Women of childbearing potential (WOCBP): negative serum pregnancy test
- Agreement by females and males of childbearing potential to use an effective method of
birth control (i.e., failure rate of < 1% per year) or abstain from heterosexual
activity for the course of the study treatment period through at least 30 days after
the last dose of venetoclax and lenalidomide, 18 months after the last dose of
obinutuzumab, 2 months after the last dose of glofitamab, or 4 months after the last
dose of tocilizumab (if applicable) whichever is longer
- Childbearing potential defined as not being surgically sterilized (men and women)
or have not been free from menses for > 1 year (women only).
- All study participants must be registered into the mandatory Revlimid Risk
Evaluation and Mitigation Strategy (REMS) (registered trademark) program and
be willing and able to comply with the requirements of the REMS (registered
trademark) program (including use of aspirin [ASA]/ Food and Drug
Administration [FDA] approved blood thinner)
- Females of reproductive potential must adhere to the scheduled pregnancy
testing as required in the Revlimid REMS (registered trademark) program
Exclusion Criteria:
- Treatment with the use of warfarin (because of potential drug-drug interactions that
may potentially increase the exposure of warfarin)
- Treatment with strong or moderate CYP3A inhibitors or strong CYP3A inducers within 4
weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of
study drug. Consumed grapefruit, grapefruit products, Seville oranges (including
marmalade containing Seville oranges), or star fruit within 3 days prior to first dose
of venetoclax
- Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Patients who
received corticosteroid treatment with =< 30 mg/day of prednisone or equivalent must
be documented to be on a stable dose of at least 4 weeks' duration prior to day 1 of
cycle 1. Patients may have received a brief (=< 7 days) course of systemic steroids
(>= 100 mg prednisone equivalent per day) prior to initiation of study therapy for
control of lymphoma-related symptoms
- Corticosteroid therapy for control of cancer symptoms is permitted
- The use of inhaled corticosteroids is permitted
- The use of mineralocorticoids for management of orthostatic hypotension is
permitted
- The use of physiologic doses of corticosteroids for management of adrenal
insufficiency is permitted
- Illicit drug or alcohol abuse within 12 months prior to screening, in the
investigator's judgment
- Prior solid organ transplantation within 60 months and requiring active
immunosuppression
- Receipt of live-virus vaccine within 28 days prior to the initiation of the study
treatment or need for live-virus vaccines at any time during the study treatment
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to study agents
- History of other malignancy that could affect compliance with the protocol or
interpretation of results
- Patients with a history of curatively treated basal or squamous cell carcinoma of
the skin or in situ carcinoma of the cervix are generally eligible
- Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below,
stage 1 or 2) with no requirement for therapy at any time prior to study are
eligible
- Patients with any other malignancy appropriately treated with curative intent and
the malignancy has been in remission without treatment for >= 2 years prior to
enrollment are eligible
- Patients receiving adjuvant endocrine therapy for non-metastatic, hormone
receptor positive breast cancer for >= 2 years prior to enrollment are eligible
- Major surgery (within 4 weeks prior to the start of the first dose of study
treatment), other than for diagnosis
- Known or suspected chronic active Epstein-Barr viral infection
- Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
- Known history of progressive multifocal leukoencephalopathy
- Malabsorption syndrome or other condition that precludes enteral route of
administration
- Known allergy to both xanthine oxidase inhibitors and rasburicase
- Positive for hepatitis C virus (HCV) virus by polymerase chain reaction (PCR) at
screening. Testing only required if the hepatitis (Hep) C antibody is positive
- Positive test results for hepatitis B virus (HBV) infection (defined as positive
surface antigen [HBsAg]) at screening
- Patients with occult or prior HBV infection (defined as negative HBsAg and
positive hepatitis B core antibody [HBcAb]) may be included if HBV
deoxyribonucleic acid (DNA) is undetectable, if they are willing to undergo DNA
testing on day 1 of every cycle and every three months for at least 12 months
after the last cycle of study treatment and appropriate antiviral therapy
- Known active human immunodeficiency virus (HIV) infection. Subjects who have an
undetectable or unquantifiable HIV viral load with CD4 > 200 and are on highly active
antiretroviral therapy (HAART) medication are allowed. Testing to be done only in
patients suspected of having infections or exposures
- Significant or extensive cardiovascular disease such has New York Heart Association
class III or IV cardiac disease or Objective Assessment class C or D, myocardial
infarction within the last 6 months, unstable arrythmias or unstable angina
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) at study enrollment or any major episode of
infection (as evaluated by the investigator) within 4 weeks prior to the first study
treatment
- Suspected or latent tuberculosis (confirmed by positive interferon -gamma release
assay)
- Females only: Pregnant or breastfeeding or intending to become pregnant during the
study or within 18 months after the final dose of all study drugs
- Women of childbearing potential must have a negative serum pregnancy test result
within 14 days prior to initiation of study drug
- History of uncontrolled autoimmune condition or disease requiring active systemic
treatment to manage except when on a stable regimen for the treatment of
hypothyroidism, Type 1 diabetes mellitus or psoriasis/eczema (topicals only)
- Patients with history of immune thrombocytopenic purpura, autoimmune hemolytic
anemia, Guillain-Barre syndrome, myasthenia gravis, myositis, rheumatoid
arthritis, vasculitis, or other autoimmune disease will be excluded unless they
have not required systemic therapy in the last 12 months
- Prior treatment with systemic immunosuppressive medications (including, but not
limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-tumor necrosis factor agents), within 4 weeks prior to first dose of study
treatment
- Patients with a history of autoimmune hepatitis, systemic lupus erythematosus,
inflammatory bowel disease with active symptoms within last 60 months and on
active immunosuppressive therapy, vascular thrombosis associated with
antiphospholipid syndrome, Wegener granulomatosis, Sjogren syndrome, multiple
sclerosis, or glomerulonephritis will be excluded
- Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment
or history of CNS lymphoma
- Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or
neurodegenerative disease
- Patients with a history of stroke who have not experienced a stroke or transient
ischemic attack within the past 9 months and have no residual neurologic
deficits, as judged by the investigator, are allowed
- Clinically significant history of cirrhotic liver disease
- 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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