| Eligibility |
Inclusion Criteria:
- Patients must have a confirmed diagnosis of one of Richter's transformation (to either
diffuse large B cell lymphoma (DLBCL) or Hodgkin's lymphoma) with preceding CLL/SLL
- Richter's transformation refers to development of aggressive lymphoma (most commonly
diffuse large B cell lymphoma (DLBCL), and less commonly Hodgkin's lymphoma) in a
patient who has a pre-existing diagnosis of CLL/SLL. A pathologic diagnosis of DLBCL
or Hodgkin's lymphoma in the setting of preceding CLL/SLL is required
- Patients with Richter's transformation arising from CLL/SLL may be newly diagnosed or
have relapsed or progressed after prior treatment. Patients with newly diagnosed
Richter transformation are eligible only if the treating physician believes they are
not good candidates for standard immunochemotherapy or chemotherapy
- All patients must have measurable disease as defined by Lugano criteria 2014
- Patients must be age = 18 years
- Patients must exhibit a/an Eastern Cooperative Oncology Group (ECOG) performance
status of 0-2
- Absolute neutrophil count = 1,000/mcL (independent of growth factor support for = 14
days) (within 14 days prior to registration)
- Platelets = 30,000/mcl (independent of transfusion for = 14 days) (within 14 days
prior to registration)
- Hemoglobin = 8 g/dL (within 14 days prior to registration)
- Note: patients must be able to maintain this level without transfusion
- Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (within 14 days
prior to registration)
- Note: Autoimmune hemolytic anemia (AIHA) and Gilbert's syndrome are exceptions
and bilirubin value must be < 5 x ULN
- Aspartate aminotransferase (AST) ( serum glutamic-oxaloacetic transaminase [SGOT]) =
1.5 X ULN (within 14 days prior to registration)
- Alanine transaminase (ALT) (serum glutamic-pyruvic transaminase [SPGT]) = 1.5 X ULN
(within 14 days prior to registration)
- Creatinine clearance = 50mL/min (within 14 days prior to registration)
- Calculate creatinine clearance (CrCl) using the Cockcroft Gault
- Patients with a known history chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
- Patients with a known history of hepatitis C (HCV) infection must have been treated
and cure. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Females of child-bearing potential (FOCBP) must agree to adequate contraception
(abstinence or acceptable methods of birth control such as barrier method or hormonal
contraception) with partner(s) for the duration of study participation, for 5 months
after the last dose of nivolumab and 12 months after the last dose of rituximab
following completion of therapy.
- NOTE: A FOCBP is any woman (regardless of sexual orientation, including women who
having undergone a tubal ligation, or remaining celibate by choice) who meets the
following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy
- Has had menses at any time in the preceding 12 consecutive months (and therefore
has not been naturally postmenopausal for > 12 months; confirmation of
postmenopausal state will be done by clinical history of last menstrual period)
- FOCBP must have a negative urine or serum pregnancy test within 7 days prior to
registration on study.
- NOTE: Patients are also required to have a negative pregnancy test within 24
hours of first dose of study drug
- Patients must have the ability to understand and the willingness to sign a written
informed consent prior to registration on study
- Patients must have the ability to swallow and maintain oral medication
- Patients must be willing and able to start treatment with allopurinol or equivalent =
3 days prior to starting treatment with venetoclax
Exclusion Criteria:
- Patients who have received prior nivolumab for treatment of Richter's transformation,
or other PD-1/PD-L1 for the treatment of any indication.
- Note: Prior anti-CD-20 antibody treatment is allowed with = 14 day washout
period. Prior treatment with nivolumab is permissible if for a different disease
indication. In such cases nivolumab must have been discontinued = 3 months prior
to registration
- Patients who have a history of life-threatening adverse reactions attributed to
compounds of similar chemical or biologic composition to venetoclax, nivolumab, or
rituximab
- Patients who are refractory to venetoclax (defined by disease progression while on
venetoclax or within 3 months of discontinuing venetoclax)
- Patients who have had prior chimeric antigen receptor-modified T-cell (CAR-T) therapy
within the 45 days prior to registration or with any remaining CAR-T related
cytokine-release syndrome or neurotoxicity
- Patients who have adverse events due to agents administered = 30 days prior to
registration that have not recovered to = grade 2
- Patients who have had chemotherapy, radiotherapy or immunotherapy = 14 days prior to
registration
- Patients receiving any other investigational agents within = 30 days or 5 half-lives
prior to registration, whichever is shorter
- Patients who have received B-cell receptor pathway inhibitor (such as ibrutinib or
idelalisib) = 3 days prior to receiving study treatment
- Patients who have undergone an autologous stem cell transplant = 120 days prior to
registration
- Patients who have undergone an allogeneic stem cell transplant = 180 days prior to
registration.
- Note: Patients must be off all immunosuppressive therapies > 30 days prior to
registration, with no active graft versus host disease (GVHD)
- Patients with acute or extensive chronic graft-versus-host disease (GVHD)
- Patients who have received any of the following agents = 7 days prior to receiving
study treatment:
- Steroid therapy with anti-neoplastic intent
- Moderate or strong CYP3A inhibitors
- Moderate or strong CYP3A inducers
- Patients who have received a live / attenuated vaccine = 30 days prior to receiving
study treatment
- Patients who have history of auto-immune conditions requiring ongoing or intermittent
systemic treatment in the past 2 years (i.e., with use of disease modifying agents,
corticosteroids or immunosuppressive medications)
- Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.)
is not considered a form of systemic treatment
- Patients who have a history of active malignancy other than CLL/SLL or RT within the
past 2 years, with the exception of:
- Adequately treated in situ carcinoma of the cervix uteri
- Adequately treated basal cell carcinoma or localized squamous cell carcinoma of
the skin
- Previous malignancy confined and surgically resected (or treated with other
modalities) with curative intent
- Patients who have known autoimmune disease or active uncontrolled autoimmune
cytopenias
- Patients who have overt thyroid dysfunction (hyperthyroidism or hypothyroidism).
- Note: Patients with chronic hypothyroidism taking stable dose of thyroid
replacement therapy with normal TSH are eligible
- Patients with systemic fungal, bacterial, viral, or other infection that is not
controlled (defined as exhibiting ongoing signs/symptoms related to the infection and
without improvement, despite appropriate antibiotics or other treatment
- Any patient who has tested positive for human immunodeficiency virus (HIV) (due to
potential drug-drug interactions between anti-retroviral medications and venetoclax,
as well as anticipated venetoclax mechanism based lymphopenia that may potentially
increase the risk of opportunistic infections).
- Note: HIV test is not a requirement to determine eligibility
- Patients who have malabsorption syndrome or another condition that precludes enteral
route of administration
- Patients with a known contraindication or allergy to both xanthine oxidase inhibitors
and rasburicase
- Patients who have a significant history of cardiovascular, pulmonary, renal, hepatic,
neurologic, psychiatric, endocrinologic, metabolic, or immunologic disease that in the
opinion of the investigator would adversely affect his/her participation in this study
or interpretation of study results
- Patients who are pregnant or nursing
|
