Inclusion Criteria:

- Age >= 18 years willing to provide consent and follow-up

- Diagnosis of CLL according to the International Workshop on Chronic Lymphocytic
Leukemia (IWCLL) 2018 criteria (Hallek et al., 2018) or small lymphocytic lymphoma
(SLL) according to the World Health Organization (WHO) 2008 criteria (Harris, 1999).
This includes previous documentation of:

- Biopsy-proven SLL according to WHO 2008 criteria, or

- Diagnosis of CLL according to IWCLL 2018 criteria as evidenced by all of the
following:

- Peripheral blood B cell count of >= 5 x 10^9/L consisting of small to
moderate size lymphocytes (If there are enough evidence to document the
prior diagnosis of CLL, it is not required to meet the criteria of
peripheral blood B cell count more than 5 x 10^9/L )

- Immunophenotyping consistent with CLL defined as:

- The predominant population of lymphocytes share both B-cell antigens
(CD19, CD20 [typically dim expression], or CD23) as well as CD5 in the
absence of other pan-T-cell markers (CD3, CD2, etc.)

- Clonality as evidenced by kappa or lambda light chain expression
(typically dim immunoglobulin expression) or other genetic method (e.g.
immunoglobulin heavy chain variable [IGHV] analysis)

- NOTE: Splenomegaly, hepatomegaly, or lymphadenopathy are not
required for the diagnosis of CLL

- Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by
demonstrating a negative fluorescence in situ hybridization (FISH) analysis
for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy or negative
immunohistochemical stains for cyclin D1 on involved tissue biopsy

- If prior CLL diagnosis was confirmed, or CLL diagnosis was confirmed on bone
marrow examination or tissue biopsy, peripheral blood B cell count less than
5 x 10^9/L is allowed

- Biopsy proven Richter's transformation of the CLL

- NOTE: Previously treated patients including CLL therapy can be enrolled. If
Richter's transformation (RT) developed from prior untreated CLL and has not
received any RT directed therapy, then patient is not eligible

- Richter patients with prior or concurrent CLL diagnosis and do not have other option
for standard therapy per treating physician's discretion

- Measurable disease can be detected in positron emission tomography (PET) or computed
tomography (CT) (>= 1 cm in diameter)

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

- Absolute neutrophil count >= 0.7 x 10^9/L unless marrow was involved by CLL or RT,
then absolute neutrophil count (ANC) >= 0.3 x 10^9/L (=< 14 days prior to
registration)

- Platelet count >= 40 x 10^9/L unless marrow was involved by CLL or RT, then platelet
>= 30 x 10^9/L without transfusion =< 1 week prior to study registration (=< 14 days
prior to registration)

- Hemoglobin (Hgb) >= 8 unless marrow was involved by CLL or RT, then Hgb >= 7 without
transfusion =< 1 week prior to study registration (=< 14 days prior to registration)

- Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to confirmed Gilbert's
disease (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated
in the absence of hemolysis or hepatic pathology), who will be allowed only in
consultation with their physician (=< 14 days prior to registration)

- Note: If total bilirubin is > 1.5 x ULN, a direct bilirubin should be performed
and must be =< upper limit of normal

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or
alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X
ULN unless liver metastases are present, in which case it must be =< 5 x ULN (=< 14
days prior to registration)

- Calculated creatinine clearance of > 30 mL/min by the Cockcroft-Gault formula
(Cockcroft and Gault 1976) (=< 14 days prior to registration)

- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

- NOTE: The following restrictions apply while the patient is receiving study
treatment and for the specified times before and after:

- Female patient of child-bearing potential

- Female patients of childbearing potential who are not abstinent and
intend to be sexually active with a non sterilized male partner must
use at least 1 highly effective method of contraception from the time
of screening throughout the total duration of the drug treatment and
the drug washout period (180 days after the last dose of study
treatment). Non-sterilized male partners of a female patient of
childbearing potential must use male condom plus spermicide throughout
this period. Cessation of birth control after this point should be
discussed with a responsible physician. Periodic abstinence, the rhythm
method, and the withdrawal method are not acceptable methods of birth
control. Female patients should also refrain from breastfeeding
throughout this period

- Male patients with a female partner of childbearing potential

- Non-sterilized male patients who are not abstinent and intend to be
sexually active with a female partner of childbearing potential must
use a male condom plus spermicide from the time of screening throughout
the total duration of the drug treatment and the drug washout period
(180 days after the last dose of study treatment). However, periodic
abstinence, the rhythm method, and the withdrawal method are not
acceptable methods of contraception. Male patients should refrain from
sperm donation throughout this period

- Female partners (of childbearing potential) of male patients must also use a
highly effective method of contraception throughout this period

- Females of childbearing potential are defined as those who are not
surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy,
or complete hysterectomy) or post-menopausal

- Women will be considered post-menopausal if they have been amenorrheic for
12 months without an alternative medical cause. The following age-specific
requirements apply:

- Women < 50 years of age would be considered post-menopausal if they
have been amenorrheic for 12 months or more following cessation of
exogenous hormonal treatments and if they have luteinizing hormone and
follicle-stimulating hormone levels in the post-menopausal range for
the institution

- Women >= 50 years of age would be considered post-menopausal if they
have been amenorrheic for 12 months or more following cessation of all
exogenous hormonal treatments, had radiation-induced menopause with
last menses > 1 year ago, had chemotherapy-induced menopause with last
menses > 1 year ago

- Highly effective methods of contraception, defined as one that results in a
low failure rate (i.e., less than 1% per year) when used consistently and
correctly are described below. Note that some contraception methods are not
considered highly effective (e.g. male or female condom with or without
spermicide; female cap, diaphragm, or sponge with or without spermicide;
non-copper containing intrauterine device; progestogen-only oral hormonal
contraceptive pills where inhibition of ovulation is not the primary mode of
action [excluding Cerazette/desogestrel which is considered highly
effective]; and triphasic combined oral contraceptive pills)

- Effective methods include:

- Copper T intrauterine device

- Levonorgestrel-releasing intrauterine system (e.g., Mirena)

- Implants: Etonogestrel-releasing implants: e.g. Implanon or Norplant

- Intravaginal: Ethinylestradiol/etonogestrel-releasing intravaginal
devices: e.g. NuvaRing

- Injection: Medroxyprogesterone injection: e.g. Depo-Provera

- Combined pill: Normal and low dose combined oral contraceptive pill

- Patch: Norelgestromin/ethinylestradiol-releasing transdermal system:
e.g. Ortho Evra

- Minipill: Progesterone based oral contraceptive pill using desogestrel:
Cerazette is currently the only highly effective progesterone-based

- Tubal ligation

- Provide informed written consent

- Willing to return to Mayo Clinic enrolling institution for follow-up

- Willing to provide tissue, blood, and bone marrow samples for mandatory correlative
research purposes

Exclusion Criteria:

- Any of the following uncontrolled intercurrent illness:

- Clinically significant cardiovascular disease such as:

- Symptomatic arrhythmias

- Congestive heart failure

- Myocardial infarction =< 3 months prior to registration

- Any class 3 or 4 cardiac disease as defined by the New York Heart
Association functional classification

- Uncontrolled hypertension

- Unstable angina pectoris

- Note: Subjects with controlled, asymptomatic atrial fibrillation can
enroll on study

- Serious chronic gastrointestinal conditions associated with diarrhea

- History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)

- History of stroke or intracranial hemorrhage within 6 months before first dose of
study drug

- History of bleeding diathesis (e.g., hemophilia, von Willebrand disease)

- Active uncontrolled infection (e.g., bacterial, viral or fungal, including
subjects with positive cytomegalovirus [CMV] deoxyribonucleic acid [DNA]
polymerase chain reaction [PCR]) requiring systemic therapy. NOTE: When the
infection is controlled with systemic therapy, patients are permitted for this
study

- Active tuberculosis infection (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis [TB]
testing in line with local practice)

- Known human immunodeficiency virus (HIV/acquired immunodeficiency syndrome
[AIDS]) infection as further severe immunosuppression with this regimen may occur

- Hepatitis B or C serologic status:

- Hepatitis B surface antigen and hepatitis B PCR positive will be excluded

- Hepatitis B core antibody (anti-HBc) positive and who are surface antigen
negative, and hepatitis B PCR positive will be excluded

- These above patients once treated for hepatitis B and became hepatitis B PCR
negative, they will be eligible

- Hepatitis C PCR positive will be excluded. Once treated and hepatitis C PCR
negative will be eligible

- NOTE: Once patients with active hepatitis treated with effective therapy and
adequate disease control, they will be allowed for participation

- Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
unknown

- Pregnant women

- Nursing women

- Men and women of childbearing potential who are unwilling to employ highly
effective method of contraception starting with the screening visit through 180
days after the last dose of trial treatment

- Treated with other active investigational agents (excluding venetoclax, acalabrutinib.
or ibrutinib) =< 5 half -lives of the previous investigational agents, please consult
study chair for the specific investigational agent

- Prior durvalumab treatment. Note: If patients were treated with other prior PD1
blockade or PDL1 blockade, they will still be eligible

- Active or recent (=< 2 months) documented autoimmune or inflammatory disorders
(including inflammatory bowel disease [e.g., colitis or Crohn's disease],
diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus,
Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves'
disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]) not being controlled.
Exceptions:

- Patients with vitiligo or alopecia

- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement

- Any chronic skin condition that does not require systemic therapy

- Patients without active disease in the last 3 years may be included but only
after consultation with the study physician

- Patients with celiac disease controlled by diet alone

- Evidence of interstitial lung disease or active, non-infectious pneumonitis

- Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial

- Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with
malignant lymphoma cells that requires therapy

- Clinically significant coagulopathy per investigator's assessment (stable
anticoagulation except warfarin or other vitamin K antagonist will be allowed)

- Received an allogenic stem cell transplant within the last 2 years; Or prior history
of allogeneic stem cell transplant with history of graft versus host disease (GVHD)

- Active chronic GVHD requiring treatment

- Chronically taking a strong CYP3A inhibitor or inducer and moderate inducer and cannot
be switched to an alternative agent at least 4 days prior to trial therapy initiation
that in the opinion of investigator/treating physicians precludes utilization of trial
therapy

- Patients taking proton pump inhibitor will be excluded. NOTE: Patient may be switch to
an H2 blocker or antiacid

- History of another primary malignancy except for:

- Malignancy treated with curative intent and with no known active disease >= 5
years before the first dose of study drug and of low potential risk for
recurrence

- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease

- Adequately treated carcinoma in situ without evidence of disease

- Indolent malignancy with expected life expectancy more than 2 years

- Current or prior use of immunosuppressive medication =< 5 half-lives of previous
immunosuppressive medication. The following are exceptions to this criterion:

- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)

- Systemic corticosteroids at physiologic doses not to exceed =< 30 mg/day of
prednisone or its equivalent

- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)

- Receipt of live attenuated vaccine =< 30 days prior to registration. Note:
Patients, if enrolled, should not receive live vaccine whilst receiving
investigational product (IP) and up to 30 days after the last dose of IP

- Any radiation therapy =< 1 week prior to registration

- Any major surgery =< 28 days prior to registration (Note: Routine tissue or nodal
biopsy or small procedures typically heal fast will not be counted as surgery)

- Body weight =< 30 kg

- Life expectancy < 12 weeks

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 7/17/23. Questions regarding updates should be directed to the study team contact.