| Eligibility |
Inclusion Criteria:
- Written informed consent. Participant or legally authorized representative (LAR) must
provide written informed consent prior to any study-specific procedures or
interventions
- Age >= 18 years. All genders, races, and ethnic groups will be included
- Ability to swallow and retain oral medication
- Documented previously untreated CLL. Diagnosis must be confirmed by peripheral flow
cytometry and made in accordance with international workshop (iw)CLL diagnostic
criteria
- Baseline detectable immunoglobulin heavy (IGH) gene signature determined as part of
clonoSEQ for minimal residual disease (MRD) testing
- Must meet at least 1 criterion for treatment based on iwCLL guidelines
- Evidence of progressive marrow failure as manifested by the onset or worsening of
anemia and/or thrombocytopenia, or
- Massive (i.e., lower edge of spleen >= 6 cm below the left costal margin),
progressive, or symptomatic splenomegaly, or
- Massive (i.e., >= 10 cm in the longest diameter), progressive, or symptomatic
lymphadenopathy, or
- Progressive lymphocytosis in the absence of infection, with an increase in blood
absolute lymphocyte count (ALC) > 50% over a 2 month period, or lymphocyte
doubling time of < 6 months (as long as initial ALC was >= 30,000/uL), or
- Autoimmune anemia and / or thrombocytopenia that is poorly responsive to
corticosteroids or other standard therapy, or
- Constitutional symptoms, defined as any one or more of the following disease
related symptoms or signs occurring in the absence of evidence of infection:
- Unintentional weight loss of >= 10% within the previous 6 months, or
- Significant fatigue (grade >= 2), or
- Fevers > 100.5°F or 38.0°C for >= 2 weeks, or
- Night sweats for > 1 month
- Presence of measurable lymphadenopathy, defined as the presence of > 1 nodal
lesion that measures > 2.0 cm in the longest diameter (LD) and > 1.0 cm in the
longest perpendicular diameter (LPD) as assessed by computed tomography (CT) or
magnetic resonance imaging (MRI)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of greater than 12 months, as estimated by the treating physician or
investigator
- Absolute neutrophil count (ANC) > 1,000/mm^3 (uL)
- Platelet count > 50,000/mm^3 (uL).
- Serum creatinine =< 2 x upper limit of normal (ULN) or creatinine clearance (CrCl) >=
40 mL/min by Cockcroft-Gault
- Aspartate aminotransferase (AST) =< 3 x ULN
- Alanine aminotransferase (ALT) =< 3 x ULN
- Alkaline phosphatase (ALP) =< 3 x ULN
- Total bilirubin =< 2.5 x ULN unless documented history of Gilbert's syndrome
- Negative for hepatitis C infection and chronic hepatitis B infection
- Participants with positive serology for hepatitis C virus (HCV) must have been
tested for HCV ribonucleic acid (RNA) and are eligible only in the case of
negative HCV RNA by polymerase chain reaction (PCR) testing
- Participants must be hepatitis B virus (HBV) negative by serology. Participants
with occult or prior HBV infection (defined as negative hepatitis B [HB] surface
antigen [sAg] and positive serology testing for anti-HBV core antigen [cAb]) may
be included if HBV deoxyribonucleic acid (DNA) was undetectable by PCR, provided
that they are willing to undergo monthly ongoing DNA testing. Antiviral
prophylaxis may be administered as per institutional guidelines
- Participants who have protective HBV titers of HB surface antibody (sAb) (HBsAb
positive, HBcAb negative, and HBsAg negative) after vaccination or previously
cured hepatitis B are eligible
- Individuals with childbearing potential must have documented negative pregnancy test
at least 7 days prior to start of any treatment drug and must commit to the use of
study approved methods of contraception during study treatment and for 6 months after
the last dose of obinutuzumab
- Individuals that can contribute sperm for the conception of a child must commit to the
use of study approved methods of contraception during the trial period and for 6
months after the last dose of obinutuzumab. Such individuals must also refrain from
donation of sperm during study treatment and for 6 months after the last dose of
obinutuzumab
- Individuals of reproductive and lactating potential must agree to stop breastfeeding
and refrain from donation of ova from the start of study treatment (cycle [C]1 day
[D]1) and for 6 months after the last dose of obinutuzumab
Exclusion Criteria:
- Previous or concurrent diagnosis of any other hematologic malignancy
- Any previous CLL-directed treatment. Prior corticosteroids (or ongoing prednisone =<
20 mg daily, or equivalent) for symptom control are permitted. Enrollment will be
considered for those individuals that can taper ongoing use of a corticosteroid at >
20 mg daily to 0 mg within 14 days of C1D1
- Known history of hypersensitivity to
- Humanized or murine monoclonal antibodies or products
- A CD19 or CD20 antibody
- Tafasitamab
- Acalabrutinib
- Receipt of live vaccine within 14 days of trial enrollment
- Prior history of any solid malignancy, unless disease-free for over 2 years, exclusive
of any prior history of squamous cell carcinoma of the skin or cervix, basal cell
carcinoma of the skin, transitional cell urothelial carcinoma, prostate cancer, or
early-stage melanoma. Exceptions will be considered, at the discretion of the
investigator, if the prior treatment (i.e., within 2 years) is not expected to
confound the results of this study
- Patients with history of confirmed progressive multifocal leukoencephalopathy (PML)
- Active autoimmune disease requiring treatment with > 20 mg of prednisone (or
prednisone equivalent daily), apart from autoimmune hemolytic anemia or immune
thrombocytopenic purpura (ITP).
- Evidence of ongoing systemic bacterial, fungal, or viral infection, except localized
fungal infections of skin or nails. NOTE: Participants may be receiving prophylactic
antiviral or antibacterial therapies at the discretion of the investigator
- Seropositivity for, or history of active viral infection with, human immunodeficiency
virus (HIV)
- Known histological transformation from CLL to an aggressive lymphoma (i.e., Richter's
transformation)
- Known bleeding disorders
- Use of warfarin, marcumar, or phenprocoumon unless drug can be discontinued with
normalization of international normalized ratio (INR) (e.g., INR < 2, or baseline)
within 7 days of C1D1
- Any participant having received agents known to be strong and moderate cytochrome P450
3A inhibitors or inducers within 7 days prior to screening / baseline may require
special approval and / or a wash-out period before day 1, at the discretion of the
investigator
- Ongoing use of proton pump inhibitors (PPI). PPI must be discontinued 48 hours prior
to C1D1
- Any severe and / or uncontrolled medical conditions or other conditions that could
affect their participation in the study such as:
- Symptomatic, or history of documented congestive heart failure (New York [NY]
Heart Association functional classification III-IV)
- Left ventricular ejection fraction (LVEF) < 50%
- Poorly controlled atrial fibrillation
- A history of ventricular arrhythmias
- Uncontrolled hypertension (HTN): Defined as hypertension despite the use of > 2
anti-HTN agents at optimal doses
- Myocardial infarction within 6 months of enrollment
- Angina not well-controlled by medication
- Poorly controlled or clinically significant atherosclerotic vascular disease
including cerebrovascular accident (CVA), transient ischemic attack (TIA),
angioplasty, cardiac / vascular stenting within 6 months of enrollment
- Any other significant medical illness, abnormality, or condition that would, in the
investigator's judgement, make the participant inappropriate for study participation
or would put the participant at risk
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