Study of Zanubrutinib, Obinutuzumab, and Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL)

Recruiting now · Phase 2

Conditions studied: Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Leukemia (SLL)

In brief

The purpose of this study is to determine the rate of minimum residual disease (MRD) negative response (i.e. the rate of no evidence of disease) of the study drugs, zanubrutinib, obinutuzumab, and venetoclax, given in combination as a treatment for CLL and/or SLL.

Key facts

Study ID: NCT03824483
Run by: Memorial Sloan Kettering Cancer Center
People needed: 230
Starts: 2019-02-22
Expected to finish: 2027-02-01
Last updated by the study team: 2026-05-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Signed, informed consent
Ability and willingness to comply with the requirements of the study protocol
Age ≥18 years
Diagnosis of the following histories according to the WHO criteria
CLL or SLL
MCL
For patients with SLL, peripheral blood flow cytometry must be positive with CLL-like cells accounting for at least 1% of circulating WBC.
No prior systemic therapy for disease under study except:
prior local radiation for symptomatic disease is permitted
Short course systemic corticosteroids is permissible for disease control, improvement of performance status or non-cancer indication (must be ≤ 14 days and < 100 mg/day prednisone or ≤ 20 mg/day dexamethasone). Steroids must be discontinued prior to study treatment. Inhaled steroids for asthma, topical steroids, and replacement/Stress corticosteroids are permitted. Low-dose steroids for ITP are also permitted up to the equivalent prednisone 20mg/daily at time of eligibility review.
ECOG performance status of 0 to 2
Adequate hematologic parameters unless due to disease under study:
Absolute neutrophil count (ANC) ≥1.0 x 109/L unless neutropenia is clearly due to disease under study (per investigator discretion)
Platelet count ≥ 75,000/mm3 - OR - Platelet count ≥ 20,000/mm3 if thrombocytopenia is clearly due to disease under study (per investigator discretion)
Hemoglobin ≥9.0 g/dL unless anemia is clearly due to marrow involvement due to disease under study (per investigator discretion)
Adequate renal and hepatic function, per laboratory reference range at Screening as follows:
a. AST/SGOT, ALT/SGPT ≤2.0 x ULN b. Total bilirubin ≤ 2.0 x ULN unless:
i. Considered secondary to Gilbert"s syndrome, in which case ≤3 x ULN ii. Considered due to disease under study (Per PI or Co-PI discretion)
c. Creatinine clearance of eGFR>30 mL/min according to the Cockcroft-Gault Equation
For females of childbearing potential, a negative serum pregnancy test within 7 days of study treatment
For female patients of childbearing potential, agreement to use highly effective form(s) of contraception (i.e., one that results in a low failure rate [<1% per year] when used consistently and correctly) or remain abstinent (refrain from heterosexual intercourse) during the treatment period and to continue its use for 90 days after the last dose of zanubrutinib AND 30 days after the last dose of venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)
A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>/= 12 continuous months of amenorrhea with no identified cause other than menopause), and it not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Mullerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.
Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
For men with a female partner of childbearing potential or a pregnant female partnet: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom during the treatment period and to continue its use for 90 days after the last dose of zanubrutinib AND, 30 days after the last dose of venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)

You may not qualify if…

Other malignancies:
Known active histological transformation from CLL to an aggressive lymphoma (i.e., Richter"s transformation)
Active malignancy or systemic therapy for another malignancy within 3 years; local/regional therapy with curative intent such as surgical resection or localized radiation within 3 years of treatment is permitted
Other diagnosis of active cancer
Co-morbidities:
Any uncontrolled illness that in the opinion of the investigator would preclude administration of study therapy (e.g. significant active infections, hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction)
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 requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1
Known bleeding diathesis
Prior major surgical procedure within 4 weeks of study, or anticipation of need for a major surgical procedure during the course of the study
Known CNS hemorrhage or stroke within 6 months of the study
History of progressive multifocal leukoencephalopathy (PML)
History of HIV infection
Patients with a history of HIV infection that is well controlled on antiretroviral therapy are eligible if all of the following criteria are met: (1) undetectable HIV viral load by standard clinical assay AND (2) CD4+ T cell count of ≥ 200 cells/microliter
NOTE: Many HIV regimens are excluded based on drug interactions, and concomitant antiretroviral therapy need to cleared by the clinical pharmacist and approved by the site PI)
Active hepatitis B (chronic or acute) or hepatitis C infection a. Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody [HBcAb] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to take appropriate anti-viral prophylaxis as indicated and undergo monthly DNA testing.
b. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
Congestive heart failure, New York Heart Association classification III/IV
Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment
Known condition or other clinical situation that would affect oral absorption
Psychiatric illness/social situations that would interfere with study compliance
Inability to swallow a large number of tablets
Concomitant medications and drug interactions:
Administration within 7 days prior to the first dose of study drug or concurrent therapy with strong inhibitors or inducers of CYP3A, CYP2C8, CYP2C9 and CYP2C19. The same applied for moderate inhibitors or inducers of CY_3A
Live-virus vaccines given within 28 days prior to the initiation of study treatment

Where it is running

Northwestern University — Evanston, Illinois, United States (enrolling)
Massachusetts General Hospital (Data Collection and Specimen Analysis) — Boston, Massachusetts, United States (enrolling)
Memorial Sloan Kettering at Basking Ridge — Basking Ridge, New Jersey, United States (enrolling)
Memorial Sloan Kettering Monmouth — Middletown, New Jersey, United States (enrolling)
Memorial Sloan Kettering Commack — Commack, New York, United States (enrolling)
Memorial Sloan Kettering Westchester — Harrison, New York, United States (enrolling)
Memorial Sloan Kettering Cancer Center — New York, New York, United States (enrolling)
Memorial Sloan Kettering Nassau — Uniondale, New York, United States (enrolling)

Full record on ClinicalTrials.gov

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