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OncoMatch/Clinical Trials/NCT03824483

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

Is NCT03824483 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including Zanubrutinib and Obinutuzumab for chronic lymphocytic leukemia (cll).

Phase 2RecruitingMemorial Sloan Kettering Cancer CenterNCT03824483Data as of May 2026

Treatment: Zanubrutinib · Obinutuzumab · VenetoclaxThe 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.

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Extracted eligibility criteria

Cancer type

Chronic Lymphocytic Leukemia

Acute Lymphoblastic Leukemia

Biomarker criteria

Required: TP53 mutation

Required: TP53 overexpression (strong nuclear staining of >30% positive nuclei)

Disease stage

Required: Stage II, III, IV

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

No prior treatment (treatment-naive required)
Max 0 prior lines

Cannot have received: systemic therapy

Exception: 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); inhaled/topical/replacement/stress corticosteroids and low-dose steroids for ITP up to prednisone 20mg/daily at eligibility review are permitted

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.

Cannot have received: anti-CD20 monoclonal antibody

Exception: for non-malignant indication

Prior anti-CD20 monoclonal antibody therapy for non-malignant indication

Cannot have received: systemic therapy

Exception: prior single site of local radiation for symptomatic disease is permitted

No prior systemic therapy for CLL; prior single site of local radiation for symptomatic disease is permitted

Cannot have received: obinutuzumab (obinutuzumab)

Exception: known hypersensitivity (IgE-mediated) reaction to obinutuzumab or to any of its excipients

Obinutuzumab is contraindicated in patients with a known hypersensitivity (IgE-mediated) reaction to obinutuzumab or to any of its excipients

Lab requirements

Blood counts

ANC ≥1.0 x 10^9/L unless neutropenia is clearly due to disease under study; Platelet count ≥ 75,000/mm3 OR ≥ 20,000/mm3 if thrombocytopenia is clearly due to disease under study; Hemoglobin ≥9.0 g/dL unless anemia is clearly due to marrow involvement due to disease under study

Kidney function

Creatinine clearance of eGFR>30 mL/min according to the Cockcroft-Gault Equation

Liver function

AST/SGOT, ALT/SGPT ≤2.0 x ULN; Total bilirubin ≤ 2.0 x ULN unless secondary to Gilbert's syndrome (≤3 x ULN) or due to disease under study (per PI or Co-PI discretion)

Adequate hematologic parameters unless due to disease under study: ANC ≥1.0 x 10^9/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

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Northwestern University · Evanston, Illinois
  • Massachusetts General Hospital (Data Collection and Specimen Analysis) · Boston, Massachusetts
  • Memorial Sloan Kettering at Basking Ridge · Basking Ridge, New Jersey
  • Memorial Sloan Kettering Monmouth · Middletown, New Jersey
  • Memorial Sloan Kettering Commack · Commack, New York

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