RECRUITING

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

Conditions

Chronic Lymphocytic Leukemia (CLL)Small Lymphocytic Leukemia (SLL)Zanubrutinib Obinutuzumab Venetoclax 18-427

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Phase 2 Study of Zanubrutinib, Obinutuzumab, and Venetoclax in Previously Untreated Patients with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) and Mantle Cell Lymphoma (MCL)

Quick Facts

Study Start:2019-02-22

Study Completion:2025-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03824483

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 1. CLL or SLL 2. 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: 1. prior local radiation for symptomatic disease is permitted 2. 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: 1. Absolute neutrophil count (ANC) ≥1.0 x 109/L unless neutropenia is clearly due to disease under study (per investigator discretion) 2. Platelet count ≥ 75,000/mm3 - OR - Platelet count ≥ 20,000/mm3 if thrombocytopenia is clearly due to disease under study (per investigator discretion) 3. 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: * 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) 1. 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, or venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later) 1. Diagnosis of untreated CLL or SLL according to WHO criteria 2. For patients with SLL, peripheral blood flow cytometry must be positive with CLL-like cells accounting for at least 1% of circulating WBC 3. No prior systemic therapy for CLL: prior single site of local radiation for symptomatic disease is permitted 4. Subject requires treatment according to IWCLL guidelines (See Appendix A) 1. Diagnosis of untreated stage II-IV mantle cell lymphoma 1. Diagnosis of untreated stage II-IV mantle cell lymphoma 1. Prior radiotherapy for localized disease is permitted 2. Patients must meet one of the following criteria (a or b):	* 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 * 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 1. 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 * 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. * 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 * Live-virus vaccines given within 28 days prior to the initiation of study treatment * Immunotherapy * Hormone therapy (other than contraceptives, hormone replacement therapy, or megestrol acetate) * Any therapies intended for the treatment of lymphoma/leukemia whether FDA approved or experimental (outside of this study) * Radiation therapy intended to treat MCL or CLL/SLL * Warfarin or warfarin derivatives * Consumption of one or more of the following within 3 days prior to the first dose of study drug: * Prior anti-CD20 monoclonal antibody therapy for non-malignant indication * Obinutuzumab is contraindicated in patients with a known hypersensitivity (IgE-mediated) reaction to obinutuzumab or to any of its excipients * Prior systemic therapy for CLL; prior single site of local radiation for symptomatic disease is permitted * Females who are currently pregnant or breastfeeding * Participation in a separate investigational therapeutic study unless authorized by the investigator

Inclusion Criteria

Exclusion Criteria

* 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
1. CLL or SLL
2. 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:
1. prior local radiation for symptomatic disease is permitted
2. 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:
1. Absolute neutrophil count (ANC) ≥1.0 x 109/L unless neutropenia is clearly due to disease under study (per investigator discretion)
2. Platelet count ≥ 75,000/mm3 - OR - Platelet count ≥ 20,000/mm3 if thrombocytopenia is clearly due to disease under study (per investigator discretion)
3. 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:
* 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)
1. 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, or venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)
1. Diagnosis of untreated CLL or SLL according to WHO criteria 2. For patients with SLL, peripheral blood flow cytometry must be positive with CLL-like cells accounting for at least 1% of circulating WBC 3. No prior systemic therapy for CLL: prior single site of local radiation for symptomatic disease is permitted 4. Subject requires treatment according to IWCLL guidelines (See Appendix A)
1. Diagnosis of untreated stage II-IV mantle cell lymphoma
1. Diagnosis of untreated stage II-IV mantle cell lymphoma
1. Prior radiotherapy for localized disease is permitted
2. Patients must meet one of the following criteria (a or b):

* 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
* 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
1. 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
* 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.
* 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
* Live-virus vaccines given within 28 days prior to the initiation of study treatment
* Immunotherapy
* Hormone therapy (other than contraceptives, hormone replacement therapy, or megestrol acetate)
* Any therapies intended for the treatment of lymphoma/leukemia whether FDA approved or experimental (outside of this study)
* Radiation therapy intended to treat MCL or CLL/SLL
* Warfarin or warfarin derivatives
* Consumption of one or more of the following within 3 days prior to the first dose of study drug:
* Prior anti-CD20 monoclonal antibody therapy for non-malignant indication
* Obinutuzumab is contraindicated in patients with a known hypersensitivity (IgE-mediated) reaction to obinutuzumab or to any of its excipients
* Prior systemic therapy for CLL; prior single site of local radiation for symptomatic disease is permitted
* Females who are currently pregnant or breastfeeding
* Participation in a separate investigational therapeutic study unless authorized by the investigator

Contacts and Locations

Study Contact

Andrew Zelenetz, MD, PhD

CONTACT

212-639-2656

zeleneta@mskcc.org

Anthony Mato, MD

CONTACT

212-639-8596

Principal Investigator

Andrew Zelenetz, MD, PhD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Northwestern University

Evanston, Illinois, 60208

United States

Massachusetts General Hospital (Data Collection and Specimen Analysis)

Boston, Massachusetts, 02114

United States

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Commack

Commack, New York, 11725

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553

United States

Memorial Sloan Kettering Westchester

West Harrison, New York, 10604

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Andrew Zelenetz, MD, PhD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-02-22

Study Completion Date2025-02

Study Record Updates

Study Start Date2019-02-22

Study Completion Date2025-02

Terms related to this study

Keywords Provided by Researchers

Zanubrutinib
Obinutuzumab
Venetoclax
18-427

Additional Relevant MeSH Terms

Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Leukemia (SLL)