Tacabrutideg and Sonrotoclax, With Response-Guided Obinutuzumab, for the Treatment of Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Phase 2 Study of Time-Limited BGB-16673 and Sonrotoclax With MRD-Guided Addition of Obinutuzumab for Treatment-Naïve Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Procedures mentioned: Blood draws, CT scans
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "Patients also undergo transthoracic echocardiography (TTE) or multigated acquisition scan (MUGA) at screening and undergo computed tomography (CT) and collection of blood samples throughout the trial."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This phase 2 study tests tacabrutideg and sonrotoclax together for adults with untreated CLL or SLL, two types of blood cancer. Obinutuzumab may be added if the cancer does not fully respond to the first two drugs.
This phase II trial tests how well tacabrutideg and sonrotoclax, with response-guided addition of obinutuzumab, works in treating patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Tacabrutideg is a drug that degrades a protein called Bruton's tyrosine kinase (BTK). By degrading BTK, tacabrutideg inhibits the activation of signaling pathways that help cancer cells survive, inhibiting the growth of cancer cells that express the BTK protein. Sonrotoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving tacabrutideg together with sonrotoclax may kill more cancer cells than giving either drug alone, and giving obinutuzumab after initial treatment with tacabrutideg and sonrotoclax may improve disease response in patients whose CLL or SLL didn't respond completely to initial treatment.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be age 18 or older, able to give written consent, and able to follow study rules.
- Have confirmed CLL or SLL that needs treatment under standard guidelines.
- Have cancer that can be measured through scans, blood tests, or bone marrow tests.
- Have had no treatment aimed at CLL. Past treatment for certain immune-related blood problems is allowed if it ended at least 6 months ago.
- Be able to care for yourself and be out of bed or a chair for at least half of your waking hours.
- Meet blood count requirements. Some exceptions and support treatments are allowed when cancer affects the bone marrow.
- Meet kidney function requirements based on blood tests or tests of how well the kidneys filter blood.
- Follow birth control and egg or sperm donation rules during and after treatment, if able to have children. Those able to become pregnant must have a negative pregnancy test within 7 days before treatment.
Who can't join
- Have Richter transformation, when CLL or SLL changes into a faster-growing cancer, or disease in the brain or spinal cord.
- Have an active infection needing medicine by injection or IV, or active hepatitis B or C. Some people with treated or controlled hepatitis may join with required monitoring and treatment.
- Have HIV with a detectable virus level or a CD4 immune cell count of 350 or less, or an AIDS-related infection in the past year. Controlled HIV may be allowed with stable treatment.
- Have a history of another cancer, unless it meets the study’s exceptions, such as no signs of cancer for at least 2 years after treatment.
- Have had a stroke from a blocked blood vessel or bleeding inside the skull within 6 months, or major surgery within 28 days before treatment. You must also have recovered from surgery.
- Have certain serious heart problems, a heart attack within 3 months, or uncontrolled high blood pressure.
- Have taken steroids to fight cancer within 7 days before treatment. Steroids for symptoms and a short course of up to 7 days to control CLL or SLL may be allowed.
- Be unable to follow study requirements.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: * Age \>= 18 at time of study enrollment who are capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol * Confirmed diagnosis of CLL/SLL by 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria * Meets criteria for treatment for iwCLL criteria * Measurable disease, as defined by at least one of the following: * At least one lymph node \> 1.5 cm in longest diameter, as measurable by computed tomography (CT) or magnetic resonance imaging (MRI) * Clonal lymphocytes \>= 5 x 10\^9/L present on peripheral blood cytometry * Bone marrow involvement of at least 30% by flow cytometry with peripheral blood cytopenias * Has not received any other CLL-directed therapy (e.g., must be TN). Patients who have received treatment for the treatment of immune thrombocytopenia or autoimmune hemolytic anemia (e.g. with rituximab or steroids) will be eligible if last treatment was \>= 6 months prior to enrollment * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Absolute neutrophil count (ANC) \>= 0.75 x 10\^9/L if bone marrow involvement; otherwise, \>= 1.00 x 10\^9/L * Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed. Patients must be free from growth factor support as evidenced by an ANC dated \>= 14 days following the most recent administration of peg-filgrastim (or other pegylated myeloid growth factors) and \>= 4 days following the most recent administration of filgrastim or other myeloid growth factors * Hemoglobin \>= 8.0 g/dL, unless secondary to bone marrow infiltration by the underlying malignancy * Hemoglobin \>= 80 g/L (independent of growth factor support or transfusion, defined as no growth factor support for \>= 7 days and/or transfusion for \>= 3 days); patients may have hemoglobin \< 80 g/L with or without growth factor or transfusion as above if the reduced hemoglobin is secondary to bone marrow infiltration by the underlying malignancy * Platelets \>= 50,000/uL * Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed * Creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 30 mL/min for participants with creatinine levels \> 1.5 x institutional ULN * Creatinine clearance (CrCl) should be calculated per institutional standard * Women of childbearing potential (WOCBP) must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and following the last dose of the drug, whichever comes last. (Note: when oral hormonal contraceptives are selected, an additional barrier method is required) All WOCBP must have a negative pregnancy test =\< 7 days prior to the first dose of the study drug: * Duration of highly effective method of birth control following last dose of drug, whichever comes last: * BGB-16673: \>= 30 days * Sonrotoclax: \>= 7 days * Obinutuzumab: 18 months * WOCBP defined as a participant who is assigned female sex at birth and is postmenarcheal, has not reached a postmenopausal state (\>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus) * Nonsterile men must also use a highly effective method of birth control along with barrier contraception and refrain from donating sperm for the duration of the study treatment period and then for the following duration: * Duration of highly effective method of birth control following last dose of drug, whichever comes last: * BGB-16673: \>= 30 days * Sonrotoclax: \>= 7 days * Obinutuzumab: 6 months * A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Men with known "low sperm counts" (consistent with "subfertility") are not to be considered sterile for purposes of this study Exclusion Criteria: * Diagnosis of Richter transformation * Central nervous system disease at time of study enrollment * Active fungal, bacterial, and/or viral infection requiring parenteral systemic therapy * Positive serological status reflecting active hepatitis B: * Presence of hepatitis B virus surface antigen (HBsAg) * Patients with presence of hepatitis B virus core antibody (HBcAb), in the absence of HBsAg, with detectable hepatitis B virus (HBV) deoxyribonucleic acid (DNA) * Note: * Patients with presence of HBcAb but undetectable HBV DNA and who are willing to undergo HBV DNA monitoring every 4 weeks for HBV reactivation are eligible * Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention * Positive serological status reflecting active hepatitis C: * Patients with the presence of hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid (RNA) * Note: * Participants must have completed curative anti-viral therapy for HCV at least 4 weeks prior to study enrollment and are willing to undergo HCV RNA monitoring every 4 weeks for HCV reactivation are eligible * HIV with a detectable viral load or a CD4 count =\< 350 cells/uL at time of screening * Participants with HIV who do not meet the above criteria are eligible if they are on a stable antiretroviral therapy (ART) regimen (ART must not be strong CYP3A4 inducers) for at least 4 weeks prior to study entry and are compliant with ART are eligible * Participants with an AIDS-defining opportunistic infection in the past 12 months prior to screening are not eligible * History of a second malignancy, except for the conditions listed below: * Potentially curative treatment has been completed with no evidence of disease for \>= 2 years * The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder * Localized prostate cancer with Gleason score =\< 6 * Patients who are unable to comply with the requirements of the protocol * History of ischemic stroke or intracranial hemorrhage within 6 months before first dose of study drug * Patients with any major surgical procedure =\< 28 days before the first dose of study drug. Patients must have recovered adequately from the procedure and/or complications from the procedure before the first dose of study drug * Patients with clinically significant cardiovascular disease such as the following: * Myocardial infarction within 3 months of the first dose of study drug * New York Heart Association classification III or IV congestive heart failure * History of clinically significant arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) * Fridericia's formula-corrected QT interval (QTcF) \> 480 milliseconds based on Fridericia's formula. Patients with prolonged QTcF due to bundle branch block can be allowed after consultation with the cardiologists. * History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place * Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure \>= 160 mmHg and diastolic blood pressure \>= 100 mmHg at screening * Patients who have received corticosteroids given with antineoplastic intent (symptom control will not be considered as antineoplastic intent) =\< 7 days before the first dose of study drug. Note: A short course (=\< 7 days) of systemic steroid use is allowed if needed to control CLL/SLL-related symptoms and it is tapered off within 5 days after initiation of study drug. Ongoing systemic corticosteroid treatment (defined as \>= 10 mg/day of prednisone or equivalent) is not allowed unless willing to receive anti-fungal prophylaxis during the entire treatment period * Requires treatment with warfarin or other vitamin K antagonists * History of known bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention * Patients who have a history of severe allergic reactions or hypersensitivity to the active ingredients of the study drug(s) * Female patients who are pregnant or are breastfeeding * Patients who are unable to swallow tablets or with disease/procedure significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastrointestinal perforation or fistulae. Note: Gastroesophageal reflux disease under treatment with proton-pump inhibitors is allowed (assuming no drug interaction potential) * Patients with known contraindications to azole antifungal agents, including hypersensitivity reactions
Study sites (1)
WA
- Fred Hutch/University of Washington Cancer Consortium · Seattle, WA 98109Jennifer J. Huang, MD, PhD · Study contact · 206-667-1358 · jhuang3@fredhutch.orgJennifer J. Huang, MD, PhD · Principal investigatorMore trials in Seattle