Acalabrutinib With or Without Obinutuzumab in Treating Patients With Early-Stage Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
NCT ID: NCT03516617
Last Updated: 2025-09-05
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
RECRUITING
Clinical Phase
PHASE2
Total Enrollment
120 participants
Study Classification
INTERVENTIONAL
Study Start Date
2018-09-10
Study Completion Date
2030-10-16
Brief Summary
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This phase II trials studies how well acalabrutinib with or without obinutuzumab works in treating patients with early-stage chronic lymphocytic leukemia or small lymphocytic lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving acalabrutinib with or without obinutuzumab will work better in treating patients with early-stage chronic lymphocytic leukemia or small lymphocytic lymphoma.
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Detailed Description
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PRIMARY OBJECTIVES:
I. To compare the bone marrow minimal residual disease (MRD)-negative complete response (CR) rate of acalabrutinib alone and acalabrutinib/obinutuzumab in early stage asymptomatic chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients who are high and very high risk by CLL-International Prognostic Index (IPI). (Arms A and B) II. To evaluate time to first therapy (TFT) in early stage asymptomatic CLL/SLL patients with low and intermediate-risk by CLL-IPI. (Arm C)
SECONDARY OBJECTIVES:
I. To compare the safety of acalabrutinib alone and acalabrutinib/obinutuzumab in early stage asymptomatic CLL/SLL patients who are high and very high risk by CLL-IPI.
II. To compare the overall response rate (ORR), progression-free survival (PFS), time to next therapy (TNT) and overall survival (OS) of acalabrutinib alone and acalabrutinib/obinutuzumab in early stage asymptomatic CLL/SLL patients who are at high and very high risk by CLL-IPI.
III. To determine the progression-free survival (PFS) and overall survival (OS) in early stage asymptomatic CLL/SLL patients with low and intermediate risk by CLL-IPI.
EXPLORATORY OBJECTIVE:
I. To evaluate the quality of life using Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QOL) survey.
CORRELATIVE RESEARCH:
I. To compare the peripheral blood immune profile using 8-color flow cytometry, to assess changes in T-cells, natural killer (NK)-cells, and NK-T cells at baseline and during active treatment among patients receiving either acalabrutinib alone or acalabrutinib and obinutuzumab.
II. To determine changes in the peripheral blood immune profile using 8-color flow cytometry to assess changes in T-cells, NK-cells, and NK-T cells at baseline and during event monitoring in patients with low and intermediate risk by CLL-IPI.
III. Signal pathway studies-BTK, ERK, PLC gamma and S6 protein levels and phosphorylation status will be assessed by Western blot methodology using specific antibodies to pull down specific proteins from cell lysates.
IV. To confirm if in vitro cell killing is via apoptosis we will also assess PARP and caspase 3 cleavage.
V. Apoptotic protein studies-MCL-1, XIAP levels will be determined by Western blot methodology using specific antibodies to pull down these specific proteins from cell lysates.
VI. Bone marrow aspirates will be studied for hematopoietic function in two ways:
VIa. Estimation of colony forming capacity by purified hematopoietic stem cells (HSCs).
VIb. Evaluation of the levels of HSCs and their differentiated progeny (i.e. MPP, CMP, CLP).
VII. Paired bone marrow and blood samples will be evaluated for the levels of innate effector cells.
VIII. Perform targeted sequencing of 59 genes mainly grouped in 8 biological pathways: NOTCH1, B-cell signaling, deoxyribonucleic acid (DNA) damage response, chromatin modifiers, ribonucleic acid (RNA) metabolism, NF-kappaB pathway, cell cycle and apoptosis.
IX. Screen 2 genes previously associated with resistance to BTK inhibitors (BTK and PLCG2).
OUTLINE: Patients with high or very high risk CLL-IPI are randomized to Arm A or Arm B. Patients with intermediate or low risk are assigned to Arm C.
ARM A: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive acalabrutinib PO BID on days 1-84. Treatment repeats every 84 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment with acalabrutinib If MRD negative CR/CR with incomplete marrow recovery (CRi) is not achieved after 12 cycles.
ARM B: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28 and obinutuzumab intravenously (IV) on days 1, 2, 8, and 15 of cycle 1 and days 1 of subsequent cycles. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive acalabrutinib PO BID on days 1-84. Treatment repeats every 84 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment with acalabrutinib If MRD negative CR/CRi is not achieved after 12 cycles.
ARM C: Patients will be observed every 6 months for up to 2 years.
After completion of study treatment, patients are followed up every 6 months for up to 10 years.
I. To compare the bone marrow minimal residual disease (MRD)-negative complete response (CR) rate of acalabrutinib alone and acalabrutinib/obinutuzumab in early stage asymptomatic chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients who are high and very high risk by CLL-International Prognostic Index (IPI). (Arms A and B) II. To evaluate time to first therapy (TFT) in early stage asymptomatic CLL/SLL patients with low and intermediate-risk by CLL-IPI. (Arm C)
SECONDARY OBJECTIVES:
I. To compare the safety of acalabrutinib alone and acalabrutinib/obinutuzumab in early stage asymptomatic CLL/SLL patients who are high and very high risk by CLL-IPI.
II. To compare the overall response rate (ORR), progression-free survival (PFS), time to next therapy (TNT) and overall survival (OS) of acalabrutinib alone and acalabrutinib/obinutuzumab in early stage asymptomatic CLL/SLL patients who are at high and very high risk by CLL-IPI.
III. To determine the progression-free survival (PFS) and overall survival (OS) in early stage asymptomatic CLL/SLL patients with low and intermediate risk by CLL-IPI.
EXPLORATORY OBJECTIVE:
I. To evaluate the quality of life using Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QOL) survey.
CORRELATIVE RESEARCH:
I. To compare the peripheral blood immune profile using 8-color flow cytometry, to assess changes in T-cells, natural killer (NK)-cells, and NK-T cells at baseline and during active treatment among patients receiving either acalabrutinib alone or acalabrutinib and obinutuzumab.
II. To determine changes in the peripheral blood immune profile using 8-color flow cytometry to assess changes in T-cells, NK-cells, and NK-T cells at baseline and during event monitoring in patients with low and intermediate risk by CLL-IPI.
III. Signal pathway studies-BTK, ERK, PLC gamma and S6 protein levels and phosphorylation status will be assessed by Western blot methodology using specific antibodies to pull down specific proteins from cell lysates.
IV. To confirm if in vitro cell killing is via apoptosis we will also assess PARP and caspase 3 cleavage.
V. Apoptotic protein studies-MCL-1, XIAP levels will be determined by Western blot methodology using specific antibodies to pull down these specific proteins from cell lysates.
VI. Bone marrow aspirates will be studied for hematopoietic function in two ways:
VIa. Estimation of colony forming capacity by purified hematopoietic stem cells (HSCs).
VIb. Evaluation of the levels of HSCs and their differentiated progeny (i.e. MPP, CMP, CLP).
VII. Paired bone marrow and blood samples will be evaluated for the levels of innate effector cells.
VIII. Perform targeted sequencing of 59 genes mainly grouped in 8 biological pathways: NOTCH1, B-cell signaling, deoxyribonucleic acid (DNA) damage response, chromatin modifiers, ribonucleic acid (RNA) metabolism, NF-kappaB pathway, cell cycle and apoptosis.
IX. Screen 2 genes previously associated with resistance to BTK inhibitors (BTK and PLCG2).
OUTLINE: Patients with high or very high risk CLL-IPI are randomized to Arm A or Arm B. Patients with intermediate or low risk are assigned to Arm C.
ARM A: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive acalabrutinib PO BID on days 1-84. Treatment repeats every 84 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment with acalabrutinib If MRD negative CR/CR with incomplete marrow recovery (CRi) is not achieved after 12 cycles.
ARM B: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28 and obinutuzumab intravenously (IV) on days 1, 2, 8, and 15 of cycle 1 and days 1 of subsequent cycles. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive acalabrutinib PO BID on days 1-84. Treatment repeats every 84 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment with acalabrutinib If MRD negative CR/CRi is not achieved after 12 cycles.
ARM C: Patients will be observed every 6 months for up to 2 years.
After completion of study treatment, patients are followed up every 6 months for up to 10 years.
Conditions
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Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Arm A (acalabrutinib)
Patients receive acalabrutinib PO BID on days 1-28. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive acalabrutinib PO BID on days 1-84. Treatment repeats every 84 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment with acalabrutinib If MRD negative CR/CRi is not achieved after 12 cycles.
Group Type
EXPERIMENTAL
Acalabrutinib
Intervention Type
DRUG
Given PO
Laboratory Biomarker Analysis
Intervention Type
OTHER
Correlative studies
Quality-of-Life Assessment
Intervention Type
OTHER
Ancillary studies
Arm B (acalabrutinib, obinutuzumab)
Patients receive acalabrutinib PO BID on days 1-28 and obinutuzumab IV on days 1, 2, 8, and 15 of cycle 1 and days 1 of subsequent cycles. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive acalabrutinib PO BID on days 1-84. Treatment repeats every 84 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment with acalabrutinib If MRD negative CR/CRi is not achieved after 12 cycles.
Group Type
EXPERIMENTAL
Acalabrutinib
Intervention Type
DRUG
Given PO
Laboratory Biomarker Analysis
Intervention Type
OTHER
Correlative studies
Obinutuzumab
Intervention Type
BIOLOGICAL
Given IV
Quality-of-Life Assessment
Intervention Type
OTHER
Ancillary studies
Arm C (observation)
Patients will be observed every 6 months for up to 2 years.
Group Type
ACTIVE_COMPARATOR
Laboratory Biomarker Analysis
Intervention Type
OTHER
Correlative studies
Patient Observation
Intervention Type
OTHER
Undergo observation
Quality-of-Life Assessment
Intervention Type
OTHER
Ancillary studies
Interventions
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Acalabrutinib
Given PO
Intervention Type
DRUG
Laboratory Biomarker Analysis
Correlative studies
Intervention Type
OTHER
Obinutuzumab
Given IV
Intervention Type
BIOLOGICAL
Patient Observation
Undergo observation
Intervention Type
OTHER
Quality-of-Life Assessment
Ancillary studies
Intervention Type
OTHER
Other Intervention Names
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ACP-196
Bruton Tyrosine Kinase Inhibitor ACP-196
Anti-CD20 Monoclonal Antibody R7159
GA-101
GA101
Gazyva
huMAB(CD20)
R7159
RO 5072759
RO-5072759
RO5072759
Active Surveillance
deferred therapy
expectant management
Observation
Watchful Waiting
Quality of Life Assessment
Eligibility Criteria
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Inclusion Criteria
* Age \>= 18 years
* Diagnosis of:
* Biopsy-proven small lymphocytic lymphoma (SLL) , or
* Diagnosis of chronic lymphocytic leukemia (CLL) with a clonal B-cell population in the peripheral blood with immunophenotyping consistent with CLL as follows:
* The population of lymphocytes share both B-cell antigens (CD19, CD20 \[typically dim expression\], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)
* Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. IGHV analysis)
* Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t(11;14)(IgH/CCND1)
* Patients must be previously untreated
* Note: Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL or SLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments or supplemental vitamins) will not be considered "prior treatment"; prior corticosteroid therapy for an indication other than CLL/SLL will not be considered "prior treatment"
* All patients will undergo testing for prognostic factors according to the CLL-IPI (testing obtained =\< 730 days prior to registration)
* Note: If the results for any of the prognostic factors included in the CLL-IPI are unknown including IGVH mutation status results not being available due to a failed laboratory assay, the patient is not eligible
* Note: When determining CLL-IPI, use most recent test results, if more than one result is available
* Note: Patients with CLL-IPI risk category of high risk or very high risk (total score of 4-10) will be randomized to Arms A or B
* Note: Patients with CLL-IPI risk category of low risk or intermediate risk (total score of 0-3) will be registered to Arm C
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
* Provide written informed consent
* Willing to provide blood and saliva samples for correlative research purposes
* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Platelet count \>= 100,000/mm\^3 (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Hemoglobin \>= 11.0 g/dL (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Aspartate aminotransferase (aspartate transaminase \[AST\]) =\< 3 x upper limit of normal (ULN) (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Creatinine =\< 1.5 X ULN (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Total bilirubin =\< 1.5 x upper limit of normal (ULN) (or total bilirubin =\< 3.0 x ULN with direct bilirubin =\< 1.5 x ULN in patients with well-documented Gilbert's syndrome (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (PTT) =\< 1.5 X ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants (obtained =\< 30 days prior to randomization)
* Negative serum pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only
* Will provide bone marrow aspirate sample for correlative research purposes
* Diagnosis of:
* Biopsy-proven small lymphocytic lymphoma (SLL) , or
* Diagnosis of chronic lymphocytic leukemia (CLL) with a clonal B-cell population in the peripheral blood with immunophenotyping consistent with CLL as follows:
* The population of lymphocytes share both B-cell antigens (CD19, CD20 \[typically dim expression\], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)
* Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. IGHV analysis)
* Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t(11;14)(IgH/CCND1)
* Patients must be previously untreated
* Note: Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL or SLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments or supplemental vitamins) will not be considered "prior treatment"; prior corticosteroid therapy for an indication other than CLL/SLL will not be considered "prior treatment"
* All patients will undergo testing for prognostic factors according to the CLL-IPI (testing obtained =\< 730 days prior to registration)
* Note: If the results for any of the prognostic factors included in the CLL-IPI are unknown including IGVH mutation status results not being available due to a failed laboratory assay, the patient is not eligible
* Note: When determining CLL-IPI, use most recent test results, if more than one result is available
* Note: Patients with CLL-IPI risk category of high risk or very high risk (total score of 4-10) will be randomized to Arms A or B
* Note: Patients with CLL-IPI risk category of low risk or intermediate risk (total score of 0-3) will be registered to Arm C
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
* Provide written informed consent
* Willing to provide blood and saliva samples for correlative research purposes
* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Platelet count \>= 100,000/mm\^3 (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Hemoglobin \>= 11.0 g/dL (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Aspartate aminotransferase (aspartate transaminase \[AST\]) =\< 3 x upper limit of normal (ULN) (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Creatinine =\< 1.5 X ULN (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Total bilirubin =\< 1.5 x upper limit of normal (ULN) (or total bilirubin =\< 3.0 x ULN with direct bilirubin =\< 1.5 x ULN in patients with well-documented Gilbert's syndrome (obtained =\< 30 days prior to randomization)
* For high risk and very high risk CLL-IPI (Arms A and B) only: Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (PTT) =\< 1.5 X ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants (obtained =\< 30 days prior to randomization)
* Negative serum pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only
* Will provide bone marrow aspirate sample for correlative research purposes
Exclusion Criteria
* Date of CLL/SLL diagnosis \>= 24 months prior to registration
* Prior exposure to ibrutinib or to a BCR inhibitor (e.g. Btk or PI3 kinase or Syk inhibitors) or a BCL-2 inhibitor (e.g. venetoclax)
* Known central nervous system (CNS) lymphoma or leukemia
* Patients with any of the following indications for chemotherapy:
* Evidence of progressive marrow failure as manifested by the development of or worsening anemia (=\< 11 g/dL) and/or thrombocytopenia (=\< 100 x 10\^9/L) not due to autoimmune disease
* Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly
* One or more of the following disease-related symptoms:
* Weight loss \>= 10% within the previous 6 months
* Extreme fatigue attributed to CLL
* Fevers \>= 100.4 degrees Fahrenheit (F) for 2 weeks without evidence of infection
* Drenching night sweats without evidence of infection
* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* Patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
* Other active malignancy =\< 2 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer, carcinoma-in-situ of the cervix, or early stage prostate cancer
* History of myocardial infarction =\< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
* For high risk and very high risk CLL-IPI (Arms A and B) only:
* Any of the following:
* Pregnant persons
* Nursing persons
* Persons of childbearing potential who are unwilling to employ highly effective contraception
* Serologic status reflecting active hepatitis B or C infection
* NOTE: Subjects with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result before randomization; those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded
* History of stroke or intracranial hemorrhage within 6 months before randomization
* History of bleeding diathesis (e.g. hemophilia, von Willebrand disease)
* Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon) within 7 days of first dose of study drug and while on study
* Requires treatment with a strong CYP3A inducer
* Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening
* History of confirmed progressive multifocal leukoencephalopathy (PML)
* Received a vaccination with a live vaccine =\< 28 days prior to randomization
* Prior exposure to ibrutinib or to a BCR inhibitor (e.g. Btk or PI3 kinase or Syk inhibitors) or a BCL-2 inhibitor (e.g. venetoclax)
* Known central nervous system (CNS) lymphoma or leukemia
* Patients with any of the following indications for chemotherapy:
* Evidence of progressive marrow failure as manifested by the development of or worsening anemia (=\< 11 g/dL) and/or thrombocytopenia (=\< 100 x 10\^9/L) not due to autoimmune disease
* Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly
* One or more of the following disease-related symptoms:
* Weight loss \>= 10% within the previous 6 months
* Extreme fatigue attributed to CLL
* Fevers \>= 100.4 degrees Fahrenheit (F) for 2 weeks without evidence of infection
* Drenching night sweats without evidence of infection
* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* Patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
* Other active malignancy =\< 2 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer, carcinoma-in-situ of the cervix, or early stage prostate cancer
* History of myocardial infarction =\< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
* For high risk and very high risk CLL-IPI (Arms A and B) only:
* Any of the following:
* Pregnant persons
* Nursing persons
* Persons of childbearing potential who are unwilling to employ highly effective contraception
* Serologic status reflecting active hepatitis B or C infection
* NOTE: Subjects with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result before randomization; those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded
* History of stroke or intracranial hemorrhage within 6 months before randomization
* History of bleeding diathesis (e.g. hemophilia, von Willebrand disease)
* Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon) within 7 days of first dose of study drug and while on study
* Requires treatment with a strong CYP3A inducer
* Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening
* History of confirmed progressive multifocal leukoencephalopathy (PML)
* Received a vaccination with a live vaccine =\< 28 days prior to randomization
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Mayo Clinic
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Sameer A. Parikh, M.D.
Role: PRINCIPAL_INVESTIGATOR
Mayo Clinic in Rochester
Locations
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Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Site Status
RECRUITING
Mayo Clinic in Florida
Jacksonville, Florida, United States
Site Status
RECRUITING
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Site Status
RECRUITING
Countries
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United States
Central Contacts
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Facility Contacts
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Related Links
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https://www.mayo.edu/research/clinical-trials
Mayo Clinic Clinical Trials
Other Identifiers
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NCI-2018-00591
Identifier Type: REGISTRY
Identifier Source: secondary_id
17-008161
Identifier Type: OTHER
Identifier Source: secondary_id
MC168E
Identifier Type: -
Identifier Source: org_study_id
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COMPLETED
PHASE3
Acalabrutinib in Combination With Anti-CD20 and Venetoclax in Relapsed/Refractory or Untreated CLL/SLL/PLL
NCT02296918
COMPLETED
PHASE1
Acalabrutinib, Venetoclax, and Obinutuzumab for Initial Therapy of CLL
NCT03580928
ACTIVE_NOT_RECRUITING
PHASE2
Intermittent Versus Continuous Venetoclax With Acalabrutinib for CLL/SLL
NCT07014917
RECRUITING
PHASE2
Obinutuzumab With High-dose Ibrutinib for the Treatment of Patients With Chronic Lymphocytic Leukemia With Progressive Disease on Single Agent Ibrutinib.
NCT02611908
WITHDRAWN
PHASE1
Acalabrutinib for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
NCT06757647
RECRUITING
PHASE2
Acalabrutinib Safety Study in Untreated and Relapsed or Refractory Chronic Lymphocytic Leukemia Patients
NCT04008706
COMPLETED
PHASE3
Alemtuzumab-Ofatumumab in Previously Untreated Symptomatic Chronic Lymphocytic Leukemia
NCT01361711
ACTIVE_NOT_RECRUITING
PHASE2
Venetoclax-Obinutuzumab +/- Acalabrutinib in R/R CLL
NCT04560322
RECRUITING
PHASE2
Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL
NCT03836261
ACTIVE_NOT_RECRUITING
PHASE3
Study to Assess Change in Disease Activity and Adverse Events of Oral Venetoclax in Combination With Intravenous (IV) Obinutuzumab or Oral Ibrutinib in Adult Participants With Untreated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
NCT05105841
COMPLETED
PHASE2
A Time-Limited Approach to Treatment With Ibrutinib for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
NCT04694560
WITHDRAWN
Acalabrutinib in Patients With Relapsed/Refractory and Treatment naïve Deletion 17p CLL/SLL
NCT02337829
COMPLETED
PHASE2
A Study of ACP-196 (Acalabrutinib) in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy
NCT02717611
ACTIVE_NOT_RECRUITING
PHASE2
CLL11: A Study of Obinutuzumab (RO5072759 [GA101]) With Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia (Stage 2)
NCT02053610
COMPLETED
PHASE3
Assessing the Ability of Combination Treatment With Venetoclax to Permit Time Limited Therapy in Chronic Lymphocytic Leukemia
NCT03701282
ACTIVE_NOT_RECRUITING
PHASE3
Zanubrutinib With Obinutuzumab in Untreated Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
NCT06544785
RECRUITING
PHASE2
Zanubrutinib, Obinutuzumab, and Sonrotoclax in Previously Untreated Patients With CLL or SLL
NCT06849713
RECRUITING
PHASE2
Study to Assess the Efficacy and Safety of Ublituximab and Umbralisib in Participants With Chronic Lymphocytic Leukemia (CLL) Currently Treated With Ibrutinib, Acalabrutinib or Venetoclax
NCT04016805
TERMINATED
PHASE2
A Multi-Center Study of Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Patients With Treatment naïve Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
NCT02264574
COMPLETED
PHASE3
Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia
NCT04075292
ACTIVE_NOT_RECRUITING
PHASE3