Chronic Lymphocytic LeukemiaPhase 2NCT04505254
Acalabrutinib and Obinutuzumab for the Treatment of Chronic Lymphocytic Leukemia
A Phase 2 study testing Acalabrutinib and Obinutuzumab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial investigates the how well acalabrutinib and obinutuzumab work in treating patients with chronic lymphocytic leukemia (CLL). Acalabrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
- What is being tested?
- Acalabrutinib and Obinutuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Aug 2020to 30 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis CLL/small lymphocytic lymphoma (SLL) and be untreated
- Patients must have an indication for treatment by 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patients of childbearing potential must be willing to practice highly effective birth control during treatment and for 2 days after the last dose of acalabrutinib or 18 months after the last dose of obinutuzumab, whichever is later
- A negative urine pregnancy test (within 7 days of day 1) is required for women with childbearing potential
- Adequate renal and hepatic function as indicated by all of the following: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) except for patients with bilirubin elevation due to Gilbert's disease who will be allowed to participate
Show all 9Show fewer
- An alanine transferase (ALT) =< 2.5 x ULN
- An estimated creatinine clearance (CrCl) of > 30 mL/min, as calculated by the Cockcroft-Gault equation unless disease related
- Free of prior malignancies for 2 years with exception of patients diagnosed with basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast who are eligible even if they are currently treated or have been treated and/or diagnosed in the past 2 years prior to study enrollment. If patients had another malignancy of indolent behavior in the past 2 years prior to study enrollment that is expected to be cured with treatment they received such patients can be enrolled, after consultation with the principal investigator
Who cannot join
- Pregnant or breast-feeding females
- Prior CLL/SLL treatment
- Known history of infection with human immunodeficiency virus (HIV) or any uncontrolled active significant infection (eg, bacterial, viral or fungal)
- Signs of active hepatitis B or C. Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
- Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP)
- Patients with severe hematopoietic insufficiency as defined by an absolute neutrophil count of less than 500/μL, unless disease-related, and/or a platelet count of less than 30,000/μL at time of screening for this protocol.
Show all 18Show fewer
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of heart failure, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Subjects with controlled, asymptomatic atrial fibrillation can enroll. Patients with a history of paroxysmal atrial fibrillation (PAF) or deep vein thrombosis or pulmonary embolism (DVT/PE) can be included if they had no signs of PAF or DVT/PE in the last 6 months before enrolment. Patients with ongoing atrial fibrillation (AFib) or ongoing PAF or DVT/PE should be excluded
- History of stroke or cerebral hemorrhage within 6 months
- Known history or evidence of bleeding diathesis or coagulopathy within 3 months
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 1. Bone marrow aspiration and/or biopsy are allowed
- Serious, non-healing wound, ulcer, or bone fracture
- Treatment with warfarin (Coumadin) or any other vitamin K antagonist. Patients who recently received warfarin must be off warfarin for at least 7 days prior to start of the study. Patients receiving novel oral anticoagulant (NOAC), also termed direct oral anticoagulant (DOAC) are permitted to enroll. Patients who are currently on a vitamin K antagonist must be switched to a non-vitamin K antagonist, such as a NOAC/DOAC
- Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
- Known history of drug-specific hypersensitivity or anaphylaxis to study drug (including active product or excipient components)
- Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer
- Prothrombin time (PT)/international normalized ratio (INR) or activated partial thromboplastin time (aPTT) (in the absence of lupus anticoagulant) > 2 x ULN
- Concurrent participation in another therapeutic clinical trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intermittent Therapy With the BTK Inhibitor Acalabrutinib (Calquence) in Combination With Obinutuzumab in Treatment Naive (Tn) Patients With Chronic Lymphocytic Leukemia (CLL)
This phase II trial investigates the how well acalabrutinib and obinutuzumab work in treating patients with chronic lymphocytic leukemia (CLL). Acalabrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib and obinutuzumab may help to control disease progression in CLL patients who have not received treatment for CLL.
Read the detailed description
PRIMARY OBJECTIVE:
- to determine the proportion of patients who have treatment-free remission 6 months after discontinuation of acalabrutinib plus obinutuzumab therapy.
SECONDARY OBJECTIVES:
- to determine clinical factors associated with a treatment-free remission of more than 6 months after discontinuation of acalabrutinib;
- to determine the treatment-free remission length;
- to evaluate the efficacy of re-treatment with acalabrutinib plus obinutuzumab in patients who experience disease relapse.
EXPLORATORY OBJECTIVES:
- to characterize the effects of limited duration acalabrutinib plus obinutuzumab therapy on the clonal architecture as determined by genome-wide genotyping and analysis (GWAs) and whole exome sequencing (WES) and to determine the frequency of BTK and PLCG2 mutation in patients relapsing after limited duration acalabrutinib plus obinutuzumab therapy.
OUTLINE:
Patients receive acalabrutinib orally (PO) twice a day (BID) every 12 hours starting on day 1 of cycle 1, and obinutuzumab intravenously (IV) over 4-6 hours on days 1 and 2 of cycle 3, and day 1 of cycles 4-8. Patients who do not achieve a complete response or remission after cycle 8 may receive single-agent acalabrutinib therapy PO BID for an additional 6 cycles at the discretion of their treating physician. Patients who are in partial response or who have stable disease receive an additional 6 cycles of acalabrutinib PO BID and obinutuzumab IV. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days then every 3 months.
- Being tested
- Acalabrutinib, Obinutuzumab
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Also called ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence
Given PO
ObinutuzumabBiological
Also called Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (acalabrutinib, obinutuzumab) | Experimental | Patients receive acalabrutinib PO BID every 12 hours starting on day 1 of cycle 1, and obinutuzumab IV over 4-6 hours on days 1 and 2 of cycle 3, and day 1 of cycles 4-8. Patients who do not achieve a complete response or remission after cycle 8 may receive single-agent acalabrutinib therapy PO BID for an additional 6 cycles at the discretion of their treating physician. Patients who are in partial response or who have stable disease receive an additional 6 cycles of acalabrutinib PO BID and obinutuzumab IV. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Acalabrutinib; Biological: Obinutuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-free remission
Defined as the time from discontinuation of acalabrutinib to the date of CLL relapse with active disease.
Measured: At 6 months after discontinuation of acalabrutinib, up to 4 years
Overall response rate
Defined as complete response
Measured: After 6 cycles (each cycle 28 days) of treatment,up to 4 years
Overall response rate
Defined as partial response
Measured: After 6 cycles (each cycle 28 days) of treatment,up to 4 years
Secondary outcomes (3)
Clinical factors associated with a treatment-free remission
Will use Cox's proportional hazards analysis of predictors that have a p value < 0.2 in the univariate analysis. Explanatory variables that were highly correlated will be independently entered into the Cox's regression model. Factors significant in at least one model tested will be taken to be possible independent predictors of relapse risk. Demographic and clinical characteristics will be summarized using descriptive statistics, including means with standard deviations, or medians with ranges, histograms and box-plot. Fisher's exact test and Wilcoxon rank test will be used in the data analyses of categorical and continuous variables, respectively.
Measured: Up to 6 months after completion of treatment
Treatment-free remission length
The median length of treatment-free remission will be estimated using the Kaplan-Meier method.
Measured: Up to 6 months after completion of treatment
Success rate of re-treatment in patients who relapse
The success rate of re-treatment, along with the 95% confidence interval will be computed, and median length of treatment-free remission will be estimated.
Measured: Up to 6 months after completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2020
- Study start25 Aug 2020
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jan A Burger, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04505254
- Sponsor's protocol ID
- 2019-1141
- Other IDs
- NCI-2020-05262, 2019-1141
- Status last verified
- Jun 2026
- First submitted
- 21 Jul 2020
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intermittent Therapy With the BTK Inhibitor Acalabrutinib (Calquence) in Combination With Obinutuzumab in Treatment Naive (Tn) Patients With Chronic Lymphocytic Leukemia (CLL)
- ClinicalTrials.gov ID
- NCT04505254
- Acronym / sponsor ID
- 2019-1141
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 25 Aug 2020 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 10 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial investigates the how well acalabrutinib and obinutuzumab work in treating patients with chronic lymphocytic leukemia (CLL). Acalabrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib and obinutuzumab may help to control disease progression in CLL patients who have not received treatment for CLL.
Detailed description
PRIMARY OBJECTIVE:
- to determine the proportion of patients who have treatment-free remission 6 months after discontinuation of acalabrutinib plus obinutuzumab therapy.
SECONDARY OBJECTIVES:
- to determine clinical factors associated with a treatment-free remission of more than 6 months after discontinuation of acalabrutinib;
- to determine the treatment-free remission length;
- to evaluate the efficacy of re-treatment with acalabrutinib plus obinutuzumab in patients who experience disease relapse.
EXPLORATORY OBJECTIVES:
- to characterize the effects of limited duration acalabrutinib plus obinutuzumab therapy on the clonal architecture as determined by genome-wide genotyping and analysis (GWAs) and whole exome sequencing (WES) and to determine the frequency of BTK and PLCG2 mutation in patients relapsing after limited duration acalabrutinib plus obinutuzumab therapy.
OUTLINE:
Patients receive acalabrutinib orally (PO) twice a day (BID) every 12 hours starting on day 1 of cycle 1, and obinutuzumab intravenously (IV) over 4-6 hours on days 1 and 2 of cycle 3, and day 1 of cycles 4-8. Patients who do not achieve a complete response or remission after cycle 8 may receive single-agent acalabrutinib therapy PO BID for an additional 6 cycles at the discretion of their treating physician. Patients who are in partial response or who have stable disease receive an additional 6 cycles of acalabrutinib PO BID and obinutuzumab IV. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days then every 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (acalabrutinib, obinutuzumab) | Experimental | Drug: Acalabrutinib, Biological: ObinutuzumabPatients receive acalabrutinib PO BID every 12 hours starting on day 1 of cycle 1, and obinutuzumab IV over 4-6 hours on days 1 and 2 of cycle 3, and day 1 of cycles 4-8. Patients who do not achieve a complete response or remission after cycle 8 may receive single-agent acalabrutinib therapy PO BID for an additional 6 cycles at the discretion of their treating physician. Patients who are in partial response or who have stable disease receive an additional 6 cycles of acalabrutinib PO BID and obinutuzumab IV. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Diagnosis CLL/small lymphocytic lymphoma (SLL) and be untreated
- Patients must have an indication for treatment by 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patients of childbearing potential must be willing to practice highly effective birth control during treatment and for 2 days after the last dose of acalabrutinib or 18 months after the last dose of obinutuzumab, whichever is later
- A negative urine pregnancy test (within 7 days of day 1) is required for women with childbearing potential
Key exclusion criteria (18 listed)
- Pregnant or breast-feeding females
- Prior CLL/SLL treatment
- Known history of infection with human immunodeficiency virus (HIV) or any uncontrolled active significant infection (eg, bacterial, viral or fungal)
- Signs of active hepatitis B or C. Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
- Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcalabrutinibAlso: ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, CalquenceGiven PO | Drug | Treatment (acalabrutinib, obinutuzumab) |
| ObinutuzumabAlso: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, GazyvaGiven IV | Biological | Treatment (acalabrutinib, obinutuzumab) |
Primary outcome
Treatment-free remission
Time frame: At 6 months after discontinuation of acalabrutinib, up to 4 years
Defined as the time from discontinuation of acalabrutinib to the date of CLL relapse with active disease.
Overall response rate
Time frame: After 6 cycles (each cycle 28 days) of treatment,up to 4 years
Defined as complete response
Overall response rate
Time frame: After 6 cycles (each cycle 28 days) of treatment,up to 4 years
Defined as partial response
3 secondary outcomes
Clinical factors associated with a treatment-free remission
Time frame: Up to 6 months after completion of treatment
Treatment-free remission length
Time frame: Up to 6 months after completion of treatment
Success rate of re-treatment in patients who relapse
Time frame: Up to 6 months after completion of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
Related trials for Chronic Lymphocytic Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan A Burger principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acalabrutinib and Obinutuzumab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-free remission (time frame: At 6 months after discontinuation of acalabrutinib, up to 4 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.