Chronic Lymphocytic LeukemiaPhase 2NCT04624633
Acalabrutinib, Umbralisib, and Ublituximab (AU2) In Relapsed and Untreated CLL
A Phase 2 study testing Acalabrutinib, Umbralisib and Ublituximab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Jennifer R. Brown, MD, PhD at 1 site in United States.
Trial summary
This study is testing the effectiveness of the study drug combination of acalabrutinib, umbralisib, and ublituximab in participants with Chronic Lymphocytic leukemia (CLL). The names of the study drugs involved in this study are/is: Acalabrutinib (CALQUENCE®, ACP-196) Umbralisib (TGR-1202) Ublituximab (TG-1101) 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, Relapsed Chronic Lymphocytic Leukemia
- What is being tested?
- Acalabrutinib, Umbralisib and Ublituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2020to 1 Jan 2028
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) per International Workshop on CLL (iwCLL) 2018 criteria.1
- Participants must have an indication for treatment as defined by iwCLL 2018 criteria.1
- Participants must have measurable disease, defined as lymphocytosis > 5,000 / μL, or palpable or CT measurable lymphadenopathy ≥ 1.5 cm, or bone marrow involvement ≥ 30%.
- For enrollment to Cohort 1: Participants must have relapsed or refractory disease as per iwCLL 2018 criteria,1 and must have received no more than 2 prior lines of anti-cancer therapy.
- For enrollment to Cohort 2: Participants must have previously untreated disease (i.e.
- must not have received any prior systemic therapy for CLL or SLL).
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- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of umbralisib, acalabrutinib, and ublituximab in participants < 18 years of age and CLL is extremely rare in this population, children are excluded from this study.
- ECOG performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix A).
- Participants must have adequate organ and marrow function as defined below:
- Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (unless due to hemolysis or Gilbert's disease, in which ≤ 3 × institutional ULN is acceptable)
- AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional ULN, OR
- AST (SGOT) and ALT (SGPT) ≤ 5 × institutional ULN if there is hemolysis or documented disease involvement in the liver
- Calculated creatinine clearance ≥ 30 mL/min (as calculated by the Cockcroft-Gault formula)
- Platelet count ≥ 50,000/mcL, unless there is bone marrow involvement with disease
- PT-INR or aPTT ≤ 2 × institutional ULN
- Absolute neutrophil count (ANC) ≥ 750 mm3
- Hemoglobin (Hgb) > 8 g/dL
- Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
- The effects of umbralisib, acalabrutinib, or ublituximab on the developing human fetus are unknown. For this reason and because anti-cancer agents are known to be teratogenic, women of child-bearing potential and men must agree to use highly effective methods of contraception. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated on this protocol must agree to use highly effective contraception prior to the study, for the duration of study participation, and 4 months after completion of umbralisib, acalabrutinib, or ublituximab administration.
- Ability to understand and the willingness to sign a written informed consent document.
- Ability to swallow and retain oral medication.
- Participants must be able to receive prophylactic anti-pneumocystis jiroveci pneumonia (PJP) and anti-viral therapy
Who cannot join
- Participants with progressive or refractory disease while receiving either a BTK inhibitor or PI3K inhibitor. Prior exposure to either a BTK inhibitor, PI3K inhibitor, or both is acceptable as long as the participant's disease did not progress during active therapy with the agent(s).
- Participants who have undergone a major surgical procedure within 28 days of the first dose of study drug. If a participant had major surgery greater than 28 days prior to the first dose of study drug, they must have recovered adequately from any adverse event and/or complications from the intervention prior to the first dose (as judged by the treating investigator). For enrollment to Cohort 1: receipt of prior BTK inhibitor treatment within 7 days, or any other anti-cancer therapy (e.g. chemotherapy, immunotherapy, radiation, biologic therapy or any investigational agent) within 21 days of the first dose of study drug.
- Participants who are receiving any other investigational agents.
- History of prior allogeneic stem cell transplant.
- History of autologous hematologic stem cell transplant within 6 months of the first dose of study drug.
- Participants with known Richter's transformation, or histological transformation from CLL to large cell lymphoma.
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- Participants with known CNS involvement, because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with no known history of CNS leukemia are not required to undergo CT scan or lumbar puncture (LP) for trial eligibility unless the participant is symptomatic as judged by the treating investigator.
- Participants with uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
- Participants with active clinically significant bleeding or history of bleeding diathesis (e.g. hemophilia or von Willebrand disease).
- Participants requiring or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (other anticoagulants are permitted).
- Participants with a history of significant cerebrovascular disease/event within 6 months before the first dose of study drug, including stroke or intracranial hemorrhage.
- Participants with uncontrolled intercurrent illness, including but not limited to: unstable angina pectoris, cardiac arrhythmia, or poorly controlled and clinically significant atherosclerotic vascular disease (including patients who required angioplasty, cardiac or vascular stenting within 6 months prior to the first dose of study agent), myocardial infarction within 6 months of screening, congestive heart failure, or patients with Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Note: participants with controlled, asymptomatic atrial fibrillation are permitted to enroll on study. Concomitant use of medication known to cause QT prolongation or torsades de pointes should be used with caution and at investigator discretion.
- Individuals with a history of a different malignancy are ineligible with the following exceptions: individuals who have been treated and are disease-free for a minimum of 2 years prior to study enrollment, or individuals who are deemed by the treating investigator to be at low risk for disease recurrence. Additionally, individuals with the following cancers are eligible if diagnosed and curatively treated within the past 2 years: basal or squamous cell carcinomas of the skin, and breast or cervical carcinomas in situ.
- Prostate cancer on observation, with stable PSA for 6 months, is also eligible.
- Participants who require ongoing immunosuppressive therapy including systemic corticosteroids (prednisone or equivalent ≤ 10 mg daily is permitted). Topical, inhaled, and ophthalmologic steroids are permitted.
- Participants with a history of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis).
- Participants with irritable bowel syndrome (IBS) with greater than 3 loose stools per day at baseline.
- Participants with evidence of ongoing systemic bacterial, fungal, or viral infection, except localized fungal infections of the skin or nails. NOTE: participants may be receiving prophylactic antiviral or antibacterial therapies at the treating investigator's discretion. Use of anti-pneumocystis and antiviral prophylaxis is required.
- Participants with a known history of progressive multifocal leukoencephalopathy (PML).
- Participants with evidence of chronic active Hepatitis B (HBV, not including patients with prior hepatitis B vaccination or positive serum Hepatitis B antibody), chronic active
- Hepatitis C infection (HCV), active cytomegalovirus (CMV), or known history of human immunodeficiency virus (HIV):
- If HBc antibody is positive, the subject must be evaluated for the presence of HBV DNA by PCR (see Appendix B). Subjects with positive HBc antibody and negative HBV DNA by PCR are eligible but serial monitoring of HBV DNA by PCR is required, see Section 5.4. Subjects with positive HBV DNA by PCR are not eligible.
- Participants with positive HBsAg are to be excluded.
- If HCV antibody is positive, the subject must be evaluated for the presence of HCV RNA by PCR. Subjects with positive HCV antibody and negative HCV RNA by PCR are eligible. Subjects with positive HCV RNA by PCR are not eligible.
- If the subject is CMV IgG or CMV IgM positive, the subject must be evaluated for the presence of CMV DNA by PCR. Subjects who are CMV IgG or CMV IgM positive but who are CMV DNA negative by PCR are eligible, anti-viral prophylaxis should be considered per treating investigator discretion.
- History of allergic reactions attributed to study drugs including active product or excipients, or compounds of similar chemical or biologic composition to acalabrutinib, umbralisib, or ublituximab, including participants with a history of anaphylaxis (excluding infusion-related reactions) in association with previous anti-CD20 administration.
- Participants requiring concomitant treatment with any medications or substances that are strong inhibitors or inducers of CYP3A4 at the time of study enrollment. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
- Participants requiring concomitant treatment with proton pump inhibitors (e.g.omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole) at the time of study enrollment. Note: participants receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids prior to the first dose of study medication are eligible.
- Participants with psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because acalabrutinib, umbralisib, and ublituximab are anti-cancer agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with acalabrutinib, umbralisib, or ublituximab, breastfeeding must be discontinued prior to the initiation of study treatment. A negative serum pregnancy test is required for women of childbearing potential within 3 days prior to Cycle 1 Day 1.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase 2 Study of Acalabrutinib, Umbralisib, and Ublituximab (AU2) in Relapsed and Previously Untreated CLL Patients
This study is testing the effectiveness of the study drug combination of acalabrutinib, umbralisib, and ublituximab in participants with Chronic Lymphocytic leukemia (CLL).
The names of the study drugs involved in this study are/is:
- Acalabrutinib (CALQUENCE®, ACP-196)
- Umbralisib (TGR-1202)
- Ublituximab (TG-1101)
Read the detailed description
In this research study, Investigators are exploring the combination of acalabrutinib, umbralisib, and ublituximab and hoping to determine if the combination is effective at controlling cancer growth in participants with CLL.
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
Participants will receive the study drugs for a maximum of 24 cycles (2 years) and will be followed for a maximum of 5 years after discontinuing the study drugs.
The names of the study drugs involved in this study are/is:
- Acalabrutinib (CALQUENCE®, ACP-196)
- Umbralisib (TGR-1202)
- Ublituximab (TG-1101)
It is expected that about 60 people will take part in this research study.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drugs to learn whether the drugs work in treating a specific disease. "Investigational" means that the drugs are being studied.
- The U.S. Food and Drug Administration (FDA) has not approved umbralisib or ublituximab as a treatment for any disease.
- The U.S. Food and Drug Administration (FDA) has approved acalabrutinib for CLL, but not in this combination.
- Acalabrutinib is a type of drug called a kinase inhibitor. It blocks a type of protein called Bruton Tyrosine Kinase (BTK) that helps CLL cells live and grow. By blocking BTK, acalabrutinib may kill cancer cells or stop them from growing.
- Umbralisib is an investigational drug which blocks a protein called PI3K. PI3K is a protein that helps CLL cells grow.
- Ublituximab is a type of investigational drug called a monoclonal antibody. A monoclonal antibody is a type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. By binding to the tumor cells, the antibody might prevent the tumor cell from growing and spreading.
As of March 2023, TG therapeutics has decided to no longer provide umbralisib, ublituximab and funding for this study. Study participants still on treatment will still have access to acalabrutinib.
- Conditions
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Relapsed Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia
- Being tested
- Acalabrutinib, Umbralisib, Ublituximab
- Keywords
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Relapsed Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia
- 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 Calquence
Oral, twice a day, predetermined dosage
UmbralisibDrug
Also called RP5264
Oral, once a day, predetermined dosage, each 28 day cycle up to 24 cycles
UblituximabDrug
Also called LFB-R603
28 day cycle, starting cycle 7 via iv, on at predetermined dosage and timepoints in each cycle
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1-Relapsed Disease | Experimental | Participants with relapsed disease
* Treatment with Acalabrutinib \& Umbralisib beginning C1D1,
* Ublituximab beginning C7D1
* Assessment of treatment response
* Treatment continues for a maximum of 24 cycles. Participants followed post treatment for a maximum of 5 years Receives: Drug: Acalabrutinib; Drug: Umbralisib; Drug: Ublituximab |
| Cohort 2-Treatment Naive | Experimental | Participants with previously untreated disease
* Treatment with Acalabrutinib \& Umbralisib beginning C1D1,
* Ublituximab beginning C7D1
* Assessment of treatment response
* Treatment continues for a maximum of 24 cycles. Participants followed post treatment for a maximum of 5 years Receives: Drug: Acalabrutinib; Drug: Umbralisib; Drug: Ublituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission (CR) Rate After 24 Cycles
The CR Rate is defined as the proportion of participants achieving complete remission (CR) based on 2018 IW-CLL criteria.
Measured: According to this endpoint is after 24 cycles. Overall median number of cycles is 24 with range 1-25.
Secondary outcomes (2)
Partial Remission (PR) Rate After 24 Cycles
The PR Rate is defined as the proportion of participants achieving partial remission (PR) based on 2018 IW-CLL criteria.
Measured: According to this endpoint is after 24 cycles. Overall median number of cycles is 24 with range 1-25.
Median Progression-Free Survival (PFS)
Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last dsease assessment.
Measured: Disease will be evaluated through imaging at cycle 1 day 1, 8, and 15, cycle 2-6 and cycle 8-25 day 1, and cycle 7 day 1, 2 and 8. Observation on treatment up to approximately 25 cycles. In long-term follow-up, survival follow-up up to 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2020
- Study start15 Dec 2020
- Primary completion21 Dec 2023
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jennifer R. Brown, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, TG Therapeutics, Inc.
- Responsible party
- Sponsor-investigator, Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute
- Investigators
- Jennifer R Brown, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04624633
- Sponsor's protocol ID
- 20-394
- Status last verified
- Feb 2026
- First submitted
- 5 Nov 2020
- Last updated
- 25 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Publications
Yin Y, Xu H, He L, Brown JR, Mato AR, Aittokallio T, Skanland SS. Protein Profiles Predict Treatment Responses to the PI3K Inhibitor Umbralisib in Patients with Chronic Lymphocytic Leukemia. Clin Cancer Res. 2025 May 15;31(10):1943-1955. doi: 10.1158/1078-0432.CCR-24-2911.
PubMed 40085050
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Acalabrutinib, Umbralisib, and Ublituximab (AU2) in Relapsed and Previously Untreated CLL Patients
- ClinicalTrials.gov ID
- NCT04624633
- Acronym / sponsor ID
- 20-394
- Conditions
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Relapsed Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia
- Keywords
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Relapsed Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Jennifer R. Brown, MD, PhDUniversity, hospital or other
- Collaborators
- AstraZeneca, TG Therapeutics, Inc.
- Study start
- 15 Dec 2020 (actual)
- Primary completion
- 21 Dec 2023 (actual)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 12 Nov 2020 (actual)
- Results
- Posted 27 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is testing the effectiveness of the study drug combination of acalabrutinib, umbralisib, and ublituximab in participants with Chronic Lymphocytic leukemia (CLL).
The names of the study drugs involved in this study are/is:
- Acalabrutinib (CALQUENCE®, ACP-196)
- Umbralisib (TGR-1202)
- Ublituximab (TG-1101)
Detailed description
In this research study, Investigators are exploring the combination of acalabrutinib, umbralisib, and ublituximab and hoping to determine if the combination is effective at controlling cancer growth in participants with CLL.
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
Participants will receive the study drugs for a maximum of 24 cycles (2 years) and will be followed for a maximum of 5 years after discontinuing the study drugs.
The names of the study drugs involved in this study are/is:
- Acalabrutinib (CALQUENCE®, ACP-196)
- Umbralisib (TGR-1202)
- Ublituximab (TG-1101)
It is expected that about 60 people will take part in this research study.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drugs to learn whether the drugs work in treating a specific disease. "Investigational" means that the drugs are being studied.
- The U.S. Food and Drug Administration (FDA) has not approved umbralisib or ublituximab as a treatment for any disease.
- The U.S. Food and Drug Administration (FDA) has approved acalabrutinib for CLL, but not in this combination.
- Acalabrutinib is a type of drug called a kinase inhibitor. It blocks a type of protein called Bruton Tyrosine Kinase (BTK) that helps CLL cells live and grow. By blocking BTK, acalabrutinib may kill cancer cells or stop them from growing.
- Umbralisib is an investigational drug which blocks a protein called PI3K. PI3K is a protein that helps CLL cells grow.
- Ublituximab is a type of investigational drug called a monoclonal antibody. A monoclonal antibody is a type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. By binding to the tumor cells, the antibody might prevent the tumor cell from growing and spreading.
As of March 2023, TG therapeutics has decided to no longer provide umbralisib, ublituximab and funding for this study. Study participants still on treatment will still have access to acalabrutinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1-Relapsed Disease | Experimental | Drug: Acalabrutinib, Drug: Umbralisib, Drug: UblituximabParticipants with relapsed disease * Treatment with Acalabrutinib \& Umbralisib beginning C1D1, * Ublituximab beginning C7D1 * Assessment of treatment response * Treatment continues for a maximum of 24 cycles. Participants followed post treatment for a maximum of 5 years |
| Cohort 2-Treatment Naive | Experimental | Drug: Acalabrutinib, Drug: Umbralisib, Drug: UblituximabParticipants with previously untreated disease * Treatment with Acalabrutinib \& Umbralisib beginning C1D1, * Ublituximab beginning C7D1 * Assessment of treatment response * Treatment continues for a maximum of 24 cycles. Participants followed post treatment for a maximum of 5 years |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) per International Workshop on CLL (iwCLL) 2018 criteria.1
- Participants must have an indication for treatment as defined by iwCLL 2018 criteria.1
- Participants must have measurable disease, defined as lymphocytosis > 5,000 / μL, or palpable or CT measurable lymphadenopathy ≥ 1.5 cm, or bone marrow involvement ≥ 30%.
- For enrollment to Cohort 1: Participants must have relapsed or refractory disease as per iwCLL 2018 criteria,1 and must have received no more than 2 prior lines of anti-cancer therapy.
- For enrollment to Cohort 2: Participants must have previously untreated disease (i.e.
Key exclusion criteria (30 listed)
- Participants with progressive or refractory disease while receiving either a BTK inhibitor or PI3K inhibitor. Prior exposure to either a BTK inhibitor, PI3K inhibitor, or both is acceptable as long as the participant's disease did not progress during active therapy with the agent(s).
- Participants who have undergone a major surgical procedure within 28 days of the first dose of study drug. If a participant had major surgery greater than 28 days prior to the first dose of study drug, they must have recovered adequately from any adverse event and/or complications from the intervention prior to the first dose (as judged by the treating investigator). For enrollment to Cohort 1: receipt of prior BTK inhibitor treatment within 7 days, or any other anti-cancer therapy (e.g. chemotherapy, immunotherapy, radiation, biologic therapy or any investigational agent) within 21 days of the first dose of study drug.
- Participants who are receiving any other investigational agents.
- History of prior allogeneic stem cell transplant.
- History of autologous hematologic stem cell transplant within 6 months of the first dose of study drug.
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: CalquenceOral, twice a day, predetermined dosage | Drug | Cohort 1-Relapsed Disease, Cohort 2-Treatment Naive |
| UmbralisibAlso: RP5264Oral, once a day, predetermined dosage, each 28 day cycle up to 24 cycles | Drug | Cohort 1-Relapsed Disease, Cohort 2-Treatment Naive |
| UblituximabAlso: LFB-R60328 day cycle, starting cycle 7 via iv, on at predetermined dosage and timepoints in each cycle | Drug | Cohort 1-Relapsed Disease, Cohort 2-Treatment Naive |
Primary outcome
Complete Remission (CR) Rate After 24 Cycles
Time frame: According to this endpoint is after 24 cycles. Overall median number of cycles is 24 with range 1-25.
The CR Rate is defined as the proportion of participants achieving complete remission (CR) based on 2018 IW-CLL criteria.
2 secondary outcomes
Partial Remission (PR) Rate After 24 Cycles
Time frame: According to this endpoint is after 24 cycles. Overall median number of cycles is 24 with range 1-25.
Median Progression-Free Survival (PFS)
Time frame: Disease will be evaluated through imaging at cycle 1 day 1, 8, and 15, cycle 2-6 and cycle 8-25 day 1, and cycle 7 day 1, 2 and 8. Observation on treatment up to approximately 25 cycles. In long-term follow-up, survival follow-up up to 5 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40085050Yin Y, Xu H, He L, Brown JR, Mato AR, Aittokallio T, Skanland SS. Protein Profiles Predict Treatment Responses to the PI3K Inhibitor Umbralisib in Patients with Chronic Lymphocytic Leukemia. Clin Cancer Res. 2025 May 15;31(10):1943-1955. doi: 10.1158/1078-0432.CCR-24-2911.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
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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.
Jennifer R Brown, MD, PhD principal investigator
Dana-Farber Cancer Institute
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, Umbralisib and Ublituximab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Jennifer R. Brown, MD, PhD 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 22 inclusion and 30 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 25 Feb 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?
Yes. Results are posted in the registry (first posted 27 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Complete Remission (CR) Rate After 24 Cycles (time frame: According to this endpoint is after 24 cycles. Overall median number of cycles is 24 with range 1-25.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04624633, which also lists 1 linked publication.
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 25 Feb 2026.