Acalabrutinib with or without Obinutuzumab for early-stage Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Official title: Randomized Phase 2 Study Comparing Acalabrutinib to Acalabrutinib and Obinutuzumab in the Treatment of Patients With Early-Stage Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Who Are at High Risk of Disease Progression
Run by Mayo Clinic · NCT03516617 · Data updated 2026-11-12
This study is testing whether a new drug called acalabrutinib, alone or with another drug called obinutuzumab, can help people with early-stage chronic lymphocytic leukemia or small lymphocytic lymphoma feel better and live longer.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 120 (estimated) |
| Sponsor | Mayo Clinic Academic / other |
| Drugs / interventions | ibrutinib, chemotherapy, obinutuzumab, acalabrutinib, Immunotherapy |
| Locations | 3 sites (Scottsdale, Arizona and 2 other locations) |
| Status | Recruiting |
| Started | September 10, 2018 |
| Main results expected | November 11, 2028 |
| Study ends | November 11, 2036 |
| Registry record updated | October 26, 2026 |
| Trial ID | NCT03516617 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates include adults aged 18 and older with untreated, biopsy-proven CLL or SLL who meet specific risk criteria.
✕Probably not a fit
Patients with prior treatment for CLL or SLL or those with mantle cell lymphoma may not benefit from this study.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This phase II trial investigates the effectiveness of acalabrutinib, both alone and in combination with obinutuzumab, in treating patients with early-stage chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study aims to compare the rates of minimal residual disease-negative complete response and evaluate various outcomes such as overall response rate and progression-free survival. Participants will be assessed for safety and quality of life, and their immune profiles will be analyzed to understand the treatment's impact on immune response.
Why it matters
Potential benefit: If successful, this treatment approach could improve outcomes for patients with early-stage CLL or SLL by enhancing response rates and prolonging survival.
How similar studies have gone: Other studies have shown promise with similar therapies, suggesting potential for success in this approach.
Who can join: the full rules
Show full inclusion / exclusion criteria
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
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
Where it's running
-
Mayo Clinic in Arizona
Scottsdale, Arizona, United States Recruiting -
Mayo Clinic in Rochester
Rochester, Minnesota, United States Recruiting -
Mayo Clinic in Florida
Jacksonville, Florida, United States Active not recruiting
Study contacts
- Principal investigator: Sameer A. Parikh, M.D. — Mayo Clinic in Rochester
- Study coordinator: Clinical Trials Referral Office
- Email: mayocliniccancerstudies@mayo.edu
- Phone: 855-776-0015
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
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Acalabrutinib combined with venetoclax or obinutuzumab for treating chronic lymphocytic leukemia
This study is testing if a new combination of two drugs, acalabrutinib with either venetoclax or obinutuzumab, can help people with chronic lymphocytic leukemia who haven't been treated before by reducing cancer cells in their bone marrow.
-
Tafasitamab plus Acalabrutinib and Venetoclax for newly treated CLL/SLL
This phase II study tests a combination of tafasitamab, acalabrutinib, and venetoclax in adults who are newly diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma to see if it is safe and effective.
-
Venetoclax plus obinutuzumab followed by epcoritamab for untreated CLL/SLL
This trial tests whether giving venetoclax and obinutuzumab followed by epcoritamab can produce deep remissions in people with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.
-
Epcoritamab given after 2nd-generation BTK inhibitors for CLL/SLL
This trial will try giving subcutaneous epcoritamab for up to 12 cycles to adults with CLL/SLL who have been on a second‑generation BTK inhibitor for at least 12 months to see if it can deepen responses to a complete remission with undetectable MRD so therapy can be stopped.
-
Intermittent versus continuous venetoclax with acalabrutinib in CLL/SLL
This will test whether giving venetoclax intermittently or continuously together with acalabrutinib helps people with previously untreated CLL or SLL.
-
LP-168 plus obinutuzumab for previously treated and BTK T474I‑mutated CLL/SLL
This trial tests whether adding LP-168 to obinutuzumab helps people with previously treated CLL/SLL, including those with the BTK T474I gatekeeper mutation, achieve deeper remissions.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.