Venetoclax-Obinutuzumab +/- Acalabrutinib for R/R CLL/SLL
This study is testing a combination of drugs for people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that has returned or not responded to previous treatment. You would receive Venetoclax (a pill), Obinutuzumab (given through a vein), and possibly Acalabrutinib (a capsule). Venetoclax blocks a protein that helps cancer cells survive, Obinutuzumab targets and destroys cancer cells, and Acalabrutinib blocks another protein involved in cancer growth. The main goal is to see what percentage of participants are alive after one year. This study is looking for 40 participants and its current status is unclear. To join, you must have CLL or SLL requiring therapy and meet specific risk criteria based on your disease.
- Study design
- This is a Phase II interventional study, meaning it tests the safety and effectiveness of these investigational drugs. It plans to enroll 40 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoint measures participants alive at 1 year, suggesting follow-up for at least this duration.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04560322
Venetoclax-Obinutuzumab +/- Acalabrutinib in R/R CLL
Recruiting
PHASE2Ages 18+InterventionalTreatmentMassachusetts General HospitalInvestigator-initiated
~40 participants
Updated 2026-04-13 on ClinicalTrials.gov
What's tested:VenetoclaxObinutuzumabAcalabrutinib
At a glance
Recruiting sites
1 of 3 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Percentage of participants alive at 1 year
Measured over 1 year
Conditions
Where it's being run
3 sites across 1 statesMassachusetts3
Study leadership
- Jacob D Soumerai, MD · PRINCIPAL_INVESTIGATOR · Massachusetts General Hospital
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Diagnosis of CLL or SLL according to WHO criteria
Participants must require therapy according to iwCLL 2018 guidelines
Participants must have ≥ 2 points (high or intermediate risk disease) according to the CLL
Beta-2 microglobulin If ≥ 5 mg/L, assign 1 point
Lactate dehydrogenase If \>institutional upper limit of normal, assign 1 point
Hemoglobin If \<11 g/dL (female) or \<12 g/dL (male), assign 1 point
Time from start of last therapy If \<24 months, assign 1 point, If 4 points, patient is high risk, If 2-3 points, patient is intermediate risk, If 0-1 points, patient is low risk
Participants must have received prior systemic therapy for CLL
Age over 18 years
ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
Participants must have adequate organ function as defined below:
total bilirubin ≤2 × institutional upper limit of normal unless considered secondary to Gilbert's syndrome, in which case ≤3 x ULN
AST(SGOT)/ALT(SGPT) ≤2 × institutional upper limit of normal
creatinine within normal institutional limits OR
creatinine clearance ≥30 mL/min according to the Cockcroft-Gault Equation for participants with creatinine levels above institutional normal.
Participants must have adequate marrow function as defined below (unless clearly due to disease under study per investigator discretion)
absolute neutrophil count ≥1,000/mcL
platelets ≥75,000/mcL OR
\> 20,000/mcL if thrombocytopenia is clearly due to disease under study (per investigator discretion).
For females of childbearing potential, a negative serum pregnancy test within 7 days of study treatment
For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate \[\<1% per year\] when used consistently and correctly) and to continue its use for 90 days after the last dose of acalabrutinib or venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Willingness to not donate sperm or oocytes during the entire study treatment period and after treatment discontinuation
Ability to understand and the willingness to sign a written informed consent document.
Exclusion
Prior therapy with a BTK inhibitor (e.g. acalabrutinib) or BCL2 inhibitor (e.g. venetoclax), with the following exception:
Patients with undetectable MRD by flow cytometry at 10 (peripheral blood or bone marrow) or CR from prior treatment with BCL2 inhibitor (with or without BTK inhibitor) are eligible. Note: Patients who received prior BTK inhibitor therapy alone are not eligible.
Known hypersensitivity (IgE-mediated) reaction to obinutuzumab or to any of its excipients
Participants who are receiving any other investigational agents unless authorized by the overall study principal investigator
Known active histological transformation from CLL to an aggressive lymphoma (i.e., Richter's transformation)
Active malignancy or systemic therapy for another malignancy within 3 years; local/regional therapy with curative intent such as surgical resection or localized radiation within 3 years of treatment is permitted; active prostate cancer that is considered low-risk and appropriate for continued active surveillance strategy is permitted.
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
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 2 weeks prior to Cycle 1, Day 1
Known bleeding diathesis
Pregnant women are excluded from this study because the study agents have 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 the study agents, breastfeeding should be discontinued if the mother is treated with study therapy.
Prior major surgical procedure within 4 weeks of study, or anticipation of need for a major surgical procedure during the course of the study
Known CNS hemorrhage or stroke within 6 months of the study
History of progressive multifocal leukoencephalopathy (PML)
History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection
Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody \[HBcAb\] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to take appropriate anti-viral prophylaxis as indicated and undergo monthly DNA testing.
Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
Congestive heart failure, New York Heart Association classification III/IV
Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment
Known condition or other clinical situation that would affect oral absorption
Psychiatric illness/social situations that would interfere with study compliance
Receipt of therapy with strong inhibitors or inducers of CYP3A, CYP2C8, CYP2C9 and CYP2C19, within 7 days prior to the first dose of study drug administration
Consumption of grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study drug administration.
Requires dual antiplatelet therapy or anticoagulation with warfarin
What this trial measures
- Percentage of participants alive at 1 year1 year
Percent of participants with high and intermediate risk relapsed/refractory CLL who are alive at 1 year. The percent of patients who are alive at one-year (rOS) will be measured by monitoring you in clinic. An rOS of at least 90% will be considered promising whereas the rOS of 75% or less will be considered non-promising.