Recruiting
Phase 2

Venetoclax & Obinutuzumab

Sponsor:

Massachusetts General Hospital

Code:

NCT04560322

Conditions

Chronic Lymphocytic Leukemia

Small Lymphocytic Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Venetoclax

Obinutuzumab

Acalabrutinib

Study Details

Brief summary:

This research study is studying a combination of drugs as a possible treatment for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The names of the study drugs involved in this study are:

  • obinutuzumab
  • venetoclax
  • acalabrutinib

Conditions

Chronic Lymphocytic Leukemia

Small Lymphocytic Lymphoma

Study ID

NCT04560322

Start date

Oct 19, 2020

Status verified date

Apr, 2026

Completion date

Mar 1, 2029

Anticipated

Primary completion date

Mar 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

BALL Risk Model:

  • 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 Criteria:

  • 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

Study Design

Enrollment

40 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Venetoclax-Obinutuzumab +/- Acalabrutinib

A treatment cycle is defined as 28 consecutive days. Participants with undetectable MRD (uMRD) at 1 year will complete an additional 1 year of VO then stop therapy.

Participants with high detectable MRD at 1 year will complete an additional 1 year of VO plus acalabrutinib then stop therapy.

Participants with low detectable MRD at 1 year will complete an additional 1 year of VO alone. If this eradicates MRD, they will stop therapy. If there is still residual MRD, they will complete an additional 1 year of IVO then stop therapy.

If progression occurs on VO, I will be added and IV will be administered indefinitely. After 2 years, V may be stopped and I continued as monotherapy at investigator discretion.

  • Infused Study Drug: Obinutuzumab on Days 1, 2, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 1-6
  • Oral Study Drugs: Venetoclax daily starting on Cycle 1 Day 22
  • Oral Drug: acalabrutinib daily for Days 1-28 (if applicable)

Interventions

Venetoclax

Tablet, taken by mouth

Obinutuzumab

Intravenous infusion

Acalabrutinib

Capsule, taken by mouth

Primary outcome measure

  • Percentage of participants alive at 1 year [ Time Frame: 1 year ]

Central Contacts and Locations

Central contacts

Jacob D Soumerai, MD

617-724-4000jsoumerai@mgh.harvard.edu

Jacob D Soumerai, MD

jsoumerai@mgh.harvard.edu

Locations

Massachusetts General Hospital Cancer Center

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Jacob D Soumerai, MD

617-724-4000jsoumerai@mgh.harvard.edu

Principal Investigator:

Jacob D Soumerai, MD

More Information

Sponsor

Massachusetts General Hospital

Last update posted

Apr 13, 2026

Last verified

Apr, 2026

Keywords

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Massachusetts General Hospital on 2026-04-13.