Chronic Lymphocytic LeukemiaPhase 2NCT07690891
Nemtabrutinib With Venetoclax and Obinutuzumab in Patients With Chronic Lymphocytic Leukemia
A Phase 2 study testing Nemtabrutinib, Venetoclax and Obinutuzumab in people with Chronic Lymphocytic Leukemia, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
This is a single-arm, open-label Phase 2 study designed to evaluate the treatment outcomes of nemtabrutinib-venetoclax-obinutuzumab as a frontline management for chronic lymphocytic leukemia (CLL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Nemtabrutinib, Venetoclax and Obinutuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to 1 Sep 2031
- 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
- Patients aged 18 years or older.
- Patients must have a diagnosis of CLL/ Small Lymphocytic Lymphoma (SLL)
- Patients must meet International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for treatment initiation.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patient must meet the following screening clinical laboratory values as specified below:
- Hematologic: Absolute Neutrophil Count (ANC) of at least 1000 and platelet count of at least 50,000 unless these blood counts are low due to bone marrow involvement by CLL/SLL (use of growth factors, transfusions allowed to meet this criteria as clinically indicated).
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- International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × Upper Limit of Normal (ULN) unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
- Hepatic:
- Total bilirubin ≤1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN. Patients with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits and total bilirubin ≤3 x ULN).
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN.
- Renal: Creatinine clearance of at least 30 mL/min based either on Cockroft-Gault estimate or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or urine collection (12 or 24 hour).
- Patient is able to swallow oral medications.
- Female subjects who:
- Are postmenopausal for at least one year before the screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential:
- Agree to practice one highly effective method and one additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through six months after the last dose of study drug (female and male condoms should not be used together), OR ii. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception).
- Agree to not to donate or freeze egg(s) during the course of this study or within 180 days after receiving their last dose of study drug.
- Male subjects, even if surgically sterilized (i.e., status post vasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment period from the time of signing the informed consent through and through six months after the last dose of study drug (female and male condoms should not be used together), OR
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods for the female partner] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
- Agree to not to donate or freeze sperm during the course of this study or within 180 days after receiving their last dose of study drug.
- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable Hepatitis B (HBV) viral load at screening.
- Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests should include HBsAg and anti-HBV.
- Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable at screening. Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
- Participants with HIV are eligible if they meet ALL of the following criteria:
- The CD4 count is >350 cells/µL at screening
- The HIV viral load is below the detectable level as per locally available testing
- Are on a stable antiretroviral therapy (ART) regimen for at least 4 weeks prior to study entry i. Note: ART must include drugs which are NOT strong CYP3A4 inducers (participants receiving ART that are strong CYP3A4 inducers are not eligible to be included in the study).
- HIV screening tests are not required unless known history of HIV infection
- Ability to understand a written informed consent document, and the willingness to sign it.
Who cannot join
- Active HBV/HCV infection. See inclusion criteria 9 (HBV) and 10 (HCV) for requirements.
- Gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy).
- Diagnosis of Richter Transformation
- Active central nervous system (CNS) involvement
- Active infection requiring systemic therapy, including IV antibiotics during screening. Participants may be rescreened followed completion of IV antibiotic course.
- AIDS defining opportunistic infection in the past 12 months prior to screening.
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- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Clinically significant cardiac issues (unless patient has a pacemaker) such as QTc prolongation (defined as a QTcF >480 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree AV block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
- Known allergy/sensitivity to nemtabrutinib or any of the excipients
- History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding.
- History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years or no active therapy is needed.
- NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder.
- A person of childbearing potential who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
- Prior/Concomitant Therapy
- Prior use of any BTKi or Bcl2 inhibitor
- Currently being treated with the following drugs:
- P-gp substrates with a narrow therapeutic index
- CYP3A strong inducers
- CYP3A strong inhibitors NOTE: A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a participant to be eligible for study enrollment.
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (if prior therapy was a monoclonal antibody) or 5 half-lives before randomization, whichever is longer.
- Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids.
- Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.
- Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
- Prior/Concurrent Clinical Study Experience
- Is currently enrolled on another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited.
- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
- Diagnostic Assessments
- Has not adequately recovered after 4 weeks from major surgery or has ongoing surgical complications.
- Note: Biopsy and placement of central venous access devices are not considered major surgery.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Medical College of Wisconsin Cancer Center Clinical Trials Office contact
United States1 site
Froedtert & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Guru Guru Murthy, MD, 414-805-4600, gmurthy@mcw.edu
About this study
Official title: Phase II Study of Nemtabrutinib With Venetoclax and Obinutuzumab in Patients With Chronic Lymphocytic Leukemia
This is a single-arm, open-label Phase 2 study designed to evaluate the treatment outcomes of nemtabrutinib-venetoclax-obinutuzumab as a frontline management for chronic lymphocytic leukemia (CLL).
Read the detailed description
The primary objective of this study is to determine the rate of undetectable minimal residual disease (MRD) with this therapy. Secondary objectives include assessment of response, adverse event profile, and survival. Patients with treatment-naïve CLL who meet the eligibility criteria would be initiated on treatment as described below.
Patients will start nemtabrutinib monotherapy for the first 3 cycles, followed by the addition of obinutuzumab for 6 cycles (during Cycles 4-9) and venetoclax for 12 cycles (during Cycles 4-15) while continuing nemtabrutinib, for a total duration of 15 cycles of combined therapy.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Nemtabrutinib, Venetoclax, Obinutuzumab
- Keywords
- minimal residual disease
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NemtabrutinibDrug
Also called MK-1026
45 mg daily for 15 28-day cycles.
VenetoclaxDrug
Also called Venclexta, Venclyxto
Cycle 4, Days 1-7: 20 mg; Cycle 4, Days 8-14: 50 mg; Cycle 4, Days 15-21: 100 mg; Cycle 4, Days 22-28: 200 mg; Cycle 5-15: 400 mg.
ObinutuzumabDrug
Also called Gazyva
Cycle 4, Day 1: 100 mg; Cycle 4, Day 2: 900 mg; Cycle 4, Day 8: 1000 mg; Cycle 4, Day 15: 1000 mg; Cycles 5-9, Day 1: 1000 mg.
| Study group | Role | What they receive |
|---|---|---|
| Nemtabrutinib with Venetoclax and Obinutuzumab | Experimental | * Nemtabrutinib will be administered orally.
* Venetoclax will be administered orally
* Obinutuzumab will be administered intravenously. Receives: Drug: Nemtabrutinib; Drug: Venetoclax; Drug: Obinutuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Undetectable MRD
This measure is the proportion of subjects with undetectable MRD at 10^-4 sensitivity level by flow cytometry after treatment with nemtabrutinib, venetoclax, and obinutuzumab for frontline management of CLL.
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2026
- Study start1 Oct 2026 (estimated)
- Primary completion1 Dec 2029 (estimated)
- Study completion1 Sep 2031 (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 Medical College of WisconsinThe 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guru Subramanian Guru Murthy, Medical College of Wisconsin
- Investigators
- Guru S Guru Murthy, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07690891
- Sponsor's protocol ID
- IIT-GURU-NEMTABRUTINIB-CLL
- Status last verified
- Jul 2026
- First submitted
- 1 Jul 2026
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Nemtabrutinib With Venetoclax and Obinutuzumab in Patients With Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT07690891
- Acronym / sponsor ID
- IIT-GURU-NEMTABRUTINIB-CLL
- Conditions
- Chronic Lymphocytic Leukemia
- Keywords
- minimal residual disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 1 Dec 2029 (estimated)
- Study completion
- 1 Sep 2031 (estimated)
- First posted
- 8 Jul 2026 (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 is a single-arm, open-label Phase 2 study designed to evaluate the treatment outcomes of nemtabrutinib-venetoclax-obinutuzumab as a frontline management for chronic lymphocytic leukemia (CLL).
Detailed description
The primary objective of this study is to determine the rate of undetectable minimal residual disease (MRD) with this therapy. Secondary objectives include assessment of response, adverse event profile, and survival. Patients with treatment-naïve CLL who meet the eligibility criteria would be initiated on treatment as described below.
Patients will start nemtabrutinib monotherapy for the first 3 cycles, followed by the addition of obinutuzumab for 6 cycles (during Cycles 4-9) and venetoclax for 12 cycles (during Cycles 4-15) while continuing nemtabrutinib, for a total duration of 15 cycles of combined therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nemtabrutinib with Venetoclax and Obinutuzumab | Experimental | Drug: Nemtabrutinib, Drug: Venetoclax, Drug: Obinutuzumab* Nemtabrutinib will be administered orally. * Venetoclax will be administered orally * Obinutuzumab will be administered intravenously. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Patients aged 18 years or older.
- Patients must have a diagnosis of CLL/ Small Lymphocytic Lymphoma (SLL)
- Patients must meet International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for treatment initiation.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patient must meet the following screening clinical laboratory values as specified below:
Key exclusion criteria (31 listed)
- Active HBV/HCV infection. See inclusion criteria 9 (HBV) and 10 (HCV) for requirements.
- Gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy).
- Diagnosis of Richter Transformation
- Active central nervous system (CNS) involvement
- Active infection requiring systemic therapy, including IV antibiotics during screening. Participants may be rescreened followed completion of IV antibiotic course.
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 |
|---|---|---|
| NemtabrutinibAlso: MK-102645 mg daily for 15 28-day cycles. | Drug | Nemtabrutinib with Venetoclax and Obinutuzumab |
| VenetoclaxAlso: Venclexta, VenclyxtoCycle 4, Days 1-7: 20 mg; Cycle 4, Days 8-14: 50 mg; Cycle 4, Days 15-21: 100 mg; Cycle 4, Days 22-28: 200 mg; Cycle 5-15: 400 mg. | Drug | Nemtabrutinib with Venetoclax and Obinutuzumab |
| ObinutuzumabAlso: GazyvaCycle 4, Day 1: 100 mg; Cycle 4, Day 2: 900 mg; Cycle 4, Day 8: 1000 mg; Cycle 4, Day 15: 1000 mg; Cycles 5-9, Day 1: 1000 mg. | Drug | Nemtabrutinib with Venetoclax and Obinutuzumab |
Primary outcome
Undetectable MRD
Time frame: 15 months
This measure is the proportion of subjects with undetectable MRD at 10^-4 sensitivity level by flow cytometry after treatment with nemtabrutinib, venetoclax, and obinutuzumab for frontline management of CLL.
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 8 Jul 2026.
- Individual participant dataSharing planned: No
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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.
Medical College of Wisconsin Cancer Center Clinical Trials Office contact
Guru S Guru Murthy, MD principal investigator
Medical College of Wisconsin
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 Nemtabrutinib, Venetoclax and Obinutuzumab in people with Chronic Lymphocytic Leukemia, run by Medical College of Wisconsin 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 31 inclusion and 31 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: opening soon, as of the sponsor's last update on 8 Jul 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?
Contact Medical College of Wisconsin Cancer Center Clinical Trials Office (866-680-0505 ext. 8900, cccto@mcw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Undetectable MRD (time frame: 15 months). 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 8 Jul 2026.