AzTrials
AzTrials

Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaPhase 2NCT07194980

Nemtabrutinib and Lisocabtagene Maraleucel for the Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

A Phase 2 study testing Nemtabrutinib and Lisocabtagene Maraleucel in people with Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase II trial studies how well the addition of nemtabrutinib to lisocabtagene maraleucel in treating patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nemtabrutinib and Lisocabtagene Maraleucel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
1 Dec 2026to 20 Oct 2029
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

  • Confirmed diagnosis of CLL/SLL per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) classification
  • Measurable disease by imaging (lymph node [LN] > 1.5cm) or absolute lymphocyte count (ALC) (> 5000/μL) or marrow involvement of at least 30% by flow cytometry
  • Eligible for lisocabtagene maraleucel (liso-cel) as standard-of-care per Food and Drug Administration (FDA) label for CLL/SLL
  • At least 18 years of age at time of study enrollment
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • The ability to swallow and retain oral medication
Show all 24Show fewer
  • NOTE: Administration of nemtabrutinib is not permitted through a percutaneous endoscopic gastro-jejunal (J PEG) tube
  • Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
  • 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. Hepatitis B screening tests are not required unless:
  • Known history of HBV infection,
  • As mandated by local health authority
  • Absolute neutrophil count (ANC) ≥750/μL (or ≥500/μL in participants with documented bone marrow involvement)
  • Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
  • Hemoglobin ≥ 8 g/dL
  • Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
  • Platelets ≥50 000/μL (or ≥30 000/μL in participants with documented bone marrow involvement)
  • Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
  • Creatinine ≤ 1.5 × upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) ≥ 30 mL/min for participant with creatinine levels > 1.5 × institutional ULN
  • Creatinine clearance (CrCl) should be calculated per institutional standard
  • Total bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 × ULN
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 × ULN (≤ 5 × ULN for participants with liver metastases)
  • International normalized ratio (INR) OR prothrombin time (PT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Cardiac (echocardiogram [Echo] or multi-gated acquisition scan [MUGA]) ejection fraction ≥ 40%

Who cannot join

  • Diagnosis of Richter Transformation
  • Clinically significant (symptomatic) central nervous system (CNS) involvement at time of study enrollment. Previously treated CNS disease is allowed if the participant is asymptomatic. Incidental findings including positive cerebral spinal fluid (CSF) studies are not exclusionary
  • Active infection and uncontrolled infection
  • Active HBV/hepatitis C virus (HCV) infection
  • Participants must have completed curative anti-viral therapy for HCV at least 4 weeks prior to study enrollment
  • Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to study enrollment
Show all 36Show fewer
  • 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
  • HIV with a detectable viral load or a CD4 count ≤ 350 cells/µL at time of screening
  • Participants with HIV who do not meet the above criteria are eligible if they are on a stable antiretroviral therapy (ART) regimen (ART must not be strong CYP3A4 inducers) for at least 4 weeks prior to study entry and are compliant with ART are eligible
  • Patients with an AIDS defining opportunistic infection in the past 12 months prior to screening
  • Gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy)
  • 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
  • Corrected QT interval (QTc) prolongation (defined as a QTc > 450 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree atrioventricular (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
  • Known prior progressive disease while on nemtabrutinib
  • NOTE: Refer to the investigator's brochure (IB) for details regarding prior recipients of nemtabrutinib
  • History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding
  • Known additional malignancy that is progressing or has required active treatment within the past 2 years
  • NOTE: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Participants with low-risk, early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA < 10ng/mL), either treated with definitive intent or untreated in active surveillance with stable disease, are not excluded
  • A participant of childbearing potential (POCBP) who has a positive urine pregnancy test within 72 hours prior to study enrollment. 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 participant to start receiving study medication
  • Need or anticipation of need for additional bridging therapy in addition to nemtabrutinib
  • Palliative radiation therapy for less than 2 weeks or the use of prednisone 30mg (or the prednisone equivalent) for a maximum of 5 days is allowed and is not exclusionary
  • 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 a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of inactivated vaccines are allowed
  • 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
  • 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 a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Any condition or history that the study investigator deems not in the best interest of the patient to participate

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Fred Hutch Immunotherapy Intake contact

206-606-4668

immunotherapy@fredhutch.org

United States1 site, 1 recruiting

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    Fred Hutch Immunotherapy Intake, 206-606-4668, immunotherapy@fredhutch.org

    Jennifer Huang, MD, PhD

    Recruiting

Other trials in United States

About this study

Official title: Safety and Efficacy of the Addition of Nemtabrutinib to Lisocabtagene Maraleucel in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia

This phase II trial studies how well the addition of nemtabrutinib to lisocabtagene maraleucel in treating patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Nemtabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lisocabtagene maraleucel is a type of treatment called chimeric antigen receptor (CAR) T-cell therapy, in which a patient's T-cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T-cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T-cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T-cells are grown in the laboratory and given to the patient by infusion for treatment. Adding nemtabrutinib to lisocabtagene maraleucel may be an effective treatment for relapsed/refractory CLL/SLL.

Read the detailed description

OUTLINE:

Patients receive nemtabrutinib orally (PO) daily on days 1-28 of each cycle (NOTE: nemtabrutinib is not given during lymphodepleting therapy). Cycles repeat every 28 days for up to 1 year after lisocabtagene maraleucel infusion in the absence of disease progression or unacceptable toxicity. Patients undergo leukapheresis 7 days after start of nemtabrutinib treatment. Patients receive standard of care (SOC) lymphodepleting therapy consisting of cyclophosphamide intravenously (IV) and fludarabine IV on approximately the 5th, 4th, and 3rd day prior to lisocabtagene maraleucel infusion. Patients then receive lisocabtagene maraleucel IV 36-96 hours after completion of SOC lymphodepleting therapy. Patients also undergo transthoracic echocardiogram (TTE) or multigated acquisition scan (MUGA) during screening, and positron emission tomography (PET)/computed tomography (CT) scans, Bone marrow biopsy and aspiration, lymph node biopsy, and blood sample collection throughout the study.

After completion of study treatment, patients are followed for 5 years.

Being tested
Nemtabrutinib, Lisocabtagene Maraleucel
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.

  • NemtabrutinibDrug

    Also called ARQ 531, ARQ-531, ARQ531, Bruton's Tyrosine Kinase Inhibitor ARQ 531

    Given PO

  • Lisocabtagene MaraleucelBiological

    Also called Anti-CD19-CAR Genetically Engineered Autologous T Lymphocytes JCAR017, Anti-CD19-CAR Genetically Engineered Autologous T-lymphocytes JCAR017, Autologous Anti-CD19-EGFRt-4-1BB-zeta-modified CAR CD8+ and CD4+ T-lymphocytes JCAR017, Breyanzi

    Given IV

Study groups in NCT07194980
Study groupRoleWhat they receive
Treatment (nemtabrutinib, lisocabtagene maraleucel)ExperimentalPatients receive nemtabrutinib PO daily on days 1-28 of each cycle (NOTE: nemtabrutinib is not given during lymphodepleting therapy). Cycles repeat every 28 days for up to 1 year after lisocabtagene maraleucel infusion in the absence of disease progression or unacceptable toxicity. Patients undergo leukapheresis 7 days after start of nemtabrutinib treatment. Patients receive SOC lymphodepleting therapy consisting of cyclophosphamide IV and fludarabine IV on approximately the 5th, 4th, and 3rd day prior to lisocabtagene maraleucel infusion. Patients then receive lisocabtagene maraleucel IV 36-96 hours after completion of SOC lymphodepleting therapy. Patients also undergo TTE or MUGA during screening, and PET/CT scans, bone marrow biopsy and aspiration, lymph node biopsy, and blood sample collection throughout the study.
Receives: Drug: Nemtabrutinib; Biological: Lisocabtagene Maraleucel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete response (CR)

    Will be defined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. Binary proportions will be estimated along with 95% confidence intervals. Confidence intervals for binary proportions will be estimated using the Wilson Score method.

    Measured: Up to 5 years after completion of study treatment

Secondary outcomes (12)

  1. Overall response rate

    Will be defined by the iwCLL criteria. Binary proportions will be estimated along with 95% confidence intervals. Confidence intervals for binary proportions will be estimated using the Wilson Score method.

    Measured: Up to 5 years after completion of study treatment

  2. Overall survival (OS)

    The distribution of OS will be estimated using the method of Kaplan-Meier. Confidence intervals around median time will be estimated using the Brookmeyer Crowley method.

    Measured: From first dose of protocol treatment to documentation of the first sign of disease progression or death from any cause, assessed up to 5 years after completion of study treatment

  3. Progression free survival (PFS)

    Will be defined by the iwCLL criteria. The distribution of PFS will be estimated using the method of Kaplan-Meier. Confidence intervals around median time will be estimated using the Brookmeyer Crowley method.

    Measured: From first dose of protocol treatment to documentation of the first sign of disease progression or death from any cause, assessed up to 5 years after completion of study treatment

  4. Time to response (TTR)

    Will be defined by the iwCLL criteria among responders. The distribution of TTR will be estimated using the method of Kaplan-Meier. Confidence intervals around median time will be estimated using the Brookmeyer Crowley method.

    Measured: From start of protocol treatment to first documentation of response among participants documented to have a response, assessed up to 5 years after completion of study treatment

  5. Time to next treatment (TTNT)

    TTNT is only defined for participants who start a new treatment and only for those participants with progressive CLL/SLL. The distribution of TTNT will be estimated using the method of Kaplan-Meier. Confidence intervals around median time will be estimated using the Brookmeyer Crowley method.

    Measured: From start of protocol treatment to the start of a subsequent treatment, assessed up to 5 years after completion of study treatment

  6. Duration of response (DoR)

    Will be defined by the iwCLL criteria among responders. The distribution of DoR will be estimated using the method of Kaplan-Meier. Confidence intervals around median time will be estimated using the Brookmeyer Crowley method.

    Measured: From first documentation of response to documentation of the first sign of disease progression or death from any cause, whichever comes first, assessed up to 5 years after completion of study treatment

  7. CR on positron emission tomography/computed tomography by Lugano criteria

    Binary proportions will be estimated along with 95%. Confidence intervals. Confidence intervals for binary proportions will be estimated using the Wilson Score method.

    Measured: Up to 5 years after completion of study treatment

  8. Incidence of adverse events

    Will be assessed by Common Terminology Criteria for Adverse Events 5.0.

    Measured: Up to 30 days after the last dose of nemtabrutinib

  9. Incidence of dose-limiting toxicity (DLT)

    For the purpose of this study, the initial observed DLT will be considered the event which counts toward safety suspension rules.

    Measured: Up to 28 days following the infusion of lisocabtagene maraleucel

  10. Incidence of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity (ICANS)

    Grade, day of onset, and duration of CRS or ICANS by American Society of Transplant and Cellular Therapy (ASTCT) Consensus grading.

    Measured: Up to 30 days following the infusion of lisocabtagene maraleucel

  11. Time to CRS or ICANS onset

    Grade, day of onset, and duration of CRS or ICANS by ASTCT Consensus grading. The distribution of time to CRS or ICANS onset will be estimated using the method of Kaplan-Meier. Confidence intervals around median time will be estimated using the Brookmeyer Crowley method.

    Measured: Up to 30 days following the infusion of lisocabtagene maraleucel

  12. Time from CRS or ICANS onset to resolution

    Grade, day of onset, and duration of CRS or ICANS by ASTCT Consensus grading. The distribution of time from CRS or ICANS onset to resolution will be estimated using the method of Kaplan-Meier. Confidence intervals around median time will be estimated using the Brookmeyer Crowley method.

    Measured: Up to 30 days following the infusion of lisocabtagene maraleucel

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2025
  2. Study start1 Dec 2026 (estimated)
  3. Primary completion20 Oct 2029 (estimated)
  4. Study completion20 Oct 2029 (estimated)

Resources

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
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07194980
Sponsor's protocol ID
RG1125624
Other IDs
NCI-2025-06406, 20853
Status last verified
Sep 2026
First submitted
19 Sep 2025
Last updated
29 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nemtabrutinib and Lisocabtagene Maraleucel in people with Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by Fred Hutchinson Cancer Center 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 24 inclusion and 36 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: looking for participants now, as of the sponsor's last update on 29 Oct 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 Fred Hutch Immunotherapy Intake (206-606-4668, immunotherapy@fredhutch.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete response (CR) (time frame: Up to 5 years after completion of study treatment). 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 NCT07194980.

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 29 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in