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

Plain English Summary

Nemtabrutinib and Lisocabtagene Maraleucel for the Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma is a Phase 2 clinical trial sponsored by Fred Hutchinson Cancer Center studying Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. This trial tests a new combination of two treatments, nemtabrutinib and lisocabtagene maraleucel, for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that has returned or not responded to previous treatments. It is for adults diagnosed with relapsed or refractory CLL/SLL who meet specific health and disease criteria. Participants will receive both oral nemtabrutinib and an infusion of lisocabtagene maraleucel (a type of CAR T-cell therapy). Alternative treatments may include other chemotherapy, targeted therapies, or stem cell transplants, depending on the patient's specific situation and prior treatments. The trial aims to enroll 20 participants.

Official 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). 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with a confirmed diagnosis of CLL/SLL. Patients whose disease has returned after treatment or has not responded to prior therapies. Individuals with measurable disease, good general health (ECOG performance status 0-2), and adequate blood counts and organ function. Patients with a history of Hepatitis B infection may be eligible if on antiviral therapy with undetectable viral load, but active Hepatitis B or C infection is generally excluded. This trial is studying Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how many patients achieve a complete response, meaning no detectable signs of cancer, which indicates a significant positive effect of the treatment. The specific primary outcome measures are: Complete response (CR) (Up to 5 years after completion of study treatment). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for more effective treatments for patients with CLL/SLL that has become resistant to existing therapies, potentially offering a new option where current treatments Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, where improved treatment options are needed.

Investor Insight

This trial targets a specific subset of blood cancer patients, indicating a focus on personalized medicine within the growing field of CAR T-cell therapies and targeted agents, with potential for impr Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for you, considering your specific type of CLL/SLL and previous treatments. Participation involves receiving oral nemtabrutinib and an infusion of lisocabtagene maraleucel, with regular monitoring and follow-up appointments. Be prepared for potential side effects and discuss any concerns about swallowing pills or the infusion process with your medical team. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 20 participants

Interventions

• DRUG: Nemtabrutinib — Given PO
• BIOLOGICAL: Lisocabtagene Maraleucel — Given IV

Primary Outcomes

• Complete response (CR) (Up to 5 years after completion of study treatment)

Secondary Outcomes

• Overall response rate (Up to 5 years after completion of study treatment)
• Overall survival (OS) (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)
• Progression free survival (PFS) (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)
• Time to response (TTR) (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)
• Time to next treatment (TTNT) (From start of protocol treatment to the start of a subsequent treatment, assessed up to 5 years after completion of study treatment)

Full Eligibility Criteria

Inclusion Criteria:

* 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

  * 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) ≥ 500/µL

  * Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
  * No lower limit if cytopenia is related to bone marrow involvement
* Hemoglobin ≥ 8 g/dL

  * Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
  * No lower limit if cytopenia is related to bone marrow involvement
* Platelets ≥ 25 000/µL

  * Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
  * No lower limit if cytopenia is related to bone marrow involvement
* 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%

Exclusion Criteria:

* 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
  * 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 

Trial Locations

• Fred Hutch/University of Washington Cancer Consortium, Seattle, Washington, United States

Frequently Asked Questions

Related Conditions

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma
• B-cell Lymphoma
• Hematologic Malignancies
• Relapsed Cancer
• Refractory Cancer
• CAR T-cell Therapy
• Targeted Cancer Therapy
• Oncology
• Immunotherapy

More Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Trials

View all Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma clinical trials